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1.
Environ Health Prev Med ; 26(1): 20, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573606

RESUMO

BACKGROUND: Mounting evidence implicates an association between ambient air pollution and impaired reproductive potential of human. Our study aimed to assess the association between air pollution and ovarian reserve in young, infertile women. METHODS: Our study included 2276 Korean women who attended a single fertility center in 2016-2018. Women's exposure to air pollution was assessed using concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) that had been collected at 269 air quality monitoring sites. Exposure estimates were computed for 1, 3, 6, and 12 months prior to the ovarian reserve tests. Anti-Müllerian hormone (AMH) ratio (defined as an observed-to-expected AMH based on age) and low AMH (defined as < 0.5 ng/mL) were employed as indicators of ovarian reserve. We included a clustering effect of 177 districts in generalized estimating equations approach. A secondary analysis was conducted restricting the analyses to Seoul residents to examine the association in highly urbanized setting. RESULTS: The mean age was 36.6 ± 4.2 years and AMH level was 3.3 ± 3.1 ng/mL in the study population. Average AMH ratio was 0.8 ± 0.7 and low AMH was observed in 10.3% of women (n=235). The average concentration of six air pollutants was not different between the normal ovarian reserve and low AMH groups for all averaging periods. In multivariable models, an interquartile range (IQR)-increase in 1 month-average PM10 was associated with decrease in AMH ratio among total population (ß= -0.06, 95% confidence interval: -0.11, 0.00). When we restrict our analysis to those living in Seoul, IQR-increases in 1 and 12 month-average PM2.5 were associated with 3% (95% CI: -0.07, 0.00) and 10% (95% CI: -0.18, -0.01) decrease in AMH ratio. The ORs per IQR increase in the six air pollutants were close to null in total population and Seoul residents. CONCLUSIONS: In a cohort of infertile Korean women, there was a suggestive evidence of the negative association between ambient PM concentration and ovarian reserve, highlighting the potential adverse impact of air pollution on women's fertility.

2.
Adv Mater ; : e2007431, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33604974

RESUMO

A thermally stable perovskite solar cell (PSC) based on a new molecular hole transporter (MHT) of 1,3-bis(5-(4-(bis(4-methoxyphenyl) amino)phenyl)thieno[3,2-b]thiophen-2-yl)-5-octyl-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione (coded HL38) is reported. Hole mobility of 1.36 × 10-3 cm2 V-1 s-1 and glass transition temperature of 92.2 °C are determined for the HL38 doped with lithium bis(trifluoromethanesulfonyl)imide and 4-tert-butylpyridine as additives. Interface engineering with 2-(2-aminoethyl)thiophene hydroiodide (2-TEAI) between the perovskite and the HL38 improves the power conversion efficiency (PCE) from 19.60% (untreated) to 21.98%, and this champion PCE is even higher than that of the additive-containing 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-MeOTAD)-based device (21.15%). Thermal stability testing at 85 °C for over 1000 h shows that the HL38-based PSC retains 85.9% of the initial PCE, while the spiro-MeOTAD-based PSC degrades unrecoverably from 21.1% to 5.8%. Time-of-flight secondary-ion mass spectrometry studies combined with Fourier transform infrared spectroscopy reveal that HL38 shows lower lithium ion diffusivity than spiro-MeOTAD due to a strong complexation of the Li+ with HL38, which is responsible for the higher degree of thermal stability. This work delivers an important message that capturing mobile Li+ in a hole-transporting layer is critical in designing novel MHTs for improving the thermal stability of PSCs. In addition, it also highlights the impact of interface design on non-conventional MHTs.

3.
Eur J Cancer ; 144: 49-60, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338727

RESUMO

BACKGROUND: The most effective agent for the third-line treatment of advanced/metastatic gastric cancer (AGC) has not yet been determined. The aim of this network meta-analysis is to compare the relative efficacy and tolerability of third-line treatments for AGC. MATERIALS AND METHODS: We conducted a comprehensive literature review of randomised clinical trials (RCTs) using four electronic databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) were used as efficacy or tolerability outcomes. A Bayesian network meta-analysis with a random-effects model was used. RESULTS: Seven RCTs involving 2601 patients and nine treatments were included. The results suggested that 1 mg/kg nivolumab (nivolumab1) + 3 mg/kg ipilimumab (ipilimumab3) (hazard ratio [HR] 0.59, 95% credible interval [Crl] 0.38-0.91) was the most effective treatment, followed by nivolumab (HR 0.63, 95% Crl 0.50-0.79), for prolonging OS. Regorafenib (HR 0.40, 95% Crl 0.28-0.58) was most likely to improve PFS, followed by apatinib (HR 0.45, 95% Crl 0.33-0.60). Nivolumab1 + ipilimumab3 and nivolumab were better at improving ORR, whereas nivolumab1 + ipilimumab3 had the highest toxicity based on the AEs. For benefit-risk ratio, nivolumab, apatinib or regorafenib appeared to be the best options. Chemotherapy or two different dose combinations of nivolumab and ipilimumab were ranked as the next options because of poor tolerability, despite good efficacy. CONCLUSION: Immunotherapy (nivolumab) or antiangiogenic agents (regorafenib and apatinib) are associated with benefits for benefit-risk ratio as third-line monotherapy. This study might serve as a guideline to aid in the selection of third-line treatments for AGC.

4.
J Mater Chem B ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33289751

RESUMO

The endoplasmic reticulum (ER) apparatus is a part of the secretory pathway that transports proteins to the plasma membrane through vesicle trafficking, enabling post-translational modification of the newly synthesized proteins. Several diseases such as inflammation, neurodegenerative disorder, and bipolar disorder are closely associated with dysfunction of the ER stress response. Herein, we present an ER-targeting, intracellular delivery approach that utilized cell-penetrating peptide (CPP)-conjugated lipid/polymer hybrid nanovehicles (LPNVs). For this, we patched Penetratin, a type of CPP, onto the LPNVs with vesicular membranes formulated with poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). We found that the Penetratin-conjugated LPNV (LPNVPnt) was readily taken up by cells and showed specific ER-targeting ability, which was comparable to that of LPNVs conjugated with other types of CPPs. Moreover, we observed that remarkable lysosomal escape of the LPNVs occurred due to effective pH buffering with the aid of PEO-b-PCL-b-PEO. These results highlighted that our LPNVPnt system could pave the way for the development of an elaborate drug delivery technology for ER-targeting at the intracellular level.

5.
PLoS One ; 15(11): e0240689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33147280

RESUMO

With increased population and urban development, there are growing concerns regarding health impacts of environmental noise. We assessed the relationship between nighttime environmental noise and semen quality of men who visited for fertility evaluation. This is a retrospective cohort study of 1,972 male patient who had undertaken semen analysis between 2016-2018 at a single fertility center of Seoul, South Korea. We used environmental noise data of National Noise Information System (NNIS), Korea. Using semiannual nighttime noise measurement closest to the time of semen sampling, individual noise exposures at each patient's geocoded address were estimated with empirical Bayesian kriging method. We explored the association between environmental noise and semen quality indicators (volume, concentration, % of progressive motility, vitality, normal morphology, total motile sperm count, oligozoospermia, asthenozoospermia, and severe teratozoospermia) using multivariable regression and generalized additive models. Estimated exposure to nighttime environmental noise level in the study population was 58.3±2.2 Leq. Prevalence of oligozoospermia, asthenozoospermia, and severe teratozoospermia were 3.3%, 14.0%, and 10.1%. Highest quartile nighttime noise was associated with 3.5 times higher odds of oligozoospermia (95% CI: 1.18, 10.17) compared to lowest quartile. In men whose noise exposure is in 3rd quartile, odds ratio (OR) of severe teratozoospermia was 0.57 (95% CI: 0.33, 0.98). The OR for 4th quartile noise were toward null. In generalized additive model, the risk of oligozoospermia increases when the nighttime noise is 55 Leq dB or higher. Our study adds an evidence of potential impact of environmental noise on semen quality in men living in Seoul. Additional studies with more refined noise measurement will confirm the finding.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33037721

RESUMO

The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc-99m GRFLTGGTGRLLRIS-GHEG-ECG-K(-5-carboxy-X-rhodamine)-NH2 (GRFLT-ECG-ROX), and to verify its feasibility as both molecular imaging and intraoperative guidance agent. GRFLT-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of GRFLT-ECG-ROX with Tc-99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed using LNCaP and PC-3 tumor-bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc-99m, Tc-99m GRFLT-ECG-ROX complexes were prepared in high yield (>96%). The binding affinity value (Kd ) of Tc-99m GRFLT-ECG-ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m GRFLT-ECG-ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real-time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc-99m GRFLT-ECG-ROX could provide both preoperative molecular imaging and fluorescence imaging guidance for tumor removal.

7.
Inorg Chem ; 59(21): 15807-15812, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33048533

RESUMO

Preferential formation of cis- or trans-palladium(II) complexes controlled via the exocyclic binding sites embedded in dithiamacrocycles (L1 = -S(CH2)2S-; L2 = -S(CH2)2O(CH2)2S-) is reported. From the reaction with K2PdCl4, the shorter sulfur-to-sulfur separation in L1 preferentially leads to the formation of cis-[Pd(L1)Cl2] (1), while L2, incorporating a larger sulfur-to-sulfur separation, coordinates in a trans fashion to form a cyclic dimer, trans-[Pd2(L2)2Cl4] (2). The observed results illustrate the possibility for the controlled formation of cis/trans square-planar complexes through binding-site design. When palladium(II) acetate was substituted for K2PdCl4 in the above reaction, L1 gave no product, while L2 resulted in the formation of a unique tripalladium(II) complex, [Pd3(L2)(CH3C(═N)OC(═N)CH3)(CH3COO)4] (3), in which three PdII atoms are linked by acetimidic anhydride, CH3C(═N)OC(═N)CH3, derived from the acetonitrile solvent employed. In the 1H NMR spectrum for 3, specific methylene signals for methylene protons adjacent to S donors exhibit large complexation-induced splitting of the geminal proton signals into axial and equatorial proton peaks, thus indicating magnetically nonequivalent geminal protons that reflect the restricted conformation of the metallabicycle.

8.
Nanomaterials (Basel) ; 10(6)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32486096

RESUMO

Highly dispersive molybdenum disulfide nanoflakes (MoS2 NFs), without any phase transition during the exfoliation process, are desirable for full utilization of their semiconductor properties in practical applications. Here, we demonstrate an innovate approach for fabricating MoS2 NFs by using hydrazine-assisted ball milling via the synergetic effect of chemical intercalation and mechanical exfoliation. The NFs obtained have a lateral size of 600-800 nm, a thickness less than 3 nm, and high crystallinity in the 2H semiconducting phase. They form a stable dispersion in various solvents, which will be helpful for many applications, due to the oxygen functional group. To investigate production of a two-dimensional (2D) photodetector, 2D semiconducting MoS2, MoS2-p-Si vertical devices were fabricated, and their optical properties were characterized. The photodiode exhibited consistent responses with excellent photo-switching characteristics with wavelengths of 850, 530, and 400 nm.

9.
Foods ; 9(3)2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32213876

RESUMO

The present study aimed to understand the drivers of liking dried apple and pear chips with various textures among Chinese (n = 58), Korean (n = 58), and US (n = 56) consumers. The possibility of hedonic transfer from snack texture preferences to fruit-chip texture preferences was also investigated among Chinese and Koreans. Fourteen fruit-chip samples with four textural properties (crispy, puffy, soft, and jelly-like) were selected. Consumers rated their level of liking for each sample, and then they performed hedonic-based projective mapping with the same samples. In the hedonic texture transfer investigation, consumers rated their acceptance of nine snacks with various textures but possessing similar textures to those of dried fruit samples. The data were analyzed by ANOVA and multiple factor analysis. Most consumers disliked samples with a soft or jelly-like texture, while liked samples with a crispy texture. Cross-cultural differences were observed in the liking of puffy samples, with both Chinese and Koreans liking puffy samples as much as crispy ones for their melting characteristics in the mouth, while US consumers perceived the puffy samples as being Styrofoam-like and disliked them. Hedonic transfer was observed from snack texture preferences to fruit-chip. Individual texture preferences for snacks seem to significantly affect the texture preferences for fruit chips.

10.
Dalton Trans ; 49(5): 1365-1369, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31894796

RESUMO

A combination of O3S2-macrocycles incorporating different sulfur-to-sulfur separations (S-(CH2)n-S, L1: n = 2, L2: n = 3) and copper(ii) nitrate afforded new types of both monocopper(ii) and dicopper(ii) complexes, respectively. L1 gave a 1D coordination polymer [Cu2(L1)2(NO3)4]n (1) based on a convergent exo-coordination mode while L2 resulted in the formation of a divergent exo/exo-coordinated dicopper(ii) complex, [Cu2(L2ox)4(µ-Cl)](NO3)4 (2), whose shape resembles a four-bladed waterwheel in which in situ oxidized macrocycles (L2ox) act as the blades and a CuII-(µ-Cl)-CuII entity corresponds to the axle shaft. The chloro-bridging ligand is derived from the dichloromethane solvent and its arrangement is held together by C-HCl- H-bonds. Compound 2 shows a weak antiferromagnetic property via the CuII-(µ-Cl)-CuII entity.

11.
Med Sci Monit ; 25: 8438-8446, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705647

RESUMO

BACKGROUND Hypernatremia is associated with poor outcomes in critically ill patients, and an accurate assessment of water volume is important to determine appropriate fluid hydration. Bioelectrical impedance analysis (BIA) is a new, noninvasive, and relatively easy method for measuring hydration status. This study aimed to investigate whether bioelectrical impedance measurements of body water could reduce the frequency of blood sampling for fluid replacement in patients with hypernatremia. MATERIAL AND METHODS Fifty-one hospitalized patients were studied with hypernatremia, defined as a serum sodium ≥150 mmol/L determined by laboratory testing. Laboratory and BIA measurements were compared, and water deficiency was calculated with a conventional formula (sodium-corrected Watson formula) and measured by BIA. RESULTS The value of the absolute fluid overload (AFO) equivalent to the overhydration (OH) value, determined using BIA, did not accurately represent water deficit in patients with hypernatremia (r=0.137, P=0.347). Although the total body water (TBW) measured by BIA showed a significant correlation with that determined by the conventional formula (r=0.861, P<0.001), there was a proportional bias (r=0.617, P<0.001). The intracellular water (ICW) measured by BIA underestimated the TBW level calculated by the conventional formula by about 14.06±4.0 L in the Bland-Altman analysis. CONCLUSIONS It is not currently possible to replace blood testing with BIA for assessing volume status in hypernatremic patients. However, ICW value measured by BIA might represent plasma sodium level more accurately than extracellular water (ECW) or TBW value in patients with hypernatremia.


Assuntos
Hipernatremia/diagnóstico , Hipernatremia/metabolismo , Estado de Hidratação do Organismo/fisiologia , Adulto , Composição Corporal , Água Corporal/fisiologia , Desidratação/diagnóstico , Impedância Elétrica , Espaço Extracelular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Água
12.
Adv Mater ; 31(39): e1902902, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402565

RESUMO

Chemical interaction at a heterojunction interface induced by an appropriate chemical linker is of crucial importance for high efficiency, hysteresis-less, and stable perovskite solar cells (PSCs). Effective interface engineering in PSCs is reported via a multifunctional chemical linker of 4-imidazoleacetic acid hydrochloride (ImAcHCl) that can provide a chemical bridge between SnO2 and perovskite through an ester bond with SnO2 via esterification reaction and an electrostatic interaction with perovskite via imidazolium cation in ImAcHCl and iodide anion in perovskite. In addition, the chloride anion in ImAcHCl plays a role in the improvement of crystallinity of perovskite film crystallinity. The introduction of ImAcHCl onto SnO2 realigns the positions of the conduction and valence bands upwards, reduces nonradiative recombination, and improves carrier life time. As a consequence, average power conversion efficiency (PCE) is increased from 18.60% ± 0.50% to 20.22% ± 0.34% before and after surface modification, respectively, which mainly results from an enhanced voltage from 1.084 ± 0.012 V to 1.143 ± 0.009 V. The best PCE of 21% is achieved by 0.1 mg mL-1 ImAcHCl treatment, along with negligible hysteresis. Moreover, an unencapsulated device with ImAcHCl-modified SnO2 shows much better thermal and moisture stability than unmodified SnO2 .

13.
Nanoscale ; 11(30): 14455-14464, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334742

RESUMO

We report here resistive switching memory characteristics of imidazolium lead iodide depending on the molar ratio of PbI2 to imidazolium iodide (ImI), that is, PbI2 : ImI = 1 : 0, 1 : 0.5, 1 : 1, 1 : 2, 1 : 3 and 0 : 1. X-ray diffraction confirms that the stoichiometric composition results in a hexagonal structure of (Im)PbI3, showing a one-dimensional face-sharing [PbI3-] chain. Bipolar resistive switching characteristics are observed regardless of the mixing ratio, where the forming process is required prior to SET and RESET processes at around +0.2 V and -0.2 V, respectively. The ON/OFF ratio is increased from 106 to 109 as the ImI content is increased due to the increased HRS associated with the pronounced insulating characteristics by ImI, whereas, the stoichiometric (Im)PbI3 exhibits 5 times longer endurance (103) and an order of magnitude longer retention time (104 s) as compared to other compositions. Multilevel data storage capability is confirmed by changing the compliance current. The low resistance state (LRS) and the high resistance state (HRS) are associated with Ohmic conduction and Schottky conduction, respectively. Density functional theory (DFT) calculation reveals that the defect formation energy of iodine vacancy is estimated to be low indicating that (Im)PbI3 has a sufficient concentration of iodide vacancy for filament formation. Further energy barrier calculations show that iodide migration preferentially occurs along the 1-dimensional [234] crystallographic direction rather than the interlayer [130] direction. A good performance of the (Im)PbI3-based memristor is thus related to the low defect formation energy of iodide vacancy and the preferential growth of the filament along the 1-dimensional chain.

14.
Angew Chem Int Ed Engl ; 58(33): 11296-11300, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31209942

RESUMO

A one-pot reaction of the A1/A2-thiopyridyl pillar[5]arene L with silver(I) trifluoroacetate in the presence of the linear dinitrile guest C8, [CN(CH2 )n CN, n=8], afforded the first example of a two-dimensional (2D) poly-pseudo-rotaxane {[(µ4 -Ag)2 (C8@L)2 (µ-C8)](CF3 CO2 )2 }n . Surprisingly, in this structure the C8 guest not only threads into the pillar[5]arene unit but also crosslinks the 1D coordinative polymeric arrays. The formation of the 2D poly-pseudo-rotaxane is driven by an adaptive rearrangement of the components that minimizes the steric clashes not only between the threaded guests but also between the threaded and crosslinked guests where crosslinking occurs. A pathway for the formation of the 2D poly-pseudo-rotaxane is proposed.

15.
JMIR Mhealth Uhealth ; 7(6): e12645, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31228180

RESUMO

BACKGROUND: Lung cancer patients experience various symptoms during treatment. Although pulmonary rehabilitation is an effective way to improve these symptoms, a medical environment of limited availability makes it difficult to provide seamless and adequate rehabilitation for lung cancer patients. OBJECTIVE: This study aimed to investigate the effects of a personalized pulmonary rehabilitation program using real-time mobile patient health data for patients with non-small cell lung cancer. METHODS: We conducted a prospective clinical trial in 64 patients with non-small cell lung cancer aged between 20 and 80 years at a large tertiary hospital in Seoul, South Korea. A 12-week personalized pulmonary rehabilitation program, called efil breath, was administered to determine the effectiveness of the newly developed rehabilitation app. Participants were randomly allocated to the fixed exercise or fixed-interactive exercise group (which received the personalized program). We measured changes in 6-minute walk distance (6MWD) and dyspnea (modified Medical Research Council [mMRC] score) at 6 weeks; and quality of life and service satisfaction at 12 weeks. We used the paired t test to analyze the variables. RESULTS: Patients used the newly developed mobile health pulmonary rehabilitation app and a real-time patient monitoring website. In all participants, significant changes were observed in 6MWD at 12 weeks from a mean of 433.43m (SD 65.60) to 471.25m (SD 75.69; P=.001), and mMRC from a mean score of 0.94 (0.66) to 0.61 (SD 0.82; P=.02). The intervention significantly improved their quality of life (EuroQol-visual analog scale [EQ-VAS]) compared with baseline (mean score 76.05, SD 12.37 vs 82.09, SD 13.67, respectively; P=.002). CONCLUSIONS: A personalized mobile health-based pulmonary rehabilitation app for recording and monitoring real-time health data of patients with non-small cell lung cancer can supplement traditional health care center-based rehabilitation programs. This technology can encourage improvement of physical activity, dyspnea, and quality of life.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/reabilitação , Reabilitação/instrumentação , Adulto , Idoso , Exercício Físico/psicologia , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reabilitação/métodos , Autogestão/métodos , Autogestão/psicologia , Autogestão/estatística & dados numéricos , Seul , Telemedicina/instrumentação , Telemedicina/normas , Telemedicina/estatística & dados numéricos
16.
Ann Nucl Med ; 33(8): 606-616, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31134434

RESUMO

OBJECTIVE: Folate receptor (FR) is an ideal target for cancer imaging because it is frequently overexpressed in major types of human tumor, whereas its expression in normal organs is highly limited. Combining nuclear and fluorescence-imaging techniques provides a novel approach for cancer imaging and monitoring the surgery. The objective of this study was to report the synthesis and characteristics of a dual-modality imaging agent, Tc-99m Folate-Gly-His-Glu-Gly-Glu-Cys-Gly-Lys(-5-carboxy-X-rhodamine)-NH2 (Folate-ECG-ROX), and verify its feasibility as both molecular imaging agent and intra-operative guidance. METHODS: Folate-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of Folate-ECG-ROX with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed using KB and HT-1080 tumor-bearing murine models. Tumor tissue slides were prepared and analyzed with immunohistochemistry staining and confocal microscopy. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under the fluorescence-imaging system. RESULTS: After radiolabeling procedures with Tc-99m, Tc-99m Folate-ECG-ROX complexes were prepared in high yield (> 97%). The binding affinity value (Kd) of Tc-99m Folate-ECG-ROX for KB cells was estimated to be 6.9 ± 0.9 nM. In gamma camera imaging, tumor to normal muscle uptake ratio of Tc-99m Folate-ECG-ROX increased with time (3.4 ± 0.4, 4.4 ± 0.7, and 6.6 ± 0.8 at 1, 2, and 3 h, respectively). In biodistribution study, %IA/g for KB tumor was 2.50 ± 0.80 and 4.08 ± 1.16 at 1 and 3 h, respectively. Confocal microscopy with immunohistochemistry staining detected strong Tc-99m Folate-ECG-ROX fluorescence within KB tumor tissue which is correlating with the fluorescent activity of anti-FR antibody. Under real-time optical imaging, the removal of visible nodules was successfully performed. CONCLUSIONS: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m Folate-ECG-ROX in FR-positive tumors. Thus, Tc-99m Folate-ECG-ROX could provide both pre-operative molecular imaging and fluorescence image-guidance for tumor.


Assuntos
Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Imagem Óptica/métodos , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Cirurgia Assistida por Computador , Animais , Transporte Biológico , Transformação Celular Neoplásica , Estudos de Viabilidade , Feminino , Ácido Fólico/farmacocinética , Humanos , Marcação por Isótopo , Células KB , Camundongos , Compostos de Organotecnécio/química , Distribuição Tecidual
17.
Int J Pharm ; 565: 233-241, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31075439

RESUMO

We propose a polymeric nanovehicles (PNVs)-based enhanced transdermal delivery platform. A technical advance can be found in that delivery efficiency is significantly enhanced by effective adhesion of PNVs to the cell membrane, which is characterized noninvasively by using a confocal laser scanning microscopy (CLSM)-based skin visualization technique. To this end, the PNVs with a soft core phase were fabricated through co-assembly of two amphiphilic triblock copolymers, poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO). The softness of PNVs was tuned successfully, while maintaining the particle size at ∼110 nm, by incorporation of PEO-b-PPO-b-PEO into the PNVs to a volume fraction of 0.3. Through an ex vivo skin penetration test, we showed that transactivating transcriptional activator (TAT)-decorated soft PNVs could not only exert strong adhesion to skin but also increase cellular uptake, leading to a transdermal delivery efficiency that is twice that of a hard PNV control. Moreover, CLSM-based noninvasive visualization of a fluorescent drug probe in the skin showed that the adhesiveness and softness of the PNVs contributed directly to the enhancement of transdermal delivery.


Assuntos
Membrana Celular , Sistemas de Liberação de Medicamentos , Fragmentos de Peptídeos/administração & dosagem , Poliésteres/administração & dosagem , Polietilenoglicóis/administração & dosagem , Propilenoglicóis/administração & dosagem , Produtos do Gene tat do Vírus da Imunodeficiência Humana/administração & dosagem , Adesividade , Administração Cutânea , Animais , Linhagem Celular Tumoral , Humanos , Microscopia Confocal , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Propilenoglicóis/química , Pele/metabolismo , Absorção Cutânea , Suínos
18.
J Sci Food Agric ; 99(11): 5092-5101, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30982970

RESUMO

BACKGROUND: This study identified and compared the drivers of liking for fresh pears cross-culturally, using Korean and Chinese panels and consumers. The pear samples consisted of six types of fresh pear varying in flavor and texture qualities. The descriptive panels for the two countries independently derived descriptive terms for the pears. Acceptance testing was also conducted to examine the hedonic levels of fresh pears among Chinese and Korean consumers. Multivariate analysis of variance, using a general linear model (GLM), and multiple-factor analysis were applied to the descriptive data. The consumer test data were analyzed using a GLM, correspondence analysis, and internal preference mapping. RESULTS: The results showed that the overall perceptual configurations of pears developed by the Chinese and Korean panels were similar. The consumer liking for fresh pears and the drivers of liking were also cross-culturally similar. Consumers from both countries liked crisp and juicy Asian pears but they had different perceptions of and liking for the pear with a strong fruity note and soft texture. This observation was supported by the results of the descriptive analysis, which showed that the Chinese panel considered this pear sample to be fruity and have an harmonious flavor, whereas the Korean panel - which was less familiar with the sample - considered its flavor unharmonious. CONCLUSION: Previous cross-cultural studies have often found that food acceptance levels vary markedly with the degree of familiarity with target foodstuffs. However, unlike other food categories, the difference seems relatively small for fruits that are commonly available across cultures. © 2019 Society of Chemical Industry.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , Comportamento do Consumidor , Pyrus/química , Adulto , China , Comportamento do Consumidor/estatística & dados numéricos , Comparação Transcultural , Feminino , Preferências Alimentares/psicologia , Frutas/química , Frutas/classificação , Frutas/metabolismo , Humanos , Masculino , Pyrus/classificação , Pyrus/metabolismo , República da Coreia , Paladar , Adulto Jovem
19.
Tumori ; 105(3): 216-224, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30905312

RESUMO

BACKGROUND: This study aimed to estimate therapeutic effects of first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in real-world practice, by analyzing survival outcomes in an unselected, Korean female population with advanced lung cancer based on the National Health Insurance Service database. METHODS: We identified women with newly diagnosed advanced lung cancer from January 2004 to December 2013. For progression-free survival (PFS) and overall survival (OS) analyses, patients were defined into the following subgroups: group A, treated with first-generation EGFR-TKI ⩾6 months; group B, treated with EGFR-TKIs <6 months but at least >1 month; and group C, treated with cytotoxic chemotherapy as follows: monotherapy or combination therapy with gemcitabine or pemetrexed; or monotherapy with docetaxel, paclitaxel, or vinorelbine. RESULTS: Among 11,045 enrolled patients, 6170 (55.8%) were treated with first-generation EGFR-TKIs for at least 1 month. The median OS for patients treated with EGFR-TKIs was significantly longer than that of EGFR-TKI-naive patients (19.1 months [95% confidence interval (CI) 18.5-19.7] vs 9.5 months [95% CI 9.1-9.8], P<0.001). In subgroup analysis, group A had a significantly longer median OS compared with group B (30.3 months [95% CI 29.5-31.2] vs 12.3 months [95% CI 11.9-12.7], P<0.001). The median PFS of group A was significantly longer than that of group B (15.8 vs 3.7 months, P<0.001). CONCLUSIONS: Our analysis demonstrates that EGFR-TKIs confer significant PFS and OS benefits in the real-world practice for Korean female with advanced lung cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Idoso , Carcinoma Pulmonar de Células não Pequenas , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Intervalo Livre de Progressão
20.
EBioMedicine ; 40: 184-197, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30686754

RESUMO

BACKGROUND: Fast growing cancer cells require greater amounts of ATP than normal cells. Although glycolysis was suggested as a source of anabolic metabolism based on lactate production, the main source of ATP to support cancer cell metabolism remains unidentified. METHODS: We have proposed that the oxoglutarate carrier SLC25A11 is important for ATP production in cancer by NADH transportation from the cytosol to mitochondria as a malate. We have examined not only changes of ATP and NADH but also changes of metabolites after SLC25A11 knock down in cancer cells. FINDINGS: The mitochondrial electron transport chain was functionally active in cancer cells. The cytosolic to mitochondrial NADH ratio was higher in non-small cell lung cancer (NSCLC) and melanoma cells than in normal cells. This was consistent with higher levels of the oxoglutarate carrier SLC25A11. Blocking malate transport by knockdown of SLC25A11 significantly impaired ATP production and inhibited the growth of cancer cells, which was not observed in normal cells. In in vivo experiments, heterozygote of SLC25A11 knock out mice suppressed KRASLA2 lung tumor formation by cross breeding. INTERPRETATION: Cancer cells critically depended on the oxoglutarate carrier SLC25A11 for transporting NADH from cytosol to mitochondria as a malate form for the purpose of ATP production. Therefore blocking SLC25A11 may have an advantage in stopping cancer growth by reducing ATP production. FUND: The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to SYK (NRF-2017R1A2B2003428).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Transformação Celular Neoplásica/genética , Neoplasias Pulmonares/genética , Melanoma/genética , Proteínas de Membrana Transportadoras/deficiência , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Genes ras , Xenoenxertos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Melanoma/metabolismo , Melanoma/patologia , Potencial da Membrana Mitocondrial/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Biológicos , Mutação , Transporte Proteico
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