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1.
J Xray Sci Technol ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32224536

RESUMO

OBJECTIVE: To elevate safety and efficacy of en bloc transurethral resection with 980 nm laser as treatment for primary non-muscle-invasive bladder cancer (NMIBC). METHODS: Total 84 cases were enrolled in this study. Among them, 36 and 48 cases underwent treatment using the 980 nm laser and the traditional TUR-BT procedure, respectively. The peri-operative characteristics (tumor size, tumor multiplicity, tumor grade, etc.) and intra-operative complications (obturator nerve reflex, bladder perforation, bladder irrigation, etc.) were recorded and compared between the two groups. RESULTS: There are no significant difference in baseline characteristics between laser and TUR-Bt treatment groups. Operation time also has no significant difference in two groups. Obturator nerve reflex and bladder perforation were noted in 6 patients and in 3 patients during TUR-Bt group, respectively. No obturator nerve reflex and bladder perforation were observed in the laser group. The patients who need bladder irrigation was lower in laser group than in TUR-Bt group. There were no significant differences in catheterization time and hospitalization time between two groups. No significant difference in the overall recurrence rate were observed among the two groups during the follow-up periods. CONCLUSION: En bloc transurethral resection using 980 nm laser is an effective and safe treatment option for non-muscle-invasive bladder cancer. Compared to the traditional TUR-Bt procedure, the procedure using 980 nm laser has fewer perioperative complications and similar oncological results.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32124474

RESUMO

Cancer stem cells have been identified as the major cause of cancer initiation and progression. To investigate the effects of puerarin 6″-O-xyloside (PXY), derived from Pueraria lobata (Willd.) Ohwi, on lung cancer stem cells, we enriched and identified a subpopulation of lung cancer stem-like cells (LCSLCs) derived from lung adenocarcinoma A549 cells with traits including high self-renewal and invasive capability in vitro, elevated tumorigenicity in vivo, and high expression of stem cell markers CD44, CD133 and aldehyde dehydrogenase 1 (ALDH1). We found that PXY could impair cell viability, suppress self-renewal and invasive capability, and decrease CD133, CD44 and ALDH1 mRNA expression in LCSLCs in a dose-dependent manner. Furthermore, we showed that PXY suppressed the self-renewal and invasive capability of LCSLCs at least in part through suppressing the activation of Akt/c-Myc signalling. In conclusion, PXY can block the traits of LCSLCs, indicating that PXY may be a candidate compound for lung adenocarcinoma therapy via eliminating LCSLCs.

4.
J Contam Hydrol ; 231: 103620, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32126294

RESUMO

Surfactant solutions have been frequently studied for soil remediation. However, since they are expensive, massive consumption of surfactant solution can constrain their application. Surfactant microbubbles, or colloidal gas aphrons (CGAs), can serve as cost effective alternatives of surfactant solution because the use of CGAs reduce the amount of surfactant consumption. Moreover, CGAs can also improve the contact with the contaminated environment due to their unique surface properties, e.g. containing 40-70% of gas, small size, large interfacial areas, water-like flow properties and buoyant rise velocities. In this review paper, the properties and flow character of CGAs in soil matrix reviewed due to their relevance to soil remediation process. A comprehensive overview of the application of CGAs in flushing off organic pollutants and heavy metals, and carrying oxygen, bacteria and dissolved materials for soil remediation were provided. This paper also highlighted the limitation of CGAs application and important future research scopes.

5.
ACS Chem Neurosci ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32203651

RESUMO

Prenatal stress (PNS) has a prolonged and adverse effect on offspring, leading to a significantly increased vulnerability to developing depression in their later life. Traditional therapies have delayed onset and limited efficacy; thus, it remains an urgent need to find novel medications with fast-onset and high-efficacy potentials. Crocin, with its structure clearly examined, has shown antidepressant-like effects. However, few studies extensively investigated its effect especially in mice exposed to PNS. Using an established PNS model, we tested whether crocin could have a rapid and persistent antidepressant-like effect in PNS mice. Growth hormone secretagogue receptor (GHSR) and phosphoinositide 3-kinase (PI3K) inhibitors were used to test their effects in antidepressant-like effect of crocin. Hippocampal GHSR-PI3K signaling was examined both in PNS mice treated with a single dose of crocin and in combination of GHSR inhibitor. PNS mice showed depression-like behaviors at juvenile and adulthood, and crocin induced an instant and persistent antidepressant-like response in PNS mice in a dose-dependent manner. Moreover, crocin increased the expression of hippocampal synaptic plasticity-associated proteins through the restoration of GHSR-PI3K signaling. Inhibitions of both GHSR and PI3K abolished the effect of crocin in alleviating depressive-like behaviors. More importantly, GHSR inhibitor JMV2959 blocked the enhanced expression of hippocampal plasticity-related proteins induced by crocin. The present study demonstrated that crocin induced a fast-onset and prolonged antidepressant effect in PNS mice and suggested that GHSR-PI3K signaling may play a key role in crocin's effect at least partially by a restoration of hippocampal synaptic plasticity-associated proteins.

6.
BMC Infect Dis ; 20(1): 168, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087697

RESUMO

BACKGROUND: Respiratory tract infection (RTI) in young children is a leading cause of morbidity and hospitalization worldwide. There are few studies assessing the performance for bronchoalveolar lavage fluid (BALF) versus oropharyngeal swab (OPS) specimens in microbiological findings for children with RTI. The primary purpose of this study was to compare the detection rates of OPS and paired BALF in detecting key respiratory pathogens using suspension microarray. METHODS: We collected paired OPS and BALF specimens from 76 hospitalized children with respiratory illness. The samples were tested simultaneously for 8 respiratory viruses and 5 bacteria by suspension microarray. RESULTS: Of 76 paired specimens, 62 patients (81.6%) had at least one pathogen. BALF and OPS identified respiratory pathogen infections in 57 (75%) and 49 (64.5%) patients, respectively (P > 0.05). The etiology analysis revealed that viruses were responsible for 53.7% of the patients, whereas bacteria accounted for 32.9% and Mycoplasma pneumoniae for 13.4%. The leading 5 pathogens identified were respiratory syncytial virus, Streptococcus pneumoniaee, Haemophilus influenzae, Mycoplasma pneumoniae and adenovirus, and they accounted for 74.2% of etiological fraction. For detection of any pathogen, the overall detection rate of BALF (81%) was marginally higher than that (69%) of OPS (p = 0.046). The differences in the frequency distribution and sensitivity for most pathogens detected by two sampling methods were not statistically significant. CONCLUSIONS: In this study, BALF and OPS had similar microbiological yields. Our results indicated the clinical value of OPS testing in pediatric patients with respiratory illness.

7.
Nano Lett ; 20(3): 1637-1646, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32013452

RESUMO

Nanotechnology-based RNA interference (RNAi) has shown great promise in overcoming the limitations of traditional clinical treatments for glioblastoma (GBM). However, because of the complexity of brain physiology, simple blood-brain barrier (BBB) penetration or tumor-targeting strategies cannot entirely meet the demanding requirements of different therapeutic delivery stages. Herein, we developed a charge conversional biomimetic nanoplatform with a three-layer core-shell structure to programmatically overcome persistent obstacles in siRNA delivery to GBM. The resulting nanocomplex presents good biocompatibility, prolonged blood circulation, high BBB transcytosis, effective tumor accumulation, and specific uptake by tumor cells in the brain. Moreover, red blood cell membrane (RBCm) disruption and effective siRNA release can be further triggered elegantly by charge conversion from negative to positive in the endo/lysosome (pH 5.0-6.5) of tumor cells, leading to highly potent target-gene silencing with a strong anti-GBM effect. Our study provides an intelligent biomimetic nanoplatform tailored for systemically siRNA delivery to GBM, leveraging Angiopep-2 peptide-modified, immune-free RBCm and charge conversional components. Improved therapeutic efficacy, higher survival rates, and minimized systemic side effects were achieved in orthotopic U87MG-luc human glioblastoma tumor-bearing nude mice.

8.
Environ Pollut ; 260: 114014, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-32000026

RESUMO

Microbial degradation is an important pathway for the attenuation of polybrominated diphenyl ethers (PBDEs) in natural soils. In this study, the compound-specific stable isotope analysis (CSIA) was applied to characterize microbial degradation of BDE-153, one of the prevailing and toxic PBDE congeners, in natural wetland soils. During the 45-day incubation, the residual percentages of BDE-153 decreased to 67.9% and 73.6% in non-sterilized soils spiked with 1.0 and 5.0 µg/g, respectively, which were both much lower than those in sterilized soils (96.0% and 97.2%). This result indicated that microbial degradation could accelerate BDE-153 elimination in wetland soils. Meanwhile, the significant carbon isotope fractionation was observed in non-sterilized soils, with δ13C of BDE-153 shifting from -29.4‰ to -26.7‰ for 1.0 µg/g and to -27.2‰ for 5.0 µg/g, respectively, whilst not in sterilized soils. This phenomenon indicated microbial degradation could induce stable carbon isotope fractionation of BDE-153. The carbon isotope enrichment factor (εc) for BDE-153 microbial degradation was first determined as -7.58‰, which could be used to assess the microbial degradation and bioavailability of BDE-153 in wetland soils. Based on δ13C and εc, the new methods were developed to dynamically and quantitatively estimate degradation degree and bioavailability of BDE-153 during degradation process, respectively, which could exclude interference of physical processes. This work revealed that CSIA was a promising method to investigate in situ microbial degradation of PBDEs in field studies.

9.
Biomaterials ; 234: 119760, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945619

RESUMO

Combination therapy has been developed as an innovative modality for effective cancer therapy. However, the administration of combinatorial therapeutics is limited by the varying pharmacokinetics of different drugs. Although numerous nanoparticles (NPs) can synchronize the delivery of combinatorial therapeutics to tumor cells, their clinical translation is still challenged, which is partly due to the complexity to precisely control the loading of combinatorial therapeutics to maximize therapeutic efficacy and suboptimal NP properties. Herein, a new redox-responsive polyprodrug nanoplatform was developed for targeted siRNA delivery and synergistic cancer therapy. This NP platform is made with redox-responsive 10-hydroxycamptothecin (HCPT)-based polyprodrug (polyHCPT) as the inner core, amphiphilic lipid-poly (ethylene glycol) (lipid-PEG) as the outer shell, and lactobionic acid (LA) decoration on the surface. After siRNA loading and subsequent systemic administration, the resulting NP platform could accumulate in tumor tissues and target hepatoma cells via specific recognition between LA and asialoglycoprotein (ASGP) receptors. With the high concentration of glutathione (GSH) in the cytoplasm to break the disulfide bonds in the polyHCPT, intact HCPT molecules and encapsulated B-cell lymphoma 2 (Bcl-2) siRNA (siBcl-2) could be rapidly released, leading to the synergistic inhibition of tumor growth via the induction of apoptosis by HCPT and the concurrent silencing of the anti-apoptotic gene by siBcl-2.

10.
Epilepsy Behav ; 102: 106589, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726317

RESUMO

Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with depression. But, up to date, the association of BR alterations in TCS with depression in patients with epilepsy has never been reported. This study was to investigate the possible role of BR examination via TCS in patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-TCS) and depression. Forty-six patients with IGE-TCS and 45 healthy controls were recruited. Echogenicity of the caudate nuclei (CN), lentiform nuclei (LN), substantia nigra (SN), and BR and widths of the lateral ventricle (LV) frontal horns and the third ventricle (TV) were assessed via TCS. The determination of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), and depression severity measured by Chinese version Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and Beck Depression Inventory-II (BDI-II). The width of TV in patients with epilepsy was found significantly larger than that in healthy controls (p = 0.001), but there was no significant difference in TV width between patients with IGE-TCS with and without depression. There were no significant differences between patients with IGE-TCS and healthy controls in LV frontal horn width, as well as in SN, CN, LN, and BR echogenicity. Here, it seems that patients with IGE-TCS were detected with smaller SN echogenic area compared with controls though they had no statistical significance. Patients with IGE-TCS with hypoechogenic BR had significantly higher C-NDDI-E and BDI-II scores than those with normal BR signal, and most patients with IGE-TCS with depression exhibited hypoechogenic BR, but few patients with IGE-TCS without depression exhibited hypoechogenic BR. In conclusion, BR echogenic signal alterations in TCS can be a biomarker for depression in epilepsy, but it might not be associated with epilepsy itself. The alterations of SN echogenic area and TV width in TCS may reflect a potential role of SN and diencephalon structure in the pathogenesis of epilepsy, which needs to be further elucidated.

11.
Parasitol Res ; 119(1): 105-114, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31773309

RESUMO

The protistan pathogens Cryptosporidium and Enterocytozoon bieneusi can cause significant intestinal diseases in animals and humans. However, limited information is available regarding prevalence and molecular characterization of Cryptosporidium and E. bieneusi in ruminants in Northern China. In this study, the overall prevalence of Cryptosporidium and E. bieneusi was 19.3% (62/321) and 28.97% (93/321) in dairy calves and 1.10% (9/818) and 13.57% (111/818) in sika deer (Cervus nippon) in four provinces in Northern China, respectively. The prevalence of Cryptosporidium and E. bieneusi in different factor groups was various. Five Cryptosporidium species/genotypes were identified, of which C. parvum, C. ryanae, C. bovis, and C. andersoni were only found in dairy calves, and only Cryptosporidium deer genotype was found in sika deer. Moreover, J, I, and BEB4 ITS genotypes of E. bieneusi were found in dairy calves, and six known genotypes (JLD-III, JLD-IX, JLD-VII, EbpC, BEB6, and I) and ten novel genotypes (namely LND-I and JLD-XV to JLD-XXIII) were found in sika deer in this study. Cryptosporidium parvum and E. bieneusi genotype J were identified as the predominant species/genotypes in dairy calves, whereas the predominance of Cryptosporidium spp. and E. bieneusi in sika deer was Cryptosporidium deer genotype and BEB6, respectively. The present study reported the prevalence and genotypes of Cryptosporidium and E. bieneusi in dairy calves and sika deer in four provinces in northern China. The present findings also suggest that investigated dairy calves and sika deer may play an important role in the transmission of E. bieneusi and Cryptosporidium to humans and other animals, and also in an effort to better understand the epidemiology of these enteric pathogens in China.

12.
IEEE Trans Cybern ; 50(2): 835-845, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30346303

RESUMO

Many well-known first-order gradient methods have been extended to cope with large-scale composite problems, which often arise as a regularized empirical risk minimization in machine learning. However, their optimal convergence is attained only in terms of the weighted average of past iterative solutions. How to make the individual convergence of stochastic gradient descent (SGD) optimal, especially for strongly convex problems has now become a challenging problem in the machine learning community. On the other hand, Nesterov's recent weighted averaging strategy succeeds in achieving the optimal individual convergence of dual averaging (DA) but it fails in the basic mirror descent (MD). In this paper, a new primal averaging (PA) gradient operation step is presented, in which the gradient evaluation is imposed on the weighted average of all past iterative solutions. We prove that simply modifying the gradient operation step in MD by PA strategy suffices to recover the optimal individual rate for general convex problems. Along this line, the optimal individual rate of convergence for strongly convex problems can also be achieved by imposing the strong convexity on the gradient operation step. Furthermore, we extend PA-MD to solve regularized nonsmooth learning problems in the stochastic setting, which reveals that PA strategy is a simple yet effective extra step toward the optimal individual convergence of SGD. Several real experiments on sparse learning and SVM problems verify the correctness of our theoretical analysis.

13.
J Environ Manage ; 253: 109751, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675594

RESUMO

Using 2025 as the target year, we quantitatively assessed the reduction potentials of emissions of primary pollutants (including CO, HC, NOx, PM2.5 and PM10) under different vehicle control policies and the impacts of vehicle emission control policies in the BTH region on the regional PM2.5 concentration in winter and the surface ozone (O3) concentration in summer. Comparing the different scenarios, we found that (1) vehicle control policies will bring significant reductions in the emissions of primary pollutants. Among the individual policies, upgrading new vehicle emission standards and fuel quality in Beijing, Tianjin, and Hebei will be the most effective policy, with emission reductions of primary pollutants of 26.3%-54.7%, 38.0%-70.3% and 46.0%-81.6% in 2025, respectively; (2) for PM2.5 in winter, the Combined Scenario (CS) will lead to a reduction of 0.5-3.9 µg m-3 (3.5%-11.6%) for the monthly average PM2.5 concentrations in most areas. The monthly nitrate and ammonium concentrations would reduce by 5.8% and 5.3%, respectively, in the whole BTH region, indicating that vehicle emission control policies may play an important role in the reduction of PM2.5 concentrations in winter, especially for nitrate aerosols; and (3) for O3 concentrations in summer, vehicle emission control policies will lead to significant decreases. Under the CS scenario, the maximum reduction of monthly average O3 concentrations in the summer is approximately 3.6 ppb (5.9%). Most areas in the BTH region have a decrease of 15 ppb (7.5%) in peak values compared to the base scenario. However, in some VOC-sensitive areas in the BTH region, such as the southern urban areas, significant reductions in NOx may lead to increases in ozone concentrations. Our results highlight that season- and location-specific vehicle emission control measures are needed to alleviate ambient PM2.5 and O3 pollution effectively in this region due to the complex meteorological conditions and atmospheric chemical reactions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Pequim , China , Monitoramento Ambiental , Material Particulado , Emissões de Veículos
14.
J Nanosci Nanotechnol ; 20(3): 1723-1731, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492336

RESUMO

Hydroxyapatite nanorod-supported metallic Cu0 nanoparticle catalysts (Cux/HAP) were prepared by the wetness chemical reduction method. The metallic Cu0 nanoparticles were well dispersed on the surfaces of the HAP nanorods. The alkaline HAP nanorods inhibited the crystal growth of the metallic Cu0 nanoparticles. The HAP nanorods also retarded the oxidation of the metallic Cu0 nanoparticles. The Cux/HAP catalyst exhibited a higher catalytic activity for the oxidation of 1,2-propanediol with gaseous oxygen to lactic, acetic, and formic acids with the total selectivity of 70.3% even at a lower reaction temperature of 140 °C. The total selectivity of lactic, acetic, and formic acids reached 93.1% at a mild reaction temperature of 180 °C. However, the sole monometallic Cu0 nanoparticles or HAP nanorods had no catalytic activity for the oxidation of 1,2-propanediol. The metallic Cu0 nanoparticles and alkaline HAP nanorods in the Cux/HAP catalyst synergistically catalyzed the oxidation of 1,2-propanediol to carboxylic acid.

15.
Onco Targets Ther ; 12: 8841-8851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802897

RESUMO

Purpose: In previous studies, we confirmed that the overexpression of lncRNA NORAD was associated with the occurrence and development of gastric cancer (GC). The aim of the present study was to explore the molecular mechanism of lncRNA NORAD on GC cell proliferation and apoptosis in vitro and in vivo. Patients and methods: The quantitative Real-Time PCR (qRT-PCR) was used to determine the expression levels of lncRNA NORAD and miR-214 in GC tissues and cells. The interaction between lncRNA NORAD and miR-214 was investigated by biological information and Dual-Luciferase gene reporter assay. Effect of lncRNA NORAD on GC tumor growth in vivo was studied in tumor xenograft model mice. The apoptosis of GC cells was determined by flow cytometry. The proliferation of GC cells was determined by 5-ethynyl-2´-deoxyuridine (EDU) and colony formation assays. Western Blot was used to determine the expressions of caspase-3, Akt and mTOR in GC tissues and cells. Results: The qRT-PCR results showed that lncRNA NORAD was highly expressed in human GC tissues and cell lines, while miR-214 was significantly down-regulated. Meanwhile, there was a direct interaction between lncRNA NORAD and miR-214. In addition, lncRNA NORAD could promote the growth and proliferation of GC cells both in vivo and in vitro. NOARD could also inhibit the apoptosis of GC cells by down-regulating caspase-3; however, miR-214 overexpression attenuated this effect. Moreover, lncRNA NORAD promoted the phosphorylation of Akt and mTOR in mouse GC tissues and GC cell lines, while miR-214 mimics inhibited that promotion. Conclusion: These results suggested that NORAD could promote the development of GC by inhibiting miR-214 expression and activating the Akt/mTOR signaling pathway.

16.
Anticancer Res ; 39(12): 6523-6529, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810917

RESUMO

BACKGROUND/AIM: Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk. MATERIALS AND METHODS: A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location. CONCLUSION: MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.


Assuntos
Neoplasias Colorretais/genética , Metaloproteinase 9 da Matriz/genética , Metástase Neoplásica/genética , Polimorfismo de Nucleotídeo Único , Índice de Massa Corporal , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Regiões Promotoras Genéticas , Taiwan
17.
PLoS One ; 14(12): e0226175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830080

RESUMO

Mild cognitive impairment (MCI) is a heterogeneous cognitive disorder that is often comorbid with Parkinson's diseases (PD). The amnestic subtype of PD-MCI (PD-aMCI) has a higher risk to develop dementia. However, there is a lack of studies on the white matter (WM) structural changes of PD-aMCI. We characterized the WM structural changes of PD-aMCI (n = 17) with cognitively normal PD (PD-CN, n = 19) and normal controls (n = 20), using voxel-based and tract-based spatial statistics (TBSS) analyses on fractional anisotropy (FA) axial diffusivity (AD), and radial diffusivity (RD). By excluding and then including the motor performance as a covariate in the comparison analysis between PD-aMCI and PD-CN, we attempted to discern the influences of two neuropathological mechanisms on the WM structural changes of PD-aMCI. The correlation analyses between memory and voxel-based WM measures in all PD patients were also performed (n = 36). The results showed that PD-aMCI had smaller FA values than PD-CN in the diffuse WM areas, and PD-CN had higher AD and RD values than normal controls in the right caudate. Most FA difference between PD-aMCI and PD-CN could be weakened by the motor adjustment. The FA differences between PD-aMCI and PD-CN were largely spatially overlapped with the memory-correlated FA values. Our findings demonstrated that the WM structural differences between PD-aMCI and PD-CN were mainly memory-related, and the influence of motor adjustment might indicate a common mechanism underlying both motor and memory impairment in PD-aMCI, possibly reflecting a predominant influence of dopaminergic neuropathology.

18.
Drug Des Devel Ther ; 13: 4021-4033, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819373

RESUMO

Aim: The aim of this study was to characterize curcumin (CUR)-loaded CD133 aptamer A15 liposomes for their antitumor activity in vitro and in vivo. Methods: The modified CUR liposomes were prepared by the thin-film hydration technique. Results: The particles showed spherical shape under electron microscopy with sizes <100 nm. Initial drug burst release was observed within 2 hrs and then the drug was continuously released over 48 hrs. No aggregation or precipitation of liposomes was observed during storage for 3 months. In vitro results showed that blank LPs had lower cellular cytotoxicity. Both liposomes of CUR (with or without A15 modified) exhibited a similar trend of cellular cytotoxicity at the same concentration. With the extension of incubation time, A15-CUR LPs showed a greater inhibitory effect on cells. Cell internalization in DU145 cells was higher for A15-CUR LPs than others. An in vivo study using DU145 prostate carcinoma bearing mice showed that A15-CUR LPs reduced tumor growth more than other forms of CUR. Conclusion: These results indicate that A15 modified CUR liposomes are a promising candidate for antitumor drug delivery.

19.
Sci Transl Med ; 11(523)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852795

RESUMO

Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers, for example, in ~36% of hepatocellular carcinomas (HCCs) and ~68% of non-small cell lung cancers (NSCLCs). Current methods for restoration of p53 expression, including small molecules and DNA therapies, have yielded progressive success, but each has formidable drawbacks. Here, a redox-responsive nanoparticle (NP) platform is engineered for effective delivery of p53-encoding synthetic messenger RNA (mRNA). We demonstrate that the synthetic p53-mRNA NPs markedly delay the growth of p53-null HCC and NSCLC cells by inducing cell cycle arrest and apoptosis. We also reveal that p53 restoration markedly improves the sensitivity of these tumor cells to everolimus, a mammalian target of rapamycin (mTOR) inhibitor that failed to show clinical benefits in advanced HCC and NSCLC. Moreover, cotargeting of tumor-suppressing p53 and tumorigenic mTOR signaling pathways results in marked antitumor effects in vitro and in multiple animal models of HCC and NSCLC. Our findings indicate that restoration of tumor suppressors by the synthetic mRNA NP delivery strategy could be combined together with other therapies for potent combinatorial cancer treatment.

20.
Polymers (Basel) ; 11(11)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731476

RESUMO

In this study, a novel biobased poly(ethylene brassylate)-poly(furfuryl glycidyl ether) copolymer (PEBF) copolymer was synthesized and applied as a structure-directing template to incorporate graphene and 1,1'-(methylenedi-4,1-phenylene)bismaleimide (BMI) to fabricate a series of self-healing organic/inorganic hybrid materials. This ternary material system provided different types of diene/dienophile pairs from the furan/maleimide, graphene/furan, and graphene/maleimide combinations to build a crosslinked network via multiple Diels-Alder (DA) reactions and synergistically co-assembled graphene sheets into the polymeric matrix with a uniform dispersibility. The PEBF/graphene/BMI hybrid system possessed an efficient self-repairability for healing structural defects and an electromagnetic interference shielding ability in the Ku-band frequency range. We believe that the development of the biobased self-healing hybrid system provides a promising direction for the creation of a new class of materials with the advantages of environmental friendliness as well as durability, and shows potential for use in advanced electromagnetic applications.

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