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1.
Mol Ther ; 32(3): 749-765, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38310356

RESUMEN

Approximately 80%-90% of hepatocellular carcinomas (HCC) occur in a premalignant environment of fibrosis and abnormal extracellular matrix (ECM), highlighting an essential role of ECM in the tumorigenesis and progress of HCC. However, the determinants of ECM in HCC are poorly defined. Here, we show that nuclear receptor RORγ is highly expressed and amplified in HCC tumors. RORγ functions as an essential activator of the matrisome program via directly driving the expression of major ECM genes in HCC cells. Elevated RORγ increases fibronectin-1 deposition, cell-matrix adhesion, and collagen production, creating a favorable microenvironment to boost liver cancer metastasis. Moreover, RORγ antagonists effectively inhibit tumor growth and metastasis in multiple HCC xenografts and immune-intact models, and they effectively sensitize HCC tumors to sorafenib therapy in mice. Notably, elevated RORγ expression is associated with ECM remodeling and metastasis in patients with HCC. Taken together, we identify RORγ as a key player of ECM remodeling in HCC and as an attractive therapeutic target for advanced HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Línea Celular Tumoral , Sorafenib , Colágeno/metabolismo , Microambiente Tumoral
2.
Anal Chem ; 96(16): 6390-6397, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38608159

RESUMEN

Although gastric cancer (GC) is one of the most frequent malignant tumors in the digestive tract with high morbidity and mortality, it remains a diagnostic dilemma due to its reliance on invasive biopsy or insensitive assays. Herein, we report a fluorescent gastric cancer reporter (FGCR) with activatable near-infrared fluorescence (NIRF) signals and high renal-clearance efficiency for the detection of orthotopic GC in a murine model via real-time imaging and remote urinalysis. In the presence of gastric-tumor-associated ß-galactosidase (ß-Gal), FGCR can be fluorescently activated for in vivo NIRF imaging. Relying on its high renal-clearance efficiency (∼95% ID), it can be rapidly excreted through kidneys to urine for the ultrasensitive detection of tumors with a diameter down to ∼2.1 mm and for assessing the prognosis of oxaliplatin-based chemotherapy. This study not only provides a new approach for noninvasive auxiliary diagnosis and prognosis of GC but also provides guidelines for the development of fluorescence probes for cancer diagnosis.


Asunto(s)
Colorantes Fluorescentes , Imagen Óptica , Neoplasias Gástricas , beta-Galactosidasa , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/orina , Neoplasias Gástricas/patología , Animales , beta-Galactosidasa/metabolismo , Colorantes Fluorescentes/química , Humanos , Ratones , Línea Celular Tumoral , Ratones Desnudos
3.
PLoS Pathog ; 18(3): e1010366, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35235615

RESUMEN

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.


Asunto(s)
Quinurenina 3-Monooxigenasa , Virosis , Animales , Calcio/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Factor 3 Regulador del Interferón/metabolismo , Quinurenina/metabolismo , Quinurenina 3-Monooxigenasa/metabolismo , Ratones , Ácido Quinolínico/metabolismo , Ácido Quinolínico/farmacología , Virosis/tratamiento farmacológico
4.
Chemistry ; 30(9): e202302889, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-37974486

RESUMEN

Herein, we describe how computational mechanistic understanding has led directly to the discovery of new 2H-phosphindole for C-CAr bond activation and dearomatization reaction. We uncover an unexpected intramolecular C-H bond activation with a 2H-phosphindole derivative. This new intriguing experimental observation and further theoretical studies led to an extension of the reaction mechanism with 2H-phosphindole. Through DFT calculations, we confirm that within a five-membered ring, the polarizable PC3 unit orchestrates the formation of an electrophilic phosphorus atom (P+ ) and a nucleophilic carbon atom (C- ). This kinetically accessible ambiphilic phosphorus/carbon couple is spatially separated by geometric constraints, and their reactivity is modulated through structural resonance.

5.
Environ Sci Technol ; 58(13): 5856-5865, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38516968

RESUMEN

Measuring the quantum yield and reactivity of triplet-state dissolved organic matter (3DOM*) is essential for assessing the impact of DOM on aquatic photochemical processes. However, current 3DOM* quantification methods require multiple fitting steps and rely on steady-state approximations under stringent application criteria, which may introduce certain inaccuracies in the estimation of DOM photoreactivity parameters. Here, we developed a global kinetic model to simulate the reaction kinetics of the hv/DOM system using four DOM types and 2,4,6-trimethylphenol as the probe for 3DOM*. Analyses of residuals and the root-mean-square error validated the exceptional precision of the new model compared to conventional methods. 3DOM* in the global kinetic model consistently displayed a lower quantum yield and higher reactivity than those in local regression models, indicating that the generation and reactivity of 3DOM* have often been overestimated and underestimated, respectively. The global kinetic model derives parameters by simultaneously fitting probe degradation kinetics under different conditions and considers the temporally increasing concentrations of the involved reactive species. It minimizes error propagation and offers insights into the interactions of different species, thereby providing advantages in accuracy, robustness, and interpretability. This study significantly advances the understanding of 3DOM* behavior and provides a valuable kinetic model for aquatic photochemistry research.


Asunto(s)
Materia Orgánica Disuelta , Procesos Fotoquímicos , Fotoquímica , Fotólisis
6.
Ecotoxicol Environ Saf ; 281: 116667, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964068

RESUMEN

Elucidating the absorption and translocation of heavy metal(loid)s by common vegetables across different growth environments and stages is crucial for conducting accurate environmental risk assessments and for associated control. This study investigated temporal variations in the absorption and translocation capacities of pak choi (Brassica rapa L.) for As, Cd, Cr, Cu, Pb, and Zn in polluted soils during the plant growth cycle under greenhouse and open-field cultivation modes. Results showed high root metal(loid) bioconcentration factors and root-to-shoot translocation factors for Cd (0.25 and 1.44, respectively) and Zn (0.26 and 1.01), but low values for As (0.06 and 0.88) and Pb (0.06 and 0.87). The Cd concentration in the aerial edible parts peaked during the early slow growth period, whereas other heavy metal(loid)s peaked during the later stable maturity period. Root bioconcentration and root-to-shoot translocation factors did not significantly differ between cultivation modes. However, greenhouse cultivation exhibited lower average Cd and Zn concentrations in the edible parts and cumulative uptake amounts of most metal(loid)s than open-field cultivation during the typical harvest period spanning days 60 and 90. Short-term transitioning from open-field to greenhouse cultivation may reduce health risks associated with heavy metal(loid) intake via pak choi consumption. These findings facilitate sustainable agricultural practices and food safety management.

7.
Immunology ; 170(4): 567-578, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37688314

RESUMEN

Sepsis is a life-threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin-induced septic mice. However, the effects of Flot2 on sepsis and B-cell immunity remain unknown. Thus, we sorted B cells from Flot2 knockout (Flot2-/- ) mice, RNA-seq revealed significantly upregulated effector B cell (Beff) cytokines such as Il6, Il1b and Cxcl10 after Flot2 deficiency, while it showed no effect on the expression of regulatory B cell (Breg) cytokines such as Il10, Tgfb. Consistently, elevated Beff cytokine IL-6 and unchanged Breg cytokine IL-10 were shown in B cells from Flot2-/- mice. Similar results were subsequently observed in B cell-specific Flot2 knockout chimeric mice. Notably, Flot2 deficiency aggravated sepsis with increased lung injury and shortened survival time in vivo by facilitating Beffs but not Bregs. Taken together, our data identify Flot2 as a novel controller of B cells, Flot2 deficiency amplifies inflammation by affecting Beffs to participate in the pathogenesis and progression of sepsis.


Asunto(s)
Linfocitos B Reguladores , Sepsis , Animales , Ratones , Citocinas/metabolismo , Inflamación/genética
8.
Small ; 19(25): e2208045, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36929607

RESUMEN

Alkaline membrane water electrolysis is a promising production technology, and advanced electrocatalyst and membrane electrode design have always been the core technology. Herein, an ion-exchange method and an environmentally friendly in situ green phosphating strategy are successively employed to fabricate Ru-Ru2 P heterogeneous nanoparticles by using hydroxyapatite (HAP) as a phosphorus source, which is an exceptionally active electrocatalyst for hydrogen evolution reaction (HER). Density functional theory calculation results reveal that strong electronic redistribution occurs at the heterointerface of Ru-Ru2 P, which modulates the electronic structure to achieve an optimized hydrogen adsorption strength. The obtained Ru-Ru2 P possesses excellent HER performance (24 mV at 10 mA cm-2 ) and robust stability (1000 mA cm-2 for 120 h) in alkaline media. Furthermore, an environmentally friendly membrane electrode with a sandwich structure is assembled by HAP nanowires as an alkaline membrane, Ru-Ru2 P as a cathodic catalyst, and NiFe-LDH as an anodic catalyst, respectively. The voltage of (-) Ru-Ru2 P || NiFe-LDH/CNTs (+) (1.53 V at 10 mA cm-2 ) is lower than that of (-) 20 wt% Pt/C || RuO2 (+) (1.60 V at 10 mA cm-2 ) for overall water splitting. Overall, the studies not only design an efficient catalyst but also provide a new route to achieve a high-stability electrolyzer for industrial H2 production.

9.
Chemistry ; 29(54): e202301898, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37501587

RESUMEN

The heavier main group multiple bonds offer an effective tool for small molecule activation. Transient 2H-phosphinidole working as a reactive phosphadiene system undergoes phospha-Diels-Alder reaction with a wide range of non-activated aromatic carbocycles and heterocycles, including naphthalene, anthracene, phenanthrene, furan, thiophene, pyrrole, pyridine, and benzo-fused heterocycles, affording concise access to a range of polycyclic fused rings feature with phosphorus at the bridgehead. These results demonstrate that non-activated (hetero)arenes are capable of acting as 2π systems in [4+2] cycloaddition with highly reactive 2H-phosphindole complex.

10.
Environ Sci Technol ; 57(45): 17291-17301, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37916767

RESUMEN

Heating temperature (HT) during forest fires is a critical factor in regulating the quantity and quality of pyrogenic dissolved organic matter (DOM). However, the temperature thresholds at which maximum amounts of DOM are produced (TTmax) and at which the DOC gain turns into net DOC loss (TT0) remain unidentified on a component-specific basis. Here, based on solid-state 13C nuclear magnetic resonance, absorbance and fluorescence spectroscopies, and Fourier transform ion cyclotron resonance mass spectrometry, we analyzed variations in DOM composition in detritus and soil with HT (150-500 °C) and identified temperature thresholds for components on structural, fluorophoric, and molecular formula levels. TTmax was similar for detritus and soil and ranged between 225 and 250 °C for bulk dissolved organic carbon (DOC) and most DOM components. TT0 was consistently lower in detritus than in soil. Moreover, temperature thresholds differed across the DOM components. As the HT increased, net loss was observed initially in molecular formulas tentatively associated with carbohydrates and aliphatics, then proteins, peptides, and polyphenolics, and ultimately condensed aromatics. Notably, at temperatures lower than TT0, particularly at TTmax, burning increased the DOC quantity and thus might increase labile substrates to fuel soil microbial community. These composition-specific variations of DOM with temperature imply nonlinear and multiple temperature-dependent wildfire impacts on soil organic matter properties.


Asunto(s)
Materia Orgánica Disuelta , Incendios Forestales , Temperatura , Calefacción , Suelo/química
11.
Anim Genet ; 54(4): 553-557, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37040927

RESUMEN

Excreta traits comprise a very important characteristic in breeding that have been neglected for a long time. With the growth of intensive pig farming, plenty of environment problems have been raised, and people have begun to pay attention to pig excreta behaviors from genetics and breeding perspectives. However, the genetic architecture of excreta traits remains unclear. To investigate the genetic architecture of excreta traits in pigs, eight excreta traits and feed conversion ratio (FCR) were analyzed in this study. We performed genome-wide association studies (GWASs) on 213 Yorkshire pigs and estimated genetic parameters for a total number of 290 pigs, comprising 213 Yorkshire, 52 Landrace and 25 Duroc. After analysis, eight and 22 genome-wide significant SNPs were detected for FCR and the eight excreta traits in single-trait GWASs separately, and 18 were detected in a multi-trait meta-analysis for excreta traits, six of which were detected in both the single-trait and the multi-trait GWAS. Eighty, 182 and 133 genes were detected within 1 Mb of the genome-wide significant SNPs for FCR, excreta traits and multi-trait meta-analysis, respectively. Five candidate genes (BCKDC, DBT, ANKRD7, SHPRH and HCRT) with biochemical and physiological effects relevant to feed efficiency and excreta traits might be interesting markers for future breeding. Meanwhile, functional enrichment analysis indicates that most of the significant pathways are associated with the glutathione catabolic process, DNA topological change and replication fork protection complex. This study reveals the architecture of excreta traits in commercial pigs and offers an opportunity for decreasing the pollution from excreta using genomic selection in pigs.


Asunto(s)
Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Porcinos/genética , Animales , Estudio de Asociación del Genoma Completo/veterinaria , Fenotipo , Genómica , Polimorfismo de Nucleótido Simple
12.
Biochem Genet ; 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38095737

RESUMEN

Forest musk deer (Moschus berezovskii) is one of the most endangered medicinally important wild animals in the world. Forest musk deer farming is the main way of production of musk. However, the single provenance and lack of genetic information lead to reduced genetic diversity of forest musk deer. Therefore, more SSR markers need to be developed to identify forest musk deer germplasm. In this study, bone marrow derived mesenchymal cells were used to construct cDNA library for transcriptome sequencing. The datasets were de novo assembled and annotated. 9 polymorphic simple sequence repeat (SSR) markers were finally identified and used to detect population genetic diversity. 6.07 Gb clean data were generated using Illumina sequencing technology, and de novo assembled into 138,591 transcripts and 81,553 unigenes. 5,777 simple sequence repeats (SSRs) were identified, in which there were 578 repeating motif types, with mono-nucleotide and tri-nucleotides comprising 55.88% and 25.60%, respectively. 100 primer pairs were designed to validate amplification and polymorphism using DNA from fecal samples. 9 polymorphic SSRs were developed and used to detect population genetic diversity of 122 forest musk deer in 2 farms. The average number of alleles per locus varied from 4 to 15 (average = 8.3). The observed heterozygosity (HO) per locus ranged from 0.102 to 0.941, while the expected heterozygosity (HE) per locus was from 0.111 to 0.651. All loci deviated significantly from the Hardy-Weinberg equilibrium (p < 0.001). The polymorphism information content (PIC) of these loci varied from 0.108 to 0.619. 9 polymorphic SSR markers were developed in this research. These sites can be used for breeding planning and conservation of germplasm resources.

13.
Ecotoxicol Environ Saf ; 265: 115515, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37774544

RESUMEN

Sunlight exposure can degrade and transform discharged wastewater effluent organic matter (EfOM) in aquatic systems, potentially enhancing the feasibility of reusing wastewater for drinking purposes. However, there remains a lack of comprehensive understanding regarding the sunlight-induced changes in the molecular-level composition, characteristics, and chlorine reactivity of EfOM. Herein, we investigated the impact of sunlight on the optical properties, chemical composition, and formation of disinfection byproducts of EfOM using multiple spectroscopic analyses, high-resolution mass spectrometry, chlorination experiments, and in vitro bioassays. Upon natural sunlight exposure, we observed significant decreases in ultraviolet-visible absorbance and fluorescence intensity of EfOM, indicating the destruction of chromophores and fluorophores. Photolysis generally yields products with lower molecular weight and aromaticity, and with higher saturation and oxidation levels. Moreover, a shift within the EfOM from condensed aromatic-like compounds to tannin-like components was observed. Furthermore, sunlight exposure reduced the reactivity of EfOM toward the formation of trihalomethanes and haloacetonitriles during chlorination, while there was a slight increase in the specific formation potential of haloketones. Importantly, the disinfection byproducts resulting from chlorination of the irradiated EfOM exhibited reduced microtoxicity. Overall, this study provides new insights into alterations in EfOM under sunlight exposure and aids in predicting the health risks of effluent discharge in water environments.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Desinfección/métodos , Aguas Residuales , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Halogenación , Cloro/análisis
14.
Ecotoxicol Environ Saf ; 258: 114998, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37167739

RESUMEN

Triclosan (TCS) is omnipresent in the environment and has drawn increasing attention due to its potential adverse effects on human health. Direct photolysis of TCS readily occurs, especially in the surface layers of waters that receive abundant ultraviolet radiation during the daytime. However, biological concerns and the identification of toxic products during TCS photolysis have been explored limitedly. Therefore, in the present work, the structural characterization of the photolysis products by UVC and UVA were performed based on the mass spectra and fragmental ions. The results displayed that TCS was more readily eliminated by UVC than UVA, and the product species were completely different when TCS was degraded by UVC and UVA, respectively. Two products, m/z 235 and m/z 252, were produced via reductive dechlorination and nucleophilic substitution with UVC, while three dioxin-like isomer products were generated by dechlorination, cyclization and hydroxylation. Furthermore, the results of biological concerns suggested that the elimination of TCS did not represent the disappearance of biological risks. Specifically, more hazardous and photolysis products were formed during TCS photolysis with ultraviolets. For instance, the dioxin-like isomer products were highly microtoxic and genotoxic, and mildly antiestrogenic. The positive findings highlighted the biological concerns of TCS photolysis by ultraviolet radiation in the aquatic environment.


Asunto(s)
Dioxinas , Triclosán , Contaminantes Químicos del Agua , Humanos , Triclosán/metabolismo , Rayos Ultravioleta , Fotólisis , Espectrometría de Masas , Contaminantes Químicos del Agua/análisis
15.
J Obstet Gynaecol Res ; 49(12): 2905-2909, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37813122

RESUMEN

AIM: The prognosis of patients with ovarian cancer with lung metastasis is poor; data on pulmonary metastasectomy for such patients are lacking. This study aimed to determine the safety and feasibility of pulmonary resection as part of cytoreductive surgery for recurrent metastatic ovarian cancer. METHODS: Medical records of patients with ovarian cancer, who underwent pulmonary resection for lung metastasis in our hospital from April 2012 to February 2022, were retrospectively reviewed. RESULTS: Ten patients were included (median age, 53 years). Five patients had metastatic disease limited to the lungs. Additional surgeries included diaphragm resection, partial hepatectomy, para-aortic lymph node dissection, and cytoreduction. We achieved complete cytoreduction for all patients without severe complications, and the 30-day mortality was zero. After a median follow-up of 23 months, four of the patients experienced recurrence. One patient recurred 9 months after the operation and was lost to follow-up at 17 months, two died at 68 and 26 months respectively, one is alive with disease (23 months), and six are alive without recurrence, among whom two have survived for 56 and 124 months. CONCLUSIONS: Pulmonary resection for recurrent metastatic ovarian cancer seems safe and feasible, with long-term survival observed in certain patients. Pulmonary metastasectomy can be performed as part of the debulking surgery for selected patients with relapsed metastatic ovarian cancer. Both the patient lost to follow-up and the one who died at 26 months, had two lung metastatic nodules and did not receive postoperative chemotherapy, which might have led to relatively poor prognosis.


Asunto(s)
Neoplasias Pulmonares , Metastasectomía , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/secundario
16.
Chem Biodivers ; 20(7): e202300424, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37278253

RESUMEN

One new cyclohexenone derivative (1), and two undescribed drimane sesquiterpenes (2 and 3), together with another seven known drimane sesquiterpenes were isolated from a seagrass-derived fungus Aspergillus insuetus SYSU6925. Structures of these metabolites were elucidated by comprehensive spectroscopic analysis, including NMR analysis, mass spectrometry, and ECD calculations. Compounds 1-3, 5 and 7 displayed weak to moderate antifungal activities towards four phytopathogenic fungi, with Minimum inhibition concentration (MIC) values range from 50 to 200 µg/mL. Compound 1, a rare cyclohexenone derivative with n-propyl group exhibited more potent inhibitory activities (MIC, 50 µg/mL) against F. oxysporum than positive control (Triadimefon). Compounds 2 and 3 also exhibit potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in RAW264.7 cells with IC50 values of 21.5±1.1 and 32.6±1.16 µM, respectively.


Asunto(s)
Sesquiterpenos , Hongos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Sesquiterpenos/química , Ciclohexanonas/química
17.
J Am Chem Soc ; 144(38): 17522-17532, 2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-36103720

RESUMEN

Importins are overexpressed in many cancers and mediate the abnormal nuclear transport of oncogenic factors. The druggable potential of importins still remains unclear, largely because of the lack of potent inhibitors. Herein, the anti-castration-resistant prostate cancer (CRPC) screening of a Euphorbiaceae diterpenoid library followed by target fishing led to the identification of a highly potent importin-ß1 inhibitor, daphnane diterpenoid DD1. DD1 selectively inhibited the growth and survival of CRPC cells at subnanomolar concentrations and completely blocked tumor growth in preclinical models at an extremely low dosage. Mechanistic studies revealed that targeting of importin-ß1 by DD1 significantly reduced the nuclear accumulation of key CRPC drivers, shutting down their downstream oncogenic signaling. Disruption of the predicted binding sites of DD1 on importin-ß1 abolished this anti-CRPC effect. These findings suggest that importin-ß1 is an effective therapeutic target in CRPC and that DD1 as the most potent importin-ß1 inhibitor to date can be developed as therapeutics for treatment of this disease.


Asunto(s)
Diterpenos , Neoplasias de la Próstata Resistentes a la Castración , Línea Celular Tumoral , Proliferación Celular , Diterpenos/farmacología , Humanos , Carioferinas/farmacología , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico
18.
J Exp Bot ; 73(1): 50-67, 2022 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-34610119

RESUMEN

Rice polluted by metal(loid)s, especially arsenic (As) and cadmium (Cd), imposes serious health risks. Numerous studies have demonstrated that the obligate plant symbionts arbuscular mycorrhizal fungi (AMF) can reduce As and Cd concentrations in rice. The behaviours of metal(loid)s in the soil-rice-AMF system are of significant interest for scientists in the fields of plant biology, microbiology, agriculture, and environmental science. We review the mechanisms of As and Cd accumulation in rice with and without the involvement of AMF. In the context of the soil-rice-AMF system, we assess and discuss the role of AMF in affecting soil ion mobility, chemical forms, transport pathways (including the symplast and apoplast), and genotype variation. A potential strategy for AMF application in rice fields is considered, followed by future research directions to improve theoretical understanding and encourage field application.


Asunto(s)
Arsénico , Micorrizas , Oryza , Contaminantes del Suelo , Cadmio/análisis , Hongos , Raíces de Plantas/química , Suelo , Microbiología del Suelo
19.
Pharmacol Res ; 178: 106160, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35259480

RESUMEN

Small cell lung cancer (SCLC) is an aggressive and exceptionally fatal disease. Unlike non- small cell lung cancer (NSCLC), no targetable genetic driver events have been identified in SCLC to date. Here, we investigate the function of RAR-related orphan receptor gamma (RORγ) and identified the anti-cancer activity of its natural inhibitor against SCLC and illustrate the underlying mechanism. We show that RORγ depletion affected cell growth both in 2-D cell proliferation and 3-D organoids formation. Natural marine product N-hydroxyapiosporamide (N-hydap) directly bound to RORγ and inhibited its transcriptional activity, leading to the blocking of transmission process of RORγ signaling. Gene expression profiling analysis revealed that N-hydap reprograms neuroendocrine fate via inhibiting RORγ activity in SCLC. Chromatin immunoprecipitation analysis showed that N-hydap strongly reduced RORγ occupancy and transcriptional activation-linked histone marks H3K27ac on the promoter and/or enhancer sites of neurogenesis markers gene including aurora kinase a (AURKA), delta like canonical Notch ligand 3 (DLL3) and tubulin beta 3 class III (TUBB3). Therapeutically, N-hydap exhibited a strong inhibitory effect on tumor growth and did not show significant toxicity in SCLC mice xenograft models. Taken together, RORγ could be an attractive target for SCLC and thus N-hydap can be a promising therapeutic drug candidate for SCLC by inhibiting the RORγ activation.


Asunto(s)
Productos Biológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Animales , Productos Biológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas de la Membrana/metabolismo , Ratones , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología
20.
Environ Sci Technol ; 56(17): 12678-12687, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-35947441

RESUMEN

High-intensity wildfires alter the chemical composition of organic matter, which is expected to be distinctly different from low-intensity prescribed fires. Herein, we used pyrolysis gas chromatography/mass spectrometry (Py-GC/MS), in conjunction with solid-state 13C nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy, to assess chemical alterations from three wildfires and a long-term frequent prescribed fire site. Our results showed that black ash formed under moderate intensity burns contained less aromatic (ArH), polyaromatic hydrocarbon (PAH), and nitrogen-containing compounds (Ntg) but more lignin (LgC) and phenol compounds (PhC), compared to white ash formed under high intensity burns. Both 13C NMR and FT-IR confirmed a higher relative percentage of carboxyl carbon in white ash, indicating the potential for higher water solubility and more mobile carbon, relative to black ash. Compared to wildfires, ash from low-intensity prescribed fire contained less ArH, PAH, and Ntg and more LgC and PhC. Controlled laboratory burning trials indicated that organic matter alteration was sensitive to the burn temperature, but not related to the fuel type (pine vs fir) nor oxygen absence/presence at high burn temperatures. This study concludes that higher burn temperatures resulted in higher (poly)aromatic carbon/nitrogen and lower lignin/phenol compounds.


Asunto(s)
Quemaduras , Incendios , Carbono/análisis , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lignina , Nitrógeno/análisis , Fenoles , Pirólisis , Espectroscopía Infrarroja por Transformada de Fourier
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