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1.
Plant J ; 118(3): 823-838, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38224529

RESUMEN

Acyl-acyl carrier protein (ACP) thioesterases (FAT) hydrolyze acyl-ACP complexes to release FA in plastids, which ultimately affects FA biosynthesis and profiles. Soybean GmFATA1 and GmFATA2 are homoeologous genes encoding oleoyl-ACP thioesterases whose role in seed oil accumulation and plant growth has not been defined. Using CRISPR/Cas9 gene editing mutation of Gmfata1 or 2 led to reduced leaf FA content and growth defect at the early seedling stage. In contrast, no homozygous double mutants were obtained. Combined this indicates that GmFATA1 and GmFATA2 display overlapping, but not complete functional redundancy. Combined transcriptomic and lipidomic analysis revealed a large number of genes involved in FA synthesis and FA chain elongation are expressed at reduced level in the Gmfata1 mutant, accompanied by a lower triacylglycerol abundance at the early seedling stage. Further analysis showed that the Gmfata1 or 2 mutants had increased composition of the beneficial FA, oleic acid. The growth defect of Gmfata1 could be at least partially attributed to reduced acetyl-CoA carboxylase activity, reduced abundance of five unsaturated monogalactosyldiacylglycerol lipids, and altered chloroplast morphology. On the other hand, overexpression of GmFATA in soybean led to significant increases in leaf FA content by 5.7%, vegetative growth, and seed yield by 26.9%, and seed FA content by 23.2%. Thus, overexpression of GmFATA is an effective strategy to enhance soybean oil content and yield.


Asunto(s)
Ácidos Grasos , Glycine max , Proteínas de Plantas , Tioléster Hidrolasas , Glycine max/genética , Glycine max/crecimiento & desarrollo , Glycine max/metabolismo , Glycine max/enzimología , Ácidos Grasos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Tioléster Hidrolasas/metabolismo , Tioléster Hidrolasas/genética , Semillas/crecimiento & desarrollo , Semillas/genética , Semillas/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Regulación de la Expresión Génica de las Plantas , Mutación , Sistemas CRISPR-Cas , Triglicéridos/metabolismo , Edición Génica
2.
Plant Cell Environ ; 46(4): 1264-1277, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35909262

RESUMEN

Plant vacuoles serve as the primary intracellular compartments for phosphorus (P) storage. The Oryza sativa genome contains three genes that encode SPX ( SYG1/ PHO81/ XPR1)-MFS ( Major Facility Superfamily) proteins (OsSPX-MFS1-3). The physiological roles of the three transporters under varying P conditions in laboratory and field are not known. To address this knowledge gap, we generated single, double and triple mutants for three OsSPX-MFS genes. All the mutants except Osspx-mfs2 display lower vacuolar Pi concentrations and OsSPX-MFSs overexpression plant display higher Pi accumulation, demonstrating that all OsSPX-MFSs are vacuolar Pi influx transporters. OsSPX-MFS3 plays the dominant role based on the phenotypes of single mutants in terms of growth, vacuolar and tissue Pi concentrations. OsSPX-MFS2 is the weakest and only functions as vacuole Pi sequestration in an Osspx-mfs1/3 background. The vacuolar Pi sequestration capacity was severely impaired in Osspx-mfs1/3 and Osspx-mfs1/2/3, which resulted in increased Pi allocation to aerial organs. High P in the panicle impaired panicle and fertility in Osspx-mfs1/3 and Osspx-mfs1/2/3. Osspx-mfs2 resulted in a more stable yield compared to the wild type under low P in field grown plants. The results suggest that alteration of vacuolar Pi sequestration may be a novel effective strategy to improve rice tolerance to low phosphorus in cropping systems.


Asunto(s)
Oryza , Fosfatos , Fosfatos/metabolismo , Oryza/genética , Homeostasis , Fósforo/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Transporte de Fosfato/genética
3.
Gastric Cancer ; 24(3): 624-639, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33515163

RESUMEN

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer mortality globally and a molecularly heterogeneous disease. Identifying the driver pathways in GC progression is crucial to improving the clinical outcome. Recent studies identified ASPM (abnormal spindle-like microcephaly-associated) and FOXM1 (Forkhead box protein M1) as novel Wnt and cancer stem cell (CSC) regulators; their pathogenetic roles and potential crosstalks in GC remain unclarified. METHODS: The expression patterns of ASPM isoforms and FOXM1 were profiled in normal gastric epithelial and GC tissues. The functional roles of ASPM and FOXM1 in Wnt activity, cancer stemness and GC progression, and the underlying signaling processes were investigated. RESULTS: Approximately one third of GC cells upregulate the expression of ASPM isoform I (ASPMiI) in their cytoplasm; the tumors with a high ASPMiI positive score (≥ 10%) are associated with a poor prognosis of the patients. Mechanistically, the molecular interplay among FOXM1, ASPMiI and DVL3 was found to converge on ß-catenin to control the Wnt activity and the stemness property of GC cells. This multi-mode Wnt-regulatory module serves to reinforce Wnt signals in CSCs by transcriptional regulation (FOXM1-ASPM), protein-protein interactions (ASPMiI-DVL3-ß-catenin), and nuclear translocation (FOXM1-ß-catenin). CONCLUSIONS: This study illuminates a novel Wnt- and stemness-regulatory mechanism in GC cells and identifies a novel subset of FOXM1highASPMiIhigh GC with potential to guide Wnt- and stemness-related diagnostics and therapies.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas/genética , Línea Celular Tumoral , China , Proteína Forkhead Box M1/metabolismo , Humanos , Proteínas del Tejido Nervioso/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Vía de Señalización Wnt
4.
Global Biogeochem Cycles ; 42(2)2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-32665747

RESUMEN

Quantifying human impacts on the N cycle and investigating natural ecosystem N cycling depend on the magnitude of inputs from natural biological nitrogen fixation (BNF). Here, we present two bottom-up approaches to quantify tree-based symbiotic BNF based on forest inventory data across the coterminous US plus SE Alaska. For all major N-fixing tree genera, we quantify BNF inputs using (1) ecosystem N accretion rates (kg N ha-1 yr-1) scaled with spatial data on tree abundance and (2) percent of N derived from fixation (%Ndfa) scaled with tree N demand (from tree growth rates and stoichiometry). We estimate that trees fix 0.30-0.88 Tg N yr-1 across the study area (1.4-3.4 kg N ha-1 yr-1). Tree-based N fixation displays distinct spatial variation that is dominated by two genera, Robinia (64% of tree-associated BNF) and Alnus (24%). The third most important genus, Prosopis, accounted for 5%. Compared to published estimates of other N fluxes, tree-associated BNF accounted for 0.59 Tg N yr-1, similar to asymbiotic (0.37 Tg N yr-1) and understory symbiotic BNF (0.48 Tg N yr-1), while N deposition contributed 1.68 Tg N yr-1 and rock weathering 0.37 Tg N yr-1. Overall, our results reveal previously uncharacterized spatial patterns in tree BNF that can inform large-scale N assessments and serve as a model for improving tree-based BNF estimates worldwide. This updated, lower BNF estimate indicates a greater ratio of anthropogenic to natural N inputs, suggesting an even greater human impact on the N cycle.

5.
J Pathol ; 249(4): 498-508, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31465125

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and treatment-resistant malignancy. The lack of pathway-informed biomarkers hampers the development of rational diagnostics or therapies. Recently, the protein abnormal spindle-like microcephaly-associated (ASPM) was identified as a novel Wnt and stemness regulator in PDAC, while the pathogenic roles of its protein isoforms remain unclarified. We developed novel isoform-specific antibodies and genetic knockdown (KD) of putative ASPM isoforms, whereby we uncovered that the levels of ASPM isoform 1 (iI) and ASPM-iII are variably upregulated in PDAC cells. ASPM isoforms show remarkably different subcellular locations; specifically, ASPM-iI is exclusively localized to the cortical cytoplasm of PDAC cells, while ASPM-iII is predominantly expressed in cell nuclei. Mechanistically, ASPM-iI co-localizes with disheveled-2 and active ß-catenin as well as the stemness marker aldehyde dehydrogenase-1 (ALDH-1), and its expression is indispensable for the Wnt activity, stemness, and the tumorigenicity of PDAC cells. By contrast, ASPM-iII selectively regulates the expression level of cyclin E and cell cycle progression in PDAC cells. The expression of ASPM-iI and ASPM-iII displays considerable intratumoral heterogeneity in PDAC tissues and only that of ASPM-iI was prognostically significant; it outperformed ALDH-1 staining and clinico-pathological variables in a multivariant analysis. Collectively, the distinct expression patterns and biological functions of ASPM isoforms may illuminate novel molecular mechanisms and prognosticators in PDAC and may pave the way for the development of therapies targeting this novel oncoprotein. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Asunto(s)
Carcinoma Ductal Pancreático/metabolismo , Ciclo Celular , Proliferación Celular , Células Madre Neoplásicas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neoplasias Pancreáticas/metabolismo , Vía de Señalización Wnt , Familia de Aldehído Deshidrogenasa 1/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/secundario , Línea Celular Tumoral , Ciclina E/metabolismo , Proteínas Dishevelled/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Células Madre Neoplásicas/patología , Proteínas del Tejido Nervioso/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Isoformas de Proteínas , beta Catenina/metabolismo
6.
Ecol Lett ; 20(7): 842-851, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28512925

RESUMEN

The rarity of nitrogen (N)-fixing trees in frequently N-limited higher-latitude (here, > 35°) forests is a central biogeochemical paradox. One hypothesis for their rarity is that evolutionary constraints limit N-fixing tree diversity, preventing N-fixing species from filling available niches in higher-latitude forests. Here, we test this hypothesis using data from the USA and Mexico. N-fixing trees comprise only a slightly smaller fraction of taxa at higher vs. lower latitudes (8% vs. 11% of genera), despite 11-fold lower abundance (1.2% vs. 12.7% of basal area). Furthermore, N-fixing trees are abundant but belong to few species on tropical islands, suggesting that low absolute diversity does not limit their abundance. Rhizobial taxa dominate N-fixing tree richness at lower latitudes, whereas actinorhizal species do at higher latitudes. Our results suggest that low diversity does not explain N-fixing trees' rarity in higher-latitude forests. Therefore, N limitation in higher-latitude forests likely results from ecological constraints on N fixation.


Asunto(s)
Nitrógeno , Árboles , Bosques , Fijación del Nitrógeno , América del Norte
7.
Ecology ; 98(12): 3127-3140, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28976548

RESUMEN

Symbiotic nitrogen (N) fixation provides a dominant source of new N to the terrestrial biosphere, yet in many cases the abundance of N-fixing trees appears paradoxical. N-fixing trees, which should be favored when N is limiting, are rare in higher latitude forests where N limitation is common, but are abundant in many lower latitude forests where N limitation is rare. Here, we develop a graphical and mathematical model to resolve the paradox. We use the model to demonstrate that N fixation is not necessarily cost effective under all degrees of N limitation, as intuition suggests. Rather, N fixation is only cost effective when N limitation is sufficiently severe. This general finding, specific versions of which have also emerged from other models, would explain sustained moderate N limitation because N-fixing trees would either turn N fixation off or be outcompeted under moderate N limitation. From this finding, four general hypothesis classes emerge to resolve the apparent paradox of N limitation and N-fixing tree abundance across latitude. The first hypothesis is that N limitation is less common at higher latitudes. This hypothesis contradicts prevailing evidence, so is unlikely, but the following three hypotheses all seem likely. The second hypothesis, which is new, is that even if N limitation is more common at higher latitudes, more severe N limitation might be more common at lower latitudes because of the capacity for higher N demand. Third, N fixation might be cost effective under milder N limitation at lower latitudes but only under more severe N limitation at higher latitudes. This third hypothesis class generalizes previous hypotheses and suggests new specific hypotheses. For example, greater trade-offs between N fixation and N use efficiency, soil N uptake, or plant turnover at higher compared to lower latitudes would make N fixation cost effective only under more severe N limitation at higher latitudes. Fourth, N-fixing trees might adjust N fixation more at lower than at higher latitudes. This framework provides new hypotheses to explain the latitudinal abundance distribution of N-fixing trees, and also provides a new way to visualize them. Therefore, it can help explain the seemingly paradoxical persistence of N limitation in many higher latitude forests.


Asunto(s)
Ecosistema , Fijación del Nitrógeno , Árboles/fisiología , Bosques , Nitrógeno , Suelo , Simbiosis
8.
Glob Chang Biol ; 23(11): 4777-4787, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28386964

RESUMEN

Symbiotic nitrogen (N)-fixing trees can drive N and carbon cycling and thus are critical components of future climate projections. Despite detailed understanding of how climate influences N-fixation enzyme activity and physiology, comparatively little is known about how climate influences N-fixing tree abundance. Here, we used forest inventory data from the USA and Mexico (>125,000 plots) along with climate data to address two questions: (1) How does the abundance distribution of N-fixing trees (rhizobial, actinorhizal, and both types together) vary with mean annual temperature (MAT) and precipitation (MAP)? (2) How will changing climate shift the abundance distribution of N-fixing trees? We found that rhizobial N-fixing trees were nearly absent below 15°C MAT, but above 15°C MAT, they increased in abundance as temperature rose. We found no evidence for a hump-shaped response to temperature throughout the range of our data. Rhizobial trees were more abundant in dry than in wet ecosystems. By contrast, actinorhizal trees peaked in abundance at 5-10°C MAT and were least abundant in areas with intermediate precipitation. Next, we used a climate-envelope approach to project how N-fixing tree relative abundance might change in the future. The climate-envelope projection showed that rhizobial N-fixing trees will likely become more abundant in many areas by 2080, particularly in the southern USA and western Mexico, due primarily to rising temperatures. Projections for actinorhizal N-fixing trees were more nuanced due to their nonmonotonic dependence on temperature and precipitation. Overall, the dominant trend is that warming will increase N-fixing tree abundance in much of the USA and Mexico, with large increases up to 40° North latitude. The quantitative link we provide between climate and N-fixing tree abundance can help improve the representation of symbiotic N fixation in Earth System Models.


Asunto(s)
Cambio Climático , Bosques , Fijación del Nitrógeno , Árboles/fisiología , México , Dinámica Poblacional , Lluvia , Simbiosis , Temperatura , Estados Unidos
10.
Opt Express ; 22(25): 31417-25, 2014 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-25607091

RESUMEN

A simple but robust ultra-broadband femtosecond optical gating method utilizing transient beam deflection effect is demonstrated with direct CCD imaging of the distorted single-color probe and the measurement of the chirp structure of a white light continuum generated from a CaF2 plate. The non-collinear configured beam deflection gating technique not only preserves all the advantages of the previous optical Kerr lens based gating methods, such as having no phase matching conditions, little dependence on probe intensity or special nonlinear media, and no requirements on the pump-probe polarization relationship, but it also extends the measurable probe bandwidth. Meanwhile, it is also proved that the current gating technique is easy-aligned, free from the influence of the pump-probe pulse-front mismatch and the probe beam profile, which is much convenient for the characterization of ultra-broadband light pulses in the applications of ultrafast spectroscopy.

11.
Int J Biol Macromol ; 253(Pt 5): 127231, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37804899

RESUMEN

To address the environmental and food contamination issues caused by plastics and microorganisms, antimicrobial films using natural polymers has attracted enormous attention. In this work, we proposed a green, convenient and fast approach to prepare antimicrobial films from chitosan (CS), bacterial cellulose (BC) and ε-polylysine (ε-PL). The effects of different concentrations of ε-PL (0 %, 0.25 %, 0.5 %, 0.75 %, 1 %, w/v) on the physicochemical properties and antibacterial activity of composite films (CS-DABC-x%PL) were systematically investigated. Furthermore, a comprehensive comparison with purely physically mixed CS-BC-x%PL films provides a deeper understanding of the subject matter. Characterization tests of the films were conducted using scanning electron microscope (SEM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The results suggested that the incorporation of 0.5 % ε-PL reduced the water solubility of the composite film by 19.82 %, along with improved the tensile strength and thermal stability by 37.31 % and 28.54 %. As ε-PL concentration increased to 1 %, the antibacterial performance of the films gradually enhanced. Additionally, the CS-DABC-0.5%PL film demonstrated effectiveness in delaying the deterioration of tilapia. These findings imply that this novel green packaging material holds significant potential in food preservation due to its promising antibacterial properties.


Asunto(s)
Antiinfecciosos , Quitosano , Quitosano/química , Celulosa/química , Polilisina/farmacología , Polilisina/química , Embalaje de Alimentos , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Conservación de Alimentos
12.
Int J Biol Macromol ; 226: 301-311, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36495997

RESUMEN

A natural biopolymer bilayer film based on chitosan and bacterial cellulose with a protective layer of pullulan was developed by a two-step solution casting method. Curcumin was incorporated as an active antioxidant and antibacterial agent into the inner layer. The films with different curcumin concentrations were systematically characterized. Fourier transform infrared spectroscopy and X-ray diffraction analyses showed high compatibility between curcumin and the polysaccharide matrix through intermolecular interactions, which was verified by enhanced mechanical and barrier properties. The curcumin incorporation improved the thermal stability by >35.4 %, along with lower visible and ultraviolet light transmittance (< 8.6 %) and water solubility (< 25.1 %). The film had both antibacterial and antioxidant properties, and the sustained release of curcumin was largest (> 58.8 %) in the fatty food simulant lasting for over 155 h. The results suggested that the film containing 0.2 % curcumin had ideal physical and functional properties, suggesting its potential as a novel packaging material for the preservation of high-fat food.


Asunto(s)
Quitosano , Curcumina , Quitosano/química , Celulosa/química , Curcumina/farmacología , Curcumina/química , Antioxidantes/farmacología , Antioxidantes/química , Preparaciones de Acción Retardada , Antibacterianos/farmacología , Antibacterianos/química , Embalaje de Alimentos/métodos
13.
Mol Plant ; 16(8): 1304-1320, 2023 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-37464739

RESUMEN

Vacuolar storage of inorganic phosphate (Pi) is essential for Pi homeostasis in plants. The SPX-MFS family proteins have been demonstrated to be vacuolar Pi transporters in many plant species. Transcriptional regulation of the predominant transporter among rice SPX-MFSs, OsSPX-MFS3, was only moderately suppressed by Pi starvation. Thus, post-transcriptional mechanisms were hypothesized to regulate the activity of OsSPX-MFS3. In this study, we found that the tonoplast localization of OsSPX-MFSs is inhibited under Pi-depleted conditions, resulting in their retention in the pre-vacuolar compartments (PVCs). A yeast two-hybrid screen identified that two SNARE proteins, OsSYP21 and OsSYP22, interact with the MFS domain of OsSPX-MFS3. Further genetic and cytological analyses indicate that OsSYP21 and OsSYP22 facilitate trafficking of OsSPX-MFS3 from PVCs to the tonoplast. Although a homozygous frameshift mutation in OsSYP22 appeared to be lethal, tonoplast localization of OsSPX-MFS3 was significantly inhibited in transgenic plants expressing a negative-dominant form of OsSYP22 (OsSYP22-ND), resulting in reduced vacuolar Pi concentrations in OsSYP22-ND plants. Under Pi-depleted conditions, the interaction between OsSYP22 and OsSPX-MFS3 was disrupted, and this process depended on the presence of the SPX domain. Deleting the SPX domains of OsSPX-MFSs resulted in their tonoplast localization under both Pi-depleted and Pi-replete conditions. Complementation of the osspx-mfs1/2/3 triple mutants with the MFS domain or the SPX domain of OsSPX-MFS3 confirmed that the MFS and SPX domains are responsive to Pi transport activity and Pi-dependent regulation, respectively. These data indicated that the SPX domains of OsSPX-MFSs sense cellular Pi (InsP) levels and, under Pi-depleted conditions, inhibit the interaction between OsSPX-MFSs and OsSYP21/22 and subsequent trafficking of OsSPX-MFSs from PVCs to the tonoplast.


Asunto(s)
Oryza , Fosfatos , Fosfatos/metabolismo , Oryza/genética , Oryza/metabolismo , Homeostasis , Plantas Modificadas Genéticamente/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo
14.
Cancer Res ; 83(6): 830-844, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36638332

RESUMEN

Small cell lung cancer (SCLC) is among the most aggressive and lethal human malignancies. Most patients with SCLC who initially respond to chemotherapy develop disease relapse. Therefore, there is a pressing need to identify novel driver mechanisms of SCLC progression to unlock treatment strategies to improve patient prognosis. SCLC cells comprise subsets of cells possessing progenitor or stem cell properties, while the underlying regulatory pathways remain elusive. Here, we identified the isoform 1 of the neurogenesis-associated protein ASPM (ASPM-I1) as a prominently upregulated stemness-associated gene during the self-renewal of SCLC cells. The expression of ASPM-I1 was found to be upregulated in SCLC cells and tissues, correlated with poor patient prognosis, and indispensable for SCLC stemness and tumorigenesis. A reporter array screening identified multiple developmental signaling pathways, including Hedgehog (Hh) and Wnt pathways, whose activity in SCLC cells depended upon ASPM-I1 expression. Mechanistically, ASPM-I1 stabilized the Hh transcriptional factor GLI1 at the protein level through a unique exon-18-encoded region by competing with the E3 ligases ß-TrCP and CUL3. In parallel, ASPM-I1 sustains the transcription of the Hh pathway transmembrane regulator SMO through the Wnt-DVL3-ß-catenin signaling axis. Functional studies verified that the ASPM-I1-regulated Hh and Wnt activities significantly contributed to SCLC aggressiveness in vivo. Consistently, the expression of ASPM-I1 positively correlated with GLI1 and stemness markers in SCLC tissues. This study illuminates an ASPM-I1-mediated regulatory module that drives tumor stemness and progression in SCLC, providing an exploitable diagnostic and therapeutic target. SIGNIFICANCE: ASPM promotes SCLC stemness and aggressiveness by stabilizing the expression of GLI1, DVL3, and SMO, representing a novel regulatory hub of Hh and Wnt signaling and targetable vulnerability.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Vía de Señalización Wnt , Carcinoma Pulmonar de Células Pequeñas/genética , Proteínas Hedgehog/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo , Línea Celular Tumoral , Recurrencia Local de Neoplasia/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Regulación Neoplásica de la Expresión Génica
15.
J Nat Prod ; 75(4): 630-5, 2012 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-22360613

RESUMEN

Breast cancer cells express ABCG2 transporters, which mediate multidrug resistance. Discovering a novel compound that can suppress ABCG2 expression and restore drug sensitivity could be the key to improving breast cancer therapeutics. In the current work, one new nor-neolignan, asperjinone (1), as well as 12 other known compounds, was isolated from Aspergillus terreus. The structure of the new isolate was determined by spectroscopic methods. Among these isolates, terrein (2) displayed strong cytotoxicity against breast cancer MCF-7 cells. Treatment with terrein (2) significantly suppressed growth of ABCG2-expressing breast cancer cells. This suppressive effect was achieved by inducing apoptosis via activating the caspase-7 pathway and inhibiting the Akt signaling pathway, which led to a decrease in ABCG2-expressing cells and a reduction in the side-population phenotype.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/efectos de los fármacos , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Aspergillus/química , Ciclopentanos/farmacología , Lignanos/aislamiento & purificación , Lignanos/farmacología , Proteínas de Neoplasias/efectos de los fármacos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Antineoplásicos/química , Neoplasias de la Mama/metabolismo , Caspasa 7/genética , Caspasa 7/metabolismo , Ciclopentanos/química , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Lignanos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Taiwán
16.
Carbohydr Polym ; 297: 120048, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36184184

RESUMEN

This study aimed to develop chitosan/bacterial cellulose-based films loaded with tea polyphenol-loaded chitosan coated nanoliposomes (CS-TP-lip) as an active agent for food preservation. The effects of the CS-TP-lip on the physicochemical properties of composite films were systematically evaluated. The CS-TP-lip exhibited spherical shapes with an average particle size of about 300 nm. Scanning electron microscopy and Fourier transform infrared spectroscopy analyses suggested high compatibility between the CS-TP-lip and film matrix through intermolecular interactions. Furthermore, due to the CS-TP-lip's presence, the elongation at break and thermal stability of the films could be enhanced to reach 75.14 ± 1.2 % and 395.33 °C, respectively, and the stability of tea polyphenol could be increased to prolong its functioning time. The films were successfully used as packaging materials for fish fillet preservation. Therefore, the developed nanocomposite films exhibit great promise as a new generation of biodegradable, sustainable, and bioactive film for food preservation.


Asunto(s)
Carpas , Quitosano , Animales , Celulosa , Quitosano/química , Embalaje de Alimentos/métodos , Polifenoles ,
17.
Nanoscale ; 14(30): 10918-10928, 2022 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-35852067

RESUMEN

In view of the weak aromatic characteristic resulting from the weak π-bonding ability (different from the analogous graphene), employing two-dimensional (2D) silicene and germanene monolayers could be one of the most promising ways to realize a new type of highly efficient and nonprecious catalyst for the hydrogen evolution reaction (HER). However, the HER activity of pristine silicene and germanene has to be improved, although both of them can exhibit a good change trend. Particularly, the hydrogen phenomenon can occur under moderate or high H* coverage on 2D silicene and germanene. To overcome these bottlenecks, in this study we identify the most effective strategy through doping P with a lone pair to significantly improve the HER catalytic activity under a high H* coverage, by screening a series of IIIA (i.e., B, Al, Ga, In and Tl) and VA (i.e., N, P, As, Sb and Bi) heteroatoms with different electronegativity under detailed DFT calculations. It is revealed that the doped P atoms and almost all the Si/Ge atoms can uniformly serve as highly active sites. Especially, in view of the existence of the lone pair, doping P effectively prevents hydrogenation (even under full H* coverage) by increasing the structural rigidity. Moreover, the P-doping concentration also plays a crucial role in obtaining high HER activity. The relevant mechanisms have been analyzed in detail. Clearly, all these fascinating findings are beneficial for realizing new HER electrocatalysts based on the excellent silicene or germanene nanomaterials, and even other Si/Ge-related materials in the near future.

18.
Nat Cancer ; 3(6): 734-752, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35618935

RESUMEN

Resistance to antitumor treatment contributes to patient mortality. Functional proteomic screening of organoids derived from chemotherapy-treated patients with breast cancer identified nuclear receptor corepressor 2 (NCOR2) histone deacetylase as an inhibitor of cytotoxic stress response and antitumor immunity. High NCOR2 in the tumors of patients with breast cancer predicted chemotherapy refractoriness, tumor recurrence and poor prognosis. Molecular studies revealed that NCOR2 inhibits antitumor treatment by regulating histone deacetylase 3 (HDAC3) to repress interferon regulatory factor 1 (IRF-1)-dependent gene expression and interferon (IFN) signaling. Reducing NCOR2 or impeding its epigenetic activity by modifying its interaction with HDAC3 enhanced chemotherapy responsiveness and restored antitumor immunity. An adeno-associated viral NCOR2-HDAC3 competitor potentiated chemotherapy and immune checkpoint therapy in culture and in vivo by permitting transcription of IRF-1-regulated proapoptosis and inflammatory genes to increase IFN-γ signaling. The findings illustrate the utility of patient-derived organoids for drug discovery and suggest that targeting stress and inflammatory-repressor complexes such as NCOR2-HDAC3 could overcome treatment resistance and improve the outcome of patients with cancer.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Detección Precoz del Cáncer , Femenino , Humanos , Recurrencia Local de Neoplasia , Co-Represor 2 de Receptor Nuclear/genética , Organoides/metabolismo , Proteómica
19.
Genes (Basel) ; 12(4)2021 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-33919786

RESUMEN

Iron (Fe) deficiency directly affects crop growth and development, ultimately resulting in reduced crop yield and quality. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to play critical regulatory roles in a multitude of pathways across numerous species. However, systematic screening of lncRNAs responding to Fe deficiency and their regulatory mechanism in plants has not been reported. In this work, 171 differently expressed lncRNAs (DE-lncRNAs) were identified based on analysis of strand-specific RNA-seq data from rice shoots and roots under Fe-deficient conditions. We also found several lncRNAs, which could generate miRNAs or act as endogenous target mimics to regulate expression of Fe-related genes. Analysis of interaction networks and gene ontology enrichment revealed that a number of DE-lncRNAs were associated with iron transport and photosynthesis, indicating a possible role of lncRNAs in regulation of Fe homeostasis. Moreover, we identified 76 potential lncRNA targets of OsbHLH156, a key regulator for transcriptional response to Fe deficiency. This study provides insight into the potential functions and regulatory mechanism of Fe-responsive lncRNAs and would be an initial and reference for any further studies regarding lncRNAs involved in Fe deficiency in plants.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Hierro/metabolismo , Oryza/crecimiento & desarrollo , ARN Largo no Codificante/genética , Regulación de la Expresión Génica de las Plantas , Ontología de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Oryza/genética , Oryza/metabolismo , Fotosíntesis , Raíces de Plantas/genética , ARN de Planta/genética , Análisis de Secuencia de ARN
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