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1.
Opt Express ; 30(23): 42406-42414, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36366695

RESUMEN

We demonstrated that a well-designed nanopatterned cover improves photovoltaic efficiency across a wide range of incident angles (θ). A nanopatterned cover was created using an integrated ray-wave optics simulation to maximize the light absorption of the surface-textured Si photovoltaic device. A hexagonally arranged nanocone array with a 300 nm pitch was formed into a polymer using nanoimprinting, and the nanostructured polymer was then attached to a glass cover with an index-matching adhesive. Angle-resolved current density-voltage measurements on Si photovoltaic devices showed that the nanopatterned glass cover yielded a 2-13% enhancement in power conversion efficiency at θ = 0-60°, which accounted for its broadband antireflective feature. We performed all-season-perspective simulations based on the results of the integrated ray-wave optics simulations and solar altitude database of South Korea, which validated the sustainability of the developed nanopatterned cover during significant seasonal fluctuations.

2.
Molecules ; 26(6)2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33804199

RESUMEN

Neuropathic pain is described as the "most terrible of all tortures that a nerve wound may inflict." The aim of the present study was to demonstrate the antinociceptive effect of Symplocos chinensis f. pilosa Ohwi water extract (SCW) and synthesized derivatives of the isolated compound. The antinociceptive effect was tested using the acetic acid-induced writhing and 5% formalin tests. Antinociceptive effects on neuropathic pain were evaluated using the von Frey test with chronic constriction injury (CCI) and surgical nerve injury (SNI) models and tail-flick test with a vincristine-induced pain model. An Ames test was also conducted. 5-hydroxymethylfurfural (5-HMF) was isolated and derivatives were synthesized with various acid groups. Among the plant water extracts, SCW showed significantly effective activity. Additionally, SCW presented antinociceptive effects in the neuropathic pain models. The SCW water fraction resulted in fewer writhes than the other fractions, and isolated 5-HMF was identified as an effective compound. Because 5-HMF revealed a positive response in the Ames test, derivatives were synthesized. Among the synthesized derivations, 5-succinoxymethylfurfural (5-SMF) showed the best effect in the neuropathic pain model. Our data suggest that SCW and the synthesized compound, 5-SMF, possess effective antinociceptive activity against neuropathic pain.


Asunto(s)
Ericales/química , Neuralgia/tratamiento farmacológico , Extractos Vegetales/farmacología , Analgésicos/farmacología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos ICR , Nervio Ciático/efectos de los fármacos
3.
J Cell Mol Med ; 22(9): 4117-4129, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29851245

RESUMEN

Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members generate phosphatidylinositol 4,5-bisphosphate (PIP2), a critical lipid regulator of diverse physiological processes. The PIP5K-dependent PIP2 generation can also act upstream of the oncogenic phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Many studies have demonstrated various mechanisms of spatiotemporal regulation of PIP5K catalytic activity. However, there are few studies on regulation of PIP5K protein stability. Here, we examined potential regulation of PIP5Kα, a PIP5K isoform, via ubiquitin-proteasome system, and its implication for breast cancer. Our results showed that the ubiquitin ligase NEDD4 (neural precursor cell expressed, developmentally down-regulated gene 4) mediated ubiquitination and proteasomal degradation of PIP5Kα, consequently reducing plasma membrane PIP2 level. NEDD4 interacted with the C-terminal region and ubiquitinated the N-terminal lysine 88 in PIP5Kα. In addition, PIP5Kα gene disruption inhibited epidermal growth factor (EGF)-induced Akt activation and caused significant proliferation defect in breast cancer cells. Notably, PIP5Kα K88R mutant that was resistant to NEDD4-mediated ubiquitination and degradation showed more potentiating effects on Akt activation by EGF and cell proliferation than wild-type PIP5Kα. Collectively, these results suggest that PIP5Kα is a novel degradative substrate of NEDD4 and that the PIP5Kα-dependent PIP2 pool contributing to breast cancer cell proliferation through PI3K/Akt activation is negatively controlled by NEDD4.


Asunto(s)
Membrana Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , Ubiquitina-Proteína Ligasas Nedd4/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Sistemas CRISPR-Cas , Línea Celular Tumoral , Membrana Celular/química , Membrana Celular/efectos de los fármacos , Proliferación Celular , Factor de Crecimiento Epidérmico/farmacología , Femenino , Edición Génica , Humanos , Mutación , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosforilación/efectos de los fármacos , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal , Ubiquitinación/efectos de los fármacos
4.
Anal Chem ; 90(21): 12937-12943, 2018 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-30303000

RESUMEN

The naphthoimidazolium borane 4 is shown to be a selective probe for HOCl over other reactive oxygen species. Unlike other boronate-reactive oxygen species (ROS) fluorogenic probes that are oxidized by HOCl through a nucleophilic borono-Dakin oxidation mechanism, probe 4 is distinguished by its electrophilic oxidation mechanism involving B-H bond cleavage. Two-photon microscopy experiments in living cells and tissues with the probe 4 demonstrate the monitoring of endogenous HOCl generation and changes in HOCl concentrations generated in the endoplasmic reticulum during oxidative stress situations.


Asunto(s)
Boranos/química , Retículo Endoplásmico/metabolismo , Colorantes Fluorescentes/química , Ácido Hipocloroso/análisis , Imidazoles/química , Animales , Boranos/síntesis química , Boranos/efectos de la radiación , Línea Celular Tumoral , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/efectos de la radiación , Humanos , Hidrólisis , Ácido Hipocloroso/metabolismo , Imidazoles/síntesis química , Imidazoles/efectos de la radiación , Masculino , Ratones , Microscopía/métodos , Oxidación-Reducción , Células RAW 264.7 , Ratas Sprague-Dawley , Rayos Ultravioleta
5.
Phys Chem Chem Phys ; 20(30): 19979-19986, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-30022200

RESUMEN

UV-UV hole burning and IR dip spectra of l-ß3-homotryptophan were measured by a laser desorption supersonic jet technique as a bottom-up approach to understand the secondary structures of ß-peptides. 14 conformers were found by UV-UV hole burning spectroscopy. The conformers were classified into three groups depending on their hydrogen bonding patterns observed in their conformer-specific IR spectra, and tentatively assigned by comparing with quantum chemical calculations. Group 1 had free OH stretch but no NH2 anti-symmetric stretch vibrational transition and was assigned to NH-π hydrogen bonded structures. Group 2, including the most abundant conformer, showed both free OH and NH2 anti-symmetric stretch vibrations, and belonged to NH-O hydrogen bonded conformations. Group 3 of conformers had hydrogen-bonded OH stretch IR transition and had OH-N hydrogen bonds. The internal hydrogen bond of group 3 is a C6 hydrogen bond due to the additional carbon atom at the ß position and shows a shorter bond length than that of a C5 hydrogen bond. While the OH-N C6 hydrogen bond is stronger than NH-O, the entropic effect prefers the more flexible NH-O hydrogen bonded structure. It is expected that the unnatural C6 hydrogen bond influences the conformations of ß-peptides and builds totally different secondary structures than those of α-peptides.


Asunto(s)
Triptófano/análogos & derivados , Triptófano/química , Entropía , Enlace de Hidrógeno , Modelos Moleculares , Conformación Molecular , Teoría Cuántica , Espectrofotometría Infrarroja/métodos
6.
Phys Chem Chem Phys ; 18(16): 11306-22, 2016 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-27054830

RESUMEN

The conformational preferences of a series of short, aromatic-capped, glutamine-containing peptides have been studied under jet-cooled conditions in the gas phase. This work seeks a bottom-up understanding of the role played by glutamine residues in directing peptide structures that lead to neurodegenerative diseases. Resonant ion-dip infrared (RIDIR) spectroscopy is used to record single-conformation infrared spectra in the NH stretch, amide I and amide II regions. Comparison of the experimental spectra with the predictions of calculations carried out at the DFT M05-2X/6-31+G(d) level of theory lead to firm assignments for the H-bonding architectures of a total of eight conformers of four molecules, including three in Z-Gln-OH, one in Z-Gln-NHMe, three in Ac-Gln-NHBn, and one in Ac-Ala-Gln-NHBn. The Gln side chain engages actively in forming H-bonds with nearest-neighbor amide groups, forming C8 H-bonds to the C-terminal side, C9 H-bonds to the N-terminal side, and an amide-stacked geometry, all with an extended (C5) peptide backbone about the Gln residue. The Gln side chain also stabilizes an inverse γ-turn in the peptide backbone by forming a pair of H-bonds that bridge the γ-turn and stabilize it. Finally, the entire conformer population of Ac-Ala-Gln-NHBn is funneled into a single structure that incorporates the peptide backbone in a type I ß-turn, stabilized by the Gln side chain forming a C7 H-bond to the central amide group in the ß-turn not otherwise involved in a hydrogen bond. This ß-turn backbone structure is nearly identical to that observed in a series of X-(AQ)-Y ß-turns in the protein data bank, demonstrating that the gas-phase structure is robust to perturbations imposed by the crystalline protein environment.


Asunto(s)
Glutamina/química , Péptidos/química , Conformación Proteica , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta
7.
Int J Mol Sci ; 16(4): 8102-9, 2015 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-25867480

RESUMEN

Emodin, an active constituent of oriental herbs, is widely used to treat allergy, inflammation, and other symptoms. This study provides the scientific basis for the anti-inflammasome effects of emodin on both in vitro and in vivo experimental models. Bone marrow-derived macrophages were used to study the effects of emodin on inflammasome activation by using inflammasome inducers such as ATP, nigericin, and silica crystals. The lipopolysaccharide (LPS)-induced endotoxin shock model was employed to study the effect of emodin on in vivo efficacy. Emodin treatment attenuated interleukin (IL)-1ß secretion via the inhibition of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation induced by ATP, nigericin, and silica crystals. Further, emodin ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin mouse models. This study is the first to reveal mechanism-based evidence, especially with respect to regulation of inflammasome activation, substantiating traditional claims of emodin in the treatment of inflammation-related disorders.


Asunto(s)
Antiinflamatorios/farmacología , Emodina/farmacología , Inflamasomas/metabolismo , Inflamación/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Animales , Proteínas Portadoras/metabolismo , Endotoxinas/farmacología , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Nigericina/metabolismo , Oxigenasas/metabolismo , Dióxido de Silicio/metabolismo
8.
Small Methods ; 8(1): e2301158, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37821419

RESUMEN

Alloying-type metallic tin is perceived as a potential anode material for K-ion batteries owing to its high theoretical capacity and reasonable working potential. However, pure Sn still face intractable issues of inferior K+ storage capability owing to the mechanical degradation of electrode against large volume changes and formation of intermediary insulating phases K4 Sn9 and KSn during alloying reaction. Herein, the TiC/C-carbon nanotubes (CNTs) is prepared as an effective buffer matrix and composited with Sn particles (Sn-TiC/C-CNTs) through the high-energy ball-milling method. Owing to the conductive and rigid properties, the TiC/C-CNTs matrix enhances the electrical conductivity as well as mechanical integrity of Sn in the composite material and thus ultimately contributes to performance supremacy in terms of electrochemical K+ storage properties. During potassiation process, the TiC/C-CNTs matrix not only dissipates the internal stress toward random radial orientations within the Sn particle but also provides electrical pathways for the intermediate insulating phases; this tends to reduce microcracking and prevent considerable electrode degradation.

9.
Phys Chem Chem Phys ; 15(3): 957-64, 2013 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-23207427

RESUMEN

Electronic and vibrational spectra of acetaminophen were measured by using UV-UV hole burning (HB) and IR dip spectroscopy. HB spectra show the coexistence of 4 different species, which include two new ones. Low-frequency transitions in the spectra are reproduced by a one-dimensional periodic potential with a free-rotor basis set for the methyl group. From the analysis, we concluded that acetaminophen has two conformers and each conformer gives two independent transitions starting from the most stable 0a(1) and the hot 1e internal rotational levels. It is also found that the HB spectrum of the trans-conformer in the previous report is that from the 1e excited level, while the HB spectrum of the cis-conformer is contaminated by the transitions of the trans-conformer. Potential curves of the methyl rotational motion are determined both in S(0) and S(1).


Asunto(s)
Acetaminofén/química , Gases/química , Espectrofotometría Infrarroja , Rayos Ultravioleta , Termodinámica
10.
J Chem Phys ; 139(12): 124311, 2013 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-24089771

RESUMEN

The deactivation process of adenine excited near the band origin of the lowest ππ* state ((1)L(b)) is investigated using picosecond (ps) time-resolved photoionization spectroscopy. The transients obtained with a ps pump pulse at the sharp vibronic bands, 36,105 cm(-1) (D) and 36,248 cm(-1) (E), in the resonant two-photon ionization spectrum exhibit a bi-exponential decay with two distinct time constants of τ1 ~ 2 ps and τ2 > 100 ps, whereas the transients with the pump at other wavenumbers in this energy region show a single exponential decay with τ = 1-2 ps. We suggest that the τ1 represents the lifetimes of the (1)nπ∗ energy levels near the D and E peaks, which are excited together by the ps pump pulse having a broad spectral bandwidth, and the τ2 shows the lifetimes of D and E peaks. The long lifetime of D level is attributed to a small barrier for internal conversion from the minimum of the (1)L(b) state to the (1)nπ* state. On the other hand, the long lifetime of E level is ascribed to the nuclear configuration of adenine at this level, which is unfavorable to reach the seam of the conical intersection leading to nearly barrierless deactivation to the electronic ground state. This study shows that the ps time-resolved spectroscopy provides a powerful tool to study mode- and energy-specific deactivation processes occurring in a multi-dimensional potential energy surface.


Asunto(s)
Adenina/química , Espectrometría de Masas , Estructura Molecular , Procesos Fotoquímicos , Fotones , Factores de Tiempo
11.
Adv Mater ; 35(32): e2209673, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37043776

RESUMEN

In the last decade, soft acoustic/vibration sensors have gained tremendous research interest due to their unique ability to detect broadband acoustic/vibration stimuli, potentializing futuristic applications including voice biometrics, voice-controlled human-machine-interfaces, electronic skin, and skin-mountable healthcare devices. Importantly, to benefit most from these sensors, it is inevitable to use machine learning (ML) to process their output signals; with ML, a more accurate and efficient interpretation of original data is possible. This paper is dedicated to offering an overview of recent advances empowering the development of soft acoustic/vibration sensors and their signal processing using ML. First, the key performance parameters of the sensors are discussed. Second, popular transduction mechanisms for the sensors are addressed, followed by an in-depth overview of each type, covering materials used, structural designs, and sensing performances. Third, potential applications of the sensors are elaborated and fourth, a thorough discussion on ML is conducted, exploring different types of ML, specific ML algorithms suitable for processing acoustic/vibration signals, and current trends in ML-assisted applications. Finally, the challenges and potential opportunities in soft acoustic/vibration sensor and ML research are revealed to offer new insights into future prospects in these fields.

12.
J Cosmet Dermatol ; 21(7): 3117-3126, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34841665

RESUMEN

INTRODUCTION: This study investigated the role of natural polymers as moisturizers with low toxicity and biodegradability in the cosmetic and pharmaceutical industries. We isolated a polysaccharide extract from Dendrobium candidum (D. candidum) and determined its efficacy in skin hydration when used as an active cosmetic ingredient. METHODS: The molecular weight distribution of D. candidum polysaccharides was analyzed via gel permeation chromatography (GPC). We performed real-time reverse transcription PCR (RT-PCR) and western blotting assays to investigate the physiological mechanism of the polysaccharides extracted from D. candidum (PDC). Based on in vitro data, the efficacy of PDC in improving skin condition was tested on the face of 21 volunteers. RESULTS: The expression of filaggrin (FLG), caspase-14, and bleomycin hydrolase, which are the major components contributing to skin hydration, was significantly increased in the PDC-treated group. Further, the PDC upregulated the mRNA expression of occludin and claudin-1, which play a key role in epidermal barrier function. In addition, a topical application of PDC markedly increased skin hydration and improved trans-epidermal water loss (TEWL) and skin elasticity after 2 weeks. CONCLUSIONS: It is the first study reporting the efficacy of PDC-mediated FLG mechanism associated with positive skin hydration. PDC can be used as an active ingredient in moisturizers. Long-term application of PDC-based moisturizers may result in significant improvement in elasticity and barrier function.


Asunto(s)
Dendrobium , Dendrobium/química , Epidermis/metabolismo , Humanos , Polisacáridos/metabolismo , Polisacáridos/farmacología , Piel
13.
Food Sci Nutr ; 10(7): 2381-2389, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35844922

RESUMEN

Caesalpinia eriostachys Benth. (CE) is native to the Mexico and multiple effects have been observed from several plants belonging to the same family. CE was subjected to extraction with 95% ethanol, and the components were isolated through column chromatography. The structure of the compound was elucidated based on nuclear magnetic resonance (NMR) spectral data, electron ionization-mass (EI-MS) spectroscopy, and liquid chromatography-mass (LC-MS) spectroscopy. In vivo antinociceptive studies were conducted using writhing, 5% formalin, tail-flick, hot-plate, and von Frey filament tests. The ethanolic extract showed a significant effect in the acetic acid-induced pain model and nociceptive behavior in the formalin model (second phase). In hot-plate test and tail-flick test, the results showed no difference compared to the control group. The results suggest that the ethanolic extract may act peripherally to reduce pain. In the streptozotocin (STZ)-induced pain model, the ethanolic extract showed significant effect in the von Frey test model. The n-Hex (Hexane) and MC (Methylene chloride) fractions and isolated compounds, ellagic acid and agathisflavone, showed increased effect. Based on these results, we confirmed that the CE ethanolic extract and their compounds, ellagic acid and agathisflavone, have antinociceptive effect on diabetes mellitus-induced pain. Furthermore, the results of this study might be valuable for identifying compounds with antinociceptive activity from natural products.

14.
Chemphyschem ; 12(10): 1935-9, 2011 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-21710523

RESUMEN

We investigated the decay dynamics of the DNA base pairs adenine-adenine (A(2)), adenine-thymine (AT), and thymine-thymine (T(2)) produced in a supersonic jet by femtosecond (fs) time-resolved photoionization spectroscopy. The base pair was excited by a fs pump pulse at 267 nm and the population change of its excited state was monitored by non-resonant three-photon ionization using a fs probe pulse at 800 nm after a certain time delay. All of the transients recorded in the mass channel of the parent ion exhibited a tri-exponential decay, with time constants ranging from 100 fs to longer than 100 ps. Most of these time constants coincide well with the previous values deduced indirectly from the transients of protonated adenine (AH(+)) and thymine (TH(+)), which were assumed to be produced by fragmentation of the base-pair ions. Notably, for the transient of T(2), we observed a new decay component with a time constant of 2.3 ps, which was absent in the transient of TH(+). We suggest that the new decay component arises from the decay of stacked T(2) dimers that are mostly ionized to T(2)(+), whereas the decay signal recorded in the mass channel of TH(+) is merely from the relaxation of hydrogen-bonded T(2) dimers. From the amplitude of the new decay component, the population of the stacked T(2) dimers relative to the hydrogen-bonded dimers was estimated to be ∼2 % in the supersonic jet, which is about fifteen times higher than the theoretical value.


Asunto(s)
Adenina/química , Timina/química , Emparejamiento Base , Dimerización , Enlace de Hidrógeno , Factores de Tiempo
15.
Phys Chem Chem Phys ; 13(15): 7037-42, 2011 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-21399792

RESUMEN

3-Aminophenol (3AP) has two conformers, cis and trans, depending on the orientation of the OH group relative to the NH(2) group. While both conformers are found in the jet-cooled spectra of 3AP, only the trans isomer was found in the REMPI spectrum of the 3AP(NH(3))(1) cluster. It was suggested that the cis conformer of the cluster isomerizes to the more stable trans conformer in the ground state during supersonic expansion. Solvent-assisted conformational isomerization (SACI) is believed to drive the population into the more stable trans isomer. SACI also occurs for the 3AP monomer, reducing 50% of the cis/trans ratio when the ammonia concentration in the expansion is higher than 0.1%. Depending on the expansion condition, the cis conformer can be completely depleted. When other solvents were introduced in the expansion, SACI occurred with only certain solvents whose binding energy is higher than the isomerization barrier. SACI can be used as a means to prepare the most stable conformer of gas phase biomolecules.


Asunto(s)
Aminofenoles/química , Conformación Molecular , Solventes/química , Análisis Espectral , Isomerismo , Modelos Moleculares
16.
J Chem Phys ; 134(7): 074307, 2011 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-21341844

RESUMEN

Vibrational and electronic spectra of protonated naphthalene (NaphH(+)) microsolvated by one and two water molecules were obtained by photofragmentation spectroscopy. The IR spectrum of the monohydrated species is consistent with a structure with the proton located on the aromatic molecule, NaphH(+)-H(2)O. Similar to isolated NaphH(+), the first electronic transition of NaphH(+)-H(2)O (S(1)) occurs in the visible range near 500 nm. The doubly hydrated species lacks any absorption in the visible range (420-600 nm) but absorbs in the UV range, similar to neutral Naph. This observation is consistent with a structure, in which the proton is located on the water moiety, Naph-(H(2)O)(2)H(+). Ab initio calculations for [Naph-(H(2)O)(n)]H(+) confirm that the excess proton transfers from Naph to the solvent cluster upon attachment of the second water molecule.


Asunto(s)
Electrones , Naftalenos/química , Protones , Agua/química , Modelos Moleculares , Conformación Molecular , Solventes/química , Espectrofotometría Infrarroja
17.
Mol Cell Proteomics ; 8(6): 1278-94, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19329653

RESUMEN

Tamoxifen resistance is a major cause of death in patients with recurrent breast cancer. Current clinical factors can correctly predict therapy response in only half of the treated patients. Identification of proteins that are associated with tamoxifen resistance is a first step toward better response prediction and tailored treatment of patients. In the present study we intended to identify putative protein biomarkers indicative of tamoxifen therapy resistance in breast cancer using nano-LC coupled with FTICR MS. Comparative proteome analysis was performed on approximately 5,500 pooled tumor cells (corresponding to approximately 550 ng of protein lysate/analysis) obtained through laser capture microdissection (LCM) from two independently processed data sets (n = 24 and n = 27) containing both tamoxifen therapy-sensitive and therapy-resistant tumors. Peptides and proteins were identified by matching mass and elution time of newly acquired LC-MS features to information in previously generated accurate mass and time tag reference databases. A total of 17,263 unique peptides were identified that corresponded to 2,556 non-redundant proteins identified with > or = 2 peptides. 1,713 overlapping proteins between the two data sets were used for further analysis. Comparative proteome analysis revealed 100 putatively differentially abundant proteins between tamoxifen-sensitive and tamoxifen-resistant tumors. The presence and relative abundance for 47 differentially abundant proteins were verified by targeted nano-LC-MS/MS in a selection of unpooled, non-microdissected discovery set tumor tissue extracts. ENPP1, EIF3E, and GNB4 were significantly associated with progression-free survival upon tamoxifen treatment for recurrent disease. Differential abundance of our top discriminating protein, extracellular matrix metalloproteinase inducer, was validated by tissue microarray in an independent patient cohort (n = 156). Extracellular matrix metalloproteinase inducer levels were higher in therapy-resistant tumors and significantly associated with an earlier tumor progression following first line tamoxifen treatment (hazard ratio, 1.87; 95% confidence interval, 1.25-2.80; p = 0.002). In summary, comparative proteomics performed on laser capture microdissection-derived breast tumor cells using nano-LC-FTICR MS technology revealed a set of putative biomarkers associated with tamoxifen therapy resistance in recurrent breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos , Proteínas de Neoplasias/metabolismo , Tamoxifeno/uso terapéutico , Secuencia de Aminoácidos , Neoplasias de la Mama/metabolismo , Cromatografía Liquida , Femenino , Humanos , Inmunohistoquímica , Datos de Secuencia Molecular , Proteínas de Neoplasias/química , Mapeo Peptídico , Espectrometría de Masas en Tándem , Tripsina/química
18.
ACS Appl Bio Mater ; 4(3): 2135-2141, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35014342

RESUMEN

Stomach cancer is a global health issue because of its incidence and mortality rates worldwide. We developed a near-infrared (NIR) emissive ratiometric two-photon (TP) probe (HCC1) for the quantitative analysis of pH in live cells and human stomach tissues. The probe design is based on a restrained hemicyanine core that controls the intramolecular charge transfer from 2-naphthol, with a suitable pKa value (7.50) under physiological conditions. The probe exhibited improved quantum yield, stability, and TP activity under physiological conditions. In addition, intracellular pH titration (pH 4.0 to 10.0) of HCC1 revealed an ideal intracellular pKa of approximately 7.2, negligible cytotoxicity, and TP excited fluorescence in situ, thereby allowing direct imaging of the cellular pH in live cells and tissues. Ratiometric two-photon microscope imaging with HCC1 of human stomach tissue revealed a clear intratissue pH variation among normal, adenoma, and cancer tissues. Our results demonstrate that HCC1 is useful as an NIR imaging probe for in situ pH-related studies and in cancer research.


Asunto(s)
Materiales Biocompatibles/química , Colorantes Fluorescentes/química , Fotones , Neoplasias Gástricas/diagnóstico por imagen , Línea Celular Tumoral , Humanos , Concentración de Iones de Hidrógeno , Ensayo de Materiales , Estructura Molecular , Tamaño de la Partícula , Neoplasias Gástricas/patología
19.
Chem Commun (Camb) ; 57(71): 8929-8932, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34397047

RESUMEN

A cyclocyanine (CC)-based organic small molecule two-photon (TP) fluorescent probe (CCNa1) was developed for mitochondrial sodium ion sensing. CCNa1 exhibits a low solvatochromic shift and strong TP fluorescence enhancement at 575 nm upon binding to Na+ and is insensitive to other metal ions and to pH. CCNa1 demonstrated fast cell loading ability, biocompatibility, and sensitive response to mitochondrial Na+ influx in live cells and mouse brain tissue.


Asunto(s)
Colorantes Fluorescentes/química , Mitocondrias/química , Sodio/análisis , Animales , Éteres Corona/química , Éteres Corona/efectos de la radiación , Éteres Corona/toxicidad , Colorantes Fluorescentes/efectos de la radiación , Colorantes Fluorescentes/toxicidad , Células HeLa , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/efectos de la radiación , Compuestos Heterocíclicos de 4 o más Anillos/toxicidad , Hipocampo/metabolismo , Humanos , Ratones , Fotones , Sodio/metabolismo
20.
Foods ; 10(5)2021 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-34068163

RESUMEN

Valeriana rigida Ruiz & Pav. (V. rigida) has long been used as a herbal medicine in Peru; however, its phytochemicals and pharmacology need to be scientifically explored. In this study, we combined the offline 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH)-/ultrafiltration-high-performance liquid chromatography (HPLC) and high-speed counter-current chromatography (HSCCC)/pH-zone-refining counter-current chromatography (pH-zone-refining CCC) to screen and separate the antioxidants and aldose reductase (AR) inhibitors from the 70% MeOH extract of V. rigida, which exhibited remarkable antioxidant and AR inhibitory activities. Seven compounds were initially screened as target compounds exhibiting dual antioxidant and AR inhibitory activities using DPPH-/ultrafiltration-HPLC, which guided the subsequent pH-zone-refining CCC and HSCCC separations of these target compounds, namely 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-O-di-caffeoylquinic acid, 3,5-O-di-caffeoylquinic acid, 4,5-O-di-caffeoylquinic acid, and 3,4,5-O-tri-caffeoylquinic acid. These compounds are identified for the first time in V. rigida and exhibited remarkable antioxidant and AR inhibitory activities. The results demonstrate that the method established in this study can be used to efficiently screen and separate the antioxidants and AR inhibitors from natural products and, particularly, the root extract of V. rigida is a new source of caffeoylquinic acids with antioxidant and AR inhibitory activities, and it can be used as a potential functional food ingredient for diabetes.

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