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1.
Yi Chuan ; 43(11): 1078-1087, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34815210

RESUMO

Cold stress is the limiting factor of rice growth and production, and it is important to clone cold stress tolerant genes and cultivate cold tolerance rice varieties. The MADS transcription factors play an important role in abiotic stress signaling in rice. This study showed that OsMADS25 was up-regulated by low temperature and abscisic acid (ABA), suggesting that OsMADS25 may be involved in ABA-dependent signaling. The OsMADS25 overexpression vector, pCambia1300-221-OsMADS25-Flag, was constructed and introduced into the rice variety Zhonghua 11 (ZH11) through Agrobacterium tumefacian-mediated genetic transformation. Two homozygous lines with high expression levels were selected for phenotypic identification. OsMADS25 overexpression lines show significantly improved cold stress tolerance and the sensitivity to ABA at the seedling stage of rice. Reactive oxygen species (ROS) was detected by diaminobenzidine (DAB) staining and nitroblue tetrazolium (NBT) staining. After treatment with cold stress, little ROS accumulation was observed in OsMADS25 overexpression lines compared to wild-type ZH11. In conclusion, OsMADS25 plays a role in scavenging reactive oxygen species (ROS) and could improve rice tolerance to cold stress involved in ABA-dependent pathway.


Assuntos
Oryza , Ácido Abscísico , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Mol Cancer Res ; 19(11): 1929-1945, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34446542

RESUMO

Resistance to cyclin D-CDK4/6 inhibitors (CDK4/6i) represents an unmet clinical need and is frequently caused by compensatory CDK2 activity. Here we describe a novel strategy to prevent CDK4i resistance by using a therapeutic liposomal:peptide formulation, NP-ALT, to inhibit the tyrosine phosphorylation of p27Kip1(CDKN1B), which in turn inhibits both CDK4/6 and CDK2. We find that NP-ALT blocks proliferation in HR+ breast cancer cells, as well as CDK4i-resistant cell types, including triple negative breast cancer (TNBC). The peptide ALT is not as stable in primary mammary epithelium, suggesting that NP-ALT has little effect in nontumor tissues. In HR+ breast cancer cells specifically, NP-ALT treatment induces ROS and RIPK1-dependent necroptosis. Estrogen signaling and ERα appear required. Significantly, NP-ALT induces necroptosis in MCF7 ESRY537S cells, which contain an ER gain of function mutation frequently detected in metastatic patients, which renders them resistant to endocrine therapy. Here we show that NP-ALT causes necroptosis and tumor regression in treatment naïve, palbociclib-resistant, and endocrine-resistant BC cells and xenograft models, demonstrating that p27 is a viable therapeutic target to combat drug resistance. IMPLICATIONS: This study reveals that blocking p27 tyrosine phosphorylation inhibits CDK4 and CDK2 activity and induces ROS-dependent necroptosis, suggesting a novel therapeutic option for endocrine and CDK4 inhibitor-resistant HR+ tumors.

3.
Biomater Sci ; 9(14): 5000-5010, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34105535

RESUMO

A zwitterionic polymer-drug conjugate (ZPDC) strategy is developed for the co-delivery of paclitaxel (PTX) and gemcitabine (GEM) chemotherapeutics, as well as a near-infrared fluorescence imaging agent cyanine5.5 (Cy5.5). The well-defined ZPDC is synthesized by tandem azide-alkyne and thiol-ene click functionalization of a biodegradable acetylenyl/allyl-functionalized polylactide and zwitterionic character is conferred by sulfobetaine. It has a number-average molecular weight of 53.6 kDa, comprising 6.5% PTX and 17.7% GEM by weight. Cy5.5 moieties are readily introduced to the ZPDC via conjugation. In aqueous solutions, the ZPDC exhibits a hydrodynamic diameter of 46 nm. In vitro MIA PaCa-2 human pancreatic cancer cells show strong ZPDC cellular uptake and cytotoxicity. In mice, the ZPDC exhibits long blood circulation, effective tumor accumulation, biocompatibility, therapeutic effect, and integrated imaging capacity. Overall, this work illustrates that ZPDCs are promising systems for chemotherapy delivery and bioimaging applications.


Assuntos
Paclitaxel , Preparações Farmacêuticas , Animais , Betaína/análogos & derivados , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Sistemas de Liberação de Medicamentos , Camundongos , Polímeros
4.
Light Sci Appl ; 10(1): 5, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402668

RESUMO

Nanophotonic resonators can confine light to deep-subwavelength volumes with highly enhanced near-field intensity and therefore are widely used for surface-enhanced infrared absorption spectroscopy in various molecular sensing applications. The enhanced signal is mainly contributed by molecules in photonic hot spots, which are regions of a nanophotonic structure with high-field intensity. Therefore, delivery of the majority of, if not all, analyte molecules to hot spots is crucial for fully utilizing the sensing capability of an optical sensor. However, for most optical sensors, simple and straightforward methods of introducing an aqueous analyte to the device, such as applying droplets or spin-coating, cannot achieve targeted delivery of analyte molecules to hot spots. Instead, analyte molecules are usually distributed across the entire device surface, so the majority of the molecules do not experience enhanced field intensity. Here, we present a nanophotonic sensor design with passive molecule trapping functionality. When an analyte solution droplet is introduced to the sensor surface and gradually evaporates, the device structure can effectively trap most precipitated analyte molecules in its hot spots, significantly enhancing the sensor spectral response and sensitivity performance. Specifically, our sensors produce a reflection change of a few percentage points in response to trace amounts of the amino-acid proline or glucose precipitate with a picogram-level mass, which is significantly less than the mass of a molecular monolayer covering the same measurement area. The demonstrated strategy for designing optical sensor structures may also be applied to sensing nano-particles such as exosomes, viruses, and quantum dots.

5.
Materials (Basel) ; 13(7)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32224890

RESUMO

Nanoparticles have emerged as versatile carriers for various therapeutics and can potentially treat a wide range of diseases in an accurate and disease-specific manner. Polymeric biomaterials have gained tremendous attention over the past decades, owing to their tunable structure and properties. Aliphatic polyesters have appealing attributes, including biodegradability, non-toxicity, and the ability to incorporate functional groups within the polymer backbone. Such distinctive properties have rendered them as a class of highly promising biomaterials for various biomedical applications. In this article, well-defined alkyne-functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) diblock copolymer was synthesized and studied for pH-responsive delivery of doxorubicin (DOX). The alkyne-functionalized PEG-b-PCL diblock copolymer was prepared by the synthesis of an alkyne-functionalized ε-caprolactone (CL), followed by ring-opening polymerization (ROP) using PEG as the macroinitiator. The alkyne functionalities of PEG-b-PCL were modified through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction to graft aldehyde (ALD) groups and obtain PEG-b-PCL-g-ALD. Subsequently, DOX was conjugated on PEG-b-PCL-g-ALD through the Schiff base reaction. The resulting PEG-b-PCL-g-DOX polymer-drug conjugate (PDC) self-assembled into a nano-sized micellar structure with facilitated DOX release in acidic pH due to the pH-responsive linkage. The nanostructures of PDC micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). In vitro studies of the PDC micelles, revealed their improved anticancer efficiency towards MCF-7 cells as compared to free DOX.

6.
Langmuir ; 35(5): 1440-1449, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30086625

RESUMO

Zwitterionic cross-linked biodegradable nanocapsules (NCs) were synthesized for cancer imaging. A polylactide (PLA)-based diblock copolymer with two blocks carrying acetylenyl and allyl groups respectively was synthesized by ring-opening polymerization (ROP). Azide-alkyne "click" reaction was conducted to conjugate sulfobetaine (SB) zwitterions and fluorescent dye Cy5.5 onto the acetylenyl-functionalized first block of the diblock copolymer. The resulting copolymer with a hydrophilic SB/Cy5.5-functionalized PLA block and a hydrophobic allyl-functionalized PLA block could stabilize miniemulsions because of its amphiphilic diblock structure. UV-induced thiol-ene "click" reaction between a dithiol cross-linker and the hydrophobic allyl-functionalized block of the copolymer at the peripheral region of nanoscopic oil nanodroplets in the miniemulsion generated cross-linked polymer NCs with zwitterionic outer shells. These NCs showed an average hydrodynamic diameter ( Dh) of 136 nm. They exhibited biodegradability, biocompatibility and high colloidal stability. In vitro study indicated that these NCs could be taken up by MIA PaCa-2 cancer cells. In vivo imaging study showed that, comparing to a small molecule dye, NCs had a longer circulation time, facilitating their accumulation at tumors for cancer imaging. Overall, this work demonstrates the applicability of zwitterionic biodegradable polymer-based materials in cancer diagnosis.


Assuntos
Nanocápsulas/química , Neoplasias/diagnóstico por imagem , Animais , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/toxicidade , Carbocianinas/síntese química , Carbocianinas/química , Carbocianinas/toxicidade , Bovinos , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Feminino , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/toxicidade , Humanos , Camundongos Nus , Nanocápsulas/toxicidade , Imagem Óptica/métodos , Poliésteres/síntese química , Poliésteres/química , Poliésteres/toxicidade
7.
Nanoscale Adv ; 1(7): 2761-2771, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32864564

RESUMO

A multifunctional biodegradable brush polymer-drug conjugate (BPDC) is developed for the co-delivery of hydrophobic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) chemotherapeutics, as well as a tumor imaging agent. A novel ternary copolymer of conventional, acetylenyl-functionalized and allyl-functionalized lactides is prepared to serve as the backbone precursor of BPDC. Acetylenyl groups of the copolymer are then reacted with poly(ethylene glycol) (PEG) side chains and cyanine5.5, a fluorescent probe, via azide-alkyne click reactions. Subsequently, the allyl groups of the yielded PEG-grafted brush polymer are used to covalently link PTX and GEM onto the backbone via thiol-ene click reactions. The resulting BPDC exhibits an average hydrodynamic diameter of 111 nm. Sustained and simultaneous release of PTX and GEM from the BPDC is observed in phosphate buffered saline, with the release of PTX showing sensitivity in mild acidic conditions. In vitro studies using MIA PaCa-2 human pancreatic cancer cells illustrate the cellular uptake and cytotoxicity of the BPDC. In vivo, the BPDC possesses long blood circulation, tumor accumulation, and enables optical tumor imaging. Further development and testing is warranted for multifunctional conjugated brush polymer systems that integrate combination chemotherapies and imaging.

8.
ACS Appl Mater Interfaces ; 10(51): 44231-44239, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30499652

RESUMO

Glutathione is overexpressed in tumor cells and regulates cancer growth, metastasis, and drug resistance. Therefore, detecting glutathione levels may greatly facilitate cancer diagnosis and treatment response monitoring. Photoacoustic (PA) imaging is a noninvasive modality for high-sensitivity, high-resolution, deep-tissue optical imaging. Switchable PA probes that offer signal on/off responses to tumor targets would further improve the detection sensitivity and signal-to-noise ratio of PA imaging. Here, we explore the use of MnO2 nanotubes as a switchable and biodegradable PA probe for dynamic imaging of glutathione in cancer. Glutathione reduces black MnO2 nanotubes into colorless Mn2+ ions, leading to decreased and signal off PA amplitude. In phantoms, we observed a linear response of reduced PA signals of MnO2 nanotubes to increased glutathione concentrations. Using melanoma as the disease model, we demonstrated that MnO2 nanotube-based PA imaging of glutathione successfully distinguished B16F10 melanoma cells from BEAS-2B normal cells and discriminated B16F10 tumors from healthy skin tissues. Our results showed that MnO2 nanotubes are a potent switchable and biodegradable PA probe for glutathione imaging in cancer diagnosis.


Assuntos
Glutationa/metabolismo , Compostos de Manganês , Melanoma , Nanotubos/química , Neoplasias Experimentais , Imagem Óptica/métodos , Óxidos , Técnicas Fotoacústicas/métodos , Neoplasias Cutâneas , Animais , Linhagem Celular Tumoral , Humanos , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Melanoma/diagnóstico por imagem , Melanoma/metabolismo , Camundongos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Óxidos/química , Óxidos/farmacologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/metabolismo
9.
Exp Aging Res ; 43(4): 379-390, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28718751

RESUMO

Background/Study Context: The face is the most distinctive physical feature of a person. Previous work has shown that one's own face (self-face) is advantageous in perception. Here the authors investigate how aging influences the configural and featural processing of self-face. METHODS: Older and young adults searched for their own faces and faces of strangers (Experiment 1) or acquaintances (Experiment 2) among distractor faces. The configural and featural processing of faces was assessed with face inversion in Experiment 1 and with changes in point of view in Experiment 2. RESULTS: Experiment 1 revealed a robust self-face advantage for upright faces in both young and older adults. A similar advantage was observed for inverted faces in young but not in older adults. Experiment 2 revealed a self-face advantage in older adults regardless of the point of view; in young adults, however, the self-face advantage only emerged for frontal view faces. CONCLUSION: The present study shows that older adults have a self-face advantage in configural but not in featural processing. The authors suggest that the impairment in featural processing in older adults is likely the result of age-related changes in perceptual experience.


Assuntos
Envelhecimento/psicologia , Reconhecimento Facial , Adulto , Idoso , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Psicológico , Adulto Jovem
10.
Genome Announc ; 4(1)2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26847883

RESUMO

Pseudomonas aeruginosa is a Gram-negative bacterium, which uses a variety of organic chemicals as carbon sources. Here, we report the genome sequence of the Cu1510 isolate from wastewater containing a high concentration of N,N-dimethyl formamide.

11.
Soc Neurosci ; 11(5): 507-14, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26513485

RESUMO

Numerous studies have shown there exist attention biases for self-related and negative stimuli. Few studies, however, have been carried out to compare the effects of such stimuli on the neural mechanisms of early attentional alertness and subsequent cognitive processing. The purpose of the present study was to examine the temporal primacy of both self-related stimuli and negative stimuli in the neurophysiologic level. In a modified oddball task, event-related potentials of the deviant stimuli (i.e., self-face, negative face and neutral face) were recorded. Results revealed that larger P2 amplitudes were elicited by self-related and negative stimuli than by neutral stimuli. Negative stimuli, however, elicited shorter P2 latencies than self-related and neutral stimuli. As for the N2 component, self-related and negative stimuli elicited smaller amplitudes and shorter latencies than neutral stimuli, but otherwise did not differ. Self-related stimuli also elicited larger P3 and late positive component (LPC) amplitudes than negative and neutral stimuli. The pattern of results suggests that the primacy of negative stimuli occurred at an early attention stage of processing, while the primacy of self-related stimuli occurred at the subsequent cognitive evaluation and memory stage.


Assuntos
Atenção/fisiologia , Encéfalo/fisiologia , Reconhecimento Facial/fisiologia , Autoimagem , Adulto , Análise de Variância , Eletroencefalografia , Potenciais Evocados , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Fatores de Tempo , Adulto Jovem
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