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1.
Metabolism ; 145: 155631, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37330135

RESUMEN

BACKGROUND: The SREBP/SCAP/INSIG complex plays an essential role in SREBP activation and de novo lipogenesis. Whether the activation process is affected by hydroxysteroid 17-beta dehydrogenase 6 (HSD17B6) remains unknown. METHODS: SREBP's transcriptional activities were analyzed using an SRE-luciferase (SRE-luc) reporter in 293T cells, Huh7 hepatoma cells, and primary human hepatocytes following a variety of conditions, including ectopic expression of HSD17B6, HSD17B6 mutants defective in its enzymatic activities, knockdown of HSD17B6, and cholesterol starvation. The interaction between HSD17B6 and SREBP/SCAP/INSIG complex was analyzed in 293T cells, Huh7 cells and mouse liver upon ectopic expression of HSD17B6 and its mutants; the interaction was also analyzed using endogenous proteins. The impacts of HSD17B6 on SREBP target expression, glucose tolerance, diet-induced obesity, and type 2 diabetes (T2D) were examined using Huh7 cells in vitro, and with C57BL/6 and NONcNZO10/LtJ T2D mice in vivo. RESULTS: HSD17B6 binds to the SREBP/SCAP/INSIG complex and inhibits SREBP signaling in cultured hepatocytes and mouse liver. Although HSD17B6 plays a role in maintaining the equilibrium of 5α-dihydrotestosterone (DHT) in the prostate, a mutant defective in androgen metabolism was as effective as HSD17B6 in inhibiting SREBP signaling. Hepatic expression of both HSD17B6 and the defective mutant improved glucose intolerance and reduced hepatic triglyceride content in diet-induced obese C57BL/6 mice, while hepatic knockdown of HSD17B6 exacerbated glucose intolerance. Consistent with these results, liver-specific expression of HSD17B6 in a polygenic NONcNZO10/LtJ T2D mice reduced T2D development. CONCLUSIONS: Our study unveils a novel role of HSD17B6 in inhibiting SREBP maturation via binding to the SREBP/SCAP/INSIG complex; this activity is independent of HSD17B6's sterol oxidase activity. Through this action, HSD17B6 improves glucose tolerance and attenuates the development of obesity-induced T2D. These findings position HSD17B6 as a potential therapeutic target for T2D therapy.


Asunto(s)
Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Masculino , Ratones , Humanos , Animales , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Diabetes Mellitus Tipo 2/genética , Péptidos y Proteínas de Señalización Intracelular , Ratones Endogámicos C57BL , Obesidad , Glucosa , Racemasas y Epimerasas
2.
Sci Total Environ ; 890: 164070, 2023 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-37196949

RESUMEN

For three years, a large amount of manufactured pollutants such as plastics, antibiotics and disinfectants has been released into the environment due to COVID-19. The accumulation of these pollutants in the environment has exacerbated the damage to the soil system. However, since the epidemic outbreak, the focus of researchers and public attention has consistently been on human health. It is noteworthy that studies conducted in conjunction with soil pollution and COVID-19 represent only 4 % of all COVID-19 studies. In order to enhance researchers' and the public awareness of the seriousness on the COVID-19 derived soil pollution, we propose the viewpoint that "pandemic COVID-19 ends but soil pollution increases" and recommend a whole-cell biosensor based new method to assess the environmental risk of COVID-19 derived pollutants. This approach is expected to provide a new way for environmental risk assessment of soils affected by contaminants produced from the pandemic.


Asunto(s)
COVID-19 , Contaminantes Ambientales , Humanos , COVID-19/epidemiología , Pandemias , Contaminación Ambiental/análisis , Suelo , Plásticos , Medición de Riesgo
3.
Artículo en Inglés | MEDLINE | ID: mdl-36767042

RESUMEN

Water contaminated with emerging pollutants has become a serious environmental issue globally. Biochar is a porous and carbon-rich material produced from biomass pyrolysis and has the potential to be used as an integrated adsorptive material. Many studies have shown that biochar is capable to adsorb emerging pollutants from aquatic systems and could be used to solve the water pollution problem. Here, we provided a dual perspective on removing emerging pollutants from aquatic systems using biochar and analyzed the emerging pollutant removal efficiency from the aspects of biochar types, pollutant types and coexistence with heavy metals, as well as the associated mechanisms. The potential risks and future research directions of biochar utilization are also presented. This review aims to assist researchers interested in using biochar for emerging pollutants remediation in aquatic systems and facilitate research on emerging pollutants removal, thereby reducing their environmental risk.


Asunto(s)
Contaminantes Ambientales , Metales Pesados , Contaminantes del Suelo , Carbón Orgánico , Contaminación Ambiental , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Suelo
4.
Environ Pollut ; 310: 119879, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35931389

RESUMEN

Heavy metal contamination and low use efficiency of phosphorus (P) fertilizers are worldwide issues. Alkaline lignin is expected to decrease the heavy metal risk and enhance the P availability in heavy-metal-contaminated soils. A 120-day incubation study examined the effects of alkaline lignin on Cd, Pb and P bioavailability and transformation in Cd or Cd/Pb co-contaminated red and cinnamon soils and elucidated the associated mechanisms. A pot experiment further tested Cd accumulation in lettuce (Lactuca sativa L.) grown in the Cd-contaminated red soil. The amendment of alkaline lignin increased the concentrations of bioavailable Cd by 13-20% in the acid red soil and 97-107% in the alkaline cinnamon soil, respectively, due to the increase of dissolved organic C concentrations. Meanwhile, it also increased the concentrations of available P in both soils, Al-P in the red soil and Ca2-P in the cinnamon soil. Consequently, alkaline lignin amendment increased lettuce biomass of shoots by 8-23% and of roots by 56-71%, P uptake by 37-50% in shoots and by 28-62% in roots, and limited Cd transport from root to shoot which decreased Cd concentrations by 26% in lettuce shoot (edible part). The results suggest that alkaline lignin increases plant growth and decreases Cd bioaccumulation in the shoot through restricting Cd translocation from the root to shoot and increasing soil P availability but not Cd immobilization, and hence may have potential to reduce vegetable Cd contamination risk.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Cadmio , Plomo , Lactuca , Lignina , Suelo
5.
PLoS One ; 17(4): e0264799, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35482762

RESUMEN

MafB (a bZIP transcription factor), ß-catenin (the ultimate target of the Wnt signal transduction pathway that acts as a transcriptional co-activator of LEF/TCF proteins), and WDR77 (a transcriptional co-activator of multiple hormone receptors) are important for breast cellular transformation. Unexpectedly, these proteins interact directly with each other, and they have similar genomic binding profiles. Furthermore, while some of these common target sites coincide with those bound by LEF/TCF, the majority are located just downstream of transcription initiation sites at a position near paused RNA polymerase (Pol II) and the +1 nucleosome. Occupancy levels of these factors at these promoter-proximal sites are strongly correlated with the level of paused Pol II and transcriptional activity.


Asunto(s)
Cateninas , beta Catenina , Cateninas/metabolismo , Regiones Promotoras Genéticas , ARN Polimerasa II/metabolismo , Factores de Transcripción/metabolismo , Vía de Señalización Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
6.
Cell Rep ; 37(5): 109955, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34731634

RESUMEN

Macrophages undergoing M1- versus M2-type polarization differ significantly in their cell metabolism and cellular functions. Here, global quantitative time-course proteomics and phosphoproteomics paired with transcriptomics provide a comprehensive characterization of temporal changes in cell metabolism, cellular functions, and signaling pathways that occur during the induction phase of M1- versus M2-type polarization. Significant differences in, especially, metabolic pathways are observed, including changes in glucose metabolism, glycosaminoglycan metabolism, and retinoic acid signaling. Kinase-enrichment analysis shows activation patterns of specific kinases that are distinct in M1- versus M2-type polarization. M2-type polarization inhibitor drug screens identify drugs that selectively block M2- but not M1-type polarization, including mitogen-activated protein kinase kinase (MEK) and histone deacetylase (HDAC) inhibitors. These datasets provide a comprehensive resource to identify specific signaling and metabolic pathways that are critical for macrophage polarization. In a proof-of-principle approach, we use these datasets to show that MEK signaling is required for M2-type polarization by promoting peroxisome proliferator-activated receptor-γ (PPARγ)-induced retinoic acid signaling.


Asunto(s)
Inhibidores de Histona Desacetilasas/farmacología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteoma , Proteómica , Animales , Metabolismo Energético , Humanos , Interleucina-4/farmacología , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , PPAR gamma/agonistas , PPAR gamma/metabolismo , Fenotipo , Fosforilación , Prueba de Estudio Conceptual , Transducción de Señal , Células THP-1 , Factores de Tiempo , Tretinoina/farmacología
7.
Cancers (Basel) ; 13(17)2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34503297

RESUMEN

Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC. The current understanding and management of pRCC remain poor. We report here OIP5 being a novel oncogenic factor and possessing robust prognostic values and therapeutic potential. OIP5 upregulation is observed in pRCC. The upregulation is associated with pRCC adverse features (T1P < T2P < CIMP, Stage1 + 2 < Stage 3 < Stage 4, and N0 < N1) and effectively stratifies the fatality risk. OIP5 promotes ACHN pRCC cell proliferation and xenograft formation; the latter is correlated with network alterations related to immune regulation, metabolism, and hypoxia. A set of differentially expressed genes (DEFs) was derived from ACHN OIP5 xenografts and primary pRCCs (n = 282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (p < 2 × 10-16) and relapse (p < 2 × 10-16) possibilities. High-risk tumors stratified by Overlap66 risk score possess an immune suppressive environment, evident by elevations in Treg cells and PD1 in CD8 T cells. Upregulation of PLK1 occurs in both xenografts and primary pRCC tumors with OIP5 elevations. PLK1 displays a synthetic lethality relationship with OIP5. PLK1 inhibitor BI2356 inhibits the growth of xenografts formed by ACHN OIP5 cells. Collectively, the OIP5 network can be explored for personalized therapies in management of pRCC patients.

8.
Elife ; 102021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34463254

RESUMEN

The YAP and TAZ paralogs are transcriptional co-activators recruited to target sites by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB (a member of the AP-1 family) and STAT3, key transcription factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, and they stimulate transcriptional activation by AP-1 proteins. JUNB, STAT3, and TEAD co-localize at virtually all YAP/TAZ target sites, yet many target sites only contain individual AP-1, TEAD, or STAT3 motifs. This observation and differences in relative crosslinking efficiencies of JUNB, TEAD, and STAT3 at YAP/TAZ target sites suggest that YAP/TAZ is recruited by different forms of an AP-1/STAT3/TEAD complex depending on the recruiting motif. The different classes of YAP/TAZ target sites are associated with largely non-overlapping genes with distinct functions. A small minority of target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes from shared YAP/TAZ target sites. Genes containing either the AP-1 or TEAD class of YAP/TAZ sites are associated with poor survival of breast cancer patients with the triple-negative form of the disease.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Transformación Celular Neoplásica/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción AP-1/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional , Neoplasias de la Mama Triple Negativas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Factor de Transcripción STAT3/genética , Transducción de Señal , Factor de Transcripción AP-1/genética , Factores de Transcripción/genética , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Proteínas Señalizadoras YAP
9.
Chemosphere ; 281: 130969, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34289623

RESUMEN

Lignin is a low-cost and environmental-friendly material and could increase the solubility of phosphorus (P) in soils. Meanwhile, application of P compounds to soils decreases the bioavailability of heavy metals. However, there are few reports on whether lignin-induced P release immobilizes heavy metals in soil. This study investigated this possibility by adding alkaline lignin to forest, paddy and upland soils differing in pH and available P. The amendment of alkaline lignin increased soil P availability and enhanced the adsorption and decreased the desorption percentages of Cd in acid forest and paddy soils. The P released from the soil could immobilize Pb and Cd but the presence of Pb decreased the adsorption capacity of Cd on the acid soils. In comparison, the alkaline lignin decreased Cd adsorption and raised Cd desorption in the alkaline upland soil, due to the formation of soluble complex of hydrophilic organic matter with Cd. In addition, precipitation, complexion, and competition effect among Cd, P and lignin in different soils led to various P concentrations in the experiment. The study suggests that alkaline lignin was effective in Cd/Pb immobilization partly via enhanced P availability in acid soils, but was ineffective in Cd immobilization in alkaline soils.


Asunto(s)
Contaminantes del Suelo , Suelo , Cadmio/análisis , Plomo , Lignina , Contaminantes del Suelo/análisis
10.
Ecotoxicol Environ Saf ; 209: 111840, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33383343

RESUMEN

Heavy-metal contamination is widespread in agricultural soils worldwide, especially paddy soils contaminated by Cd. Amendment-induced immobilization of heavy metals is an attractive and effective technique, provided that cost-effective materials are used. This field experiment compared three alkaline passivators (attapulgite, processed oyster shell powder, and mixed soil conditioner) at a rate of 2.25 t ha-1 for their effectiveness in decreasing Cd bioavailability in soils and accumulation in rice plants in a paddy field contaminated by Cd (0.38 Cd mg kg-1). The utilization of attapulgite and processed oyster shell powder decreased labile fractions but increased stable fractions of Cd in soils through ion exchange, precipitation and complexation. The addition of attapulgite decreased the concentration of bioavailable Cd in both bulk and rhizosphere soils, whereas the amendment of processed oyster shell powder decreased it only in bulk soil. The Cd accumulation in rice plants correlated significantly with acid-soluble and residual Cd fractions in the rhizosphere soil but not in the bulk soil. The addition of attapulgite and processed oyster shell powder decreased Cd accumulation in rice grains from 0.26 mg kg-1 to 0.14 and 0.19 mg kg-1, respectively, meeting the National Food Safety Standard (< 0.20 mg kg-1). However, the mixed soil conditioner did not decrease the Cd accumulation in rice shoots or grains. This study demonstrated that attapulgite and processed oyster shell powder were economic agents in reducing Cd accumulation in rice grains.


Asunto(s)
Cadmio/metabolismo , Restauración y Remediación Ambiental/métodos , Compuestos de Magnesio , Oryza/metabolismo , Compuestos de Silicona , Contaminantes del Suelo/metabolismo , Ácidos , Agricultura , Exoesqueleto/química , Animales , Disponibilidad Biológica , Cadmio/análisis , Carbonato de Calcio , Ostreidae , Polvos , Rizosfera , Suelo , Contaminantes del Suelo/análisis
11.
Water Sci Technol ; 82(8): 1643-1652, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33107858

RESUMEN

The sewage sludge production has been increasing along with the ever-growing populations and wastewater treatment rate. Lanthanum-doped activated carbon (AC-La) was derived from municipal sludge via chemical activation and utilized for fluoride removal. Batch experiments were conducted to discuss the effect of lanthanum dosage, time and pH on the adsorption process. The results showed that 4 g/L AC-La exhibited a fluoride removal rate of 80.9% with 10 mg/L initial fluoride concentration, and the optimal pH range for adsorption was 3-10. X-ray fluorescence, scanning electron microscopy with energy-dispersive X-ray spectroscopy, Brunauer-Emmett-Teller, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses were conducted to analyze the microstructure and chemical properties of sludge, unmodified activated carbon (AC) and AC-La. The results showed that with initial lanthanum dosage of 15 wt%, the final loading amount of La in AC-La was 13.8 wt%. After modification, the specific surface area of AC-La increased from 1.8 m2/g (sludge) to 133.0 m2/g. The removal mechanism of fluoride onto AC-La was mainly the inner-sphere complexation between lanthanum and fluoride, facilitated by exchange interaction with hydroxyls. A stability study showed that AC-La maintained a quite small dissolution and was safe in waters (La dissolution rate < 0.2‰).


Asunto(s)
Lantano , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico , Cinética , Aguas del Alcantarillado , Espectroscopía Infrarroja por Transformada de Fourier
12.
J Environ Manage ; 249: 109342, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31400588

RESUMEN

In view of the circulation cooling water (CCW) quality for refining and petrochemical enterprises, distillates obtained from shale gas produced water after alkali precipitation, filtration and multi-effect evaporation required further purification to remove NH3-N and COD. Illumination, adsorption, photocatalysis after adsorption equilibrium (AP) and integration of adsorption and photocatalysis (IOAP) were carried out to optimize the distillates treatment. AP and IOAP treatments were feasible for the simultaneous removal of NH3-N and COD from the target distillate, while IOAP treatment had much better adaptability and practicability due to its economic cost and easy operation. In IOAP, the removal rate of COD and NH3-N was high up to 59.0% and 88.9%, respectively, under Xenon lamp illumination (25 A) for 60 min with 10 g/L zeolite. The residual concentration of COD and NH3-N were 73.9 mg/L and 23.0 mg/L, respectively, which could well meet the CCW quality. Furthermore, the results of zeolites characterization (SEM-EDX, BET and FTIR) and kinetics analysis showed that the removal of COD in IOAP process mainly depended on the effect of photocatalysis excited by zeolite, while the removal of NH3-N was in virtue of the synergistic effect of photocatalysis and adsorption.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Zeolitas , Adsorción , Catálisis , Gas Natural
13.
Sci Total Environ ; 688: 818-826, 2019 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-31255820

RESUMEN

Cd contamination in agricultural soils threatens the safety of agricultural products and poses human health risk via food chain. However, the remediation of Cd polluted alkaline soils has not drawn the public concern, and the corresponding efficient amendments that can reduce Cd accumulation in crop grains are relatively few. In current study, mercapto-modified attapulgite (MA in abbreviation) was selected as the amendment to conduct winter wheat (Triticum aestivum L.) cultivation pot experiment to investigate the effect of MA on Cd accumulation in winter wheat and Cd bioavailability in alkaline soil. MA had no adverse impact on the normal growth of winter wheat but could inhibit Cd accumulation in wheat grain of both cultivars grown in alkaline soil with a maximum reduction of 75%, while pH-regulating amendment sepiolite had no reduction effect. In the term of soil chemistry, MA could decrease the zeta potential of soil particles and enhance the sorption amount of Cd on soil particles, resulted in the increase of Fe-Mn-oxides bounded Cd fraction in alkaline soil. The enhanced sorption effect combined with complexation effect of MA itself, made the exchangeable and bioavailable Cd concentrations in the soil decrease. In the term of plant uptake, MA could inhibit the uptake of Cd via roots from the soil, and hinder Cd transfer from roots to grains. MA had environmental friendliness and capability in the aspect of soil pH, effective cation exchange capacity and available micronutrients in the soil. The high performance of MA in inhabitation of Cd in winter wheat revealed that it was an efficient immobilization agent with great application potential for Cd-polluted alkaline soil.


Asunto(s)
Cadmio/metabolismo , Restauración y Remediación Ambiental/métodos , Compuestos de Magnesio , Compuestos de Silicona , Contaminantes del Suelo/metabolismo , Triticum/metabolismo , Suelo/química
14.
Ther Adv Med Oncol ; 11: 1758835919846372, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31205500

RESUMEN

BACKGROUND: The aim of this study was to investigate the contributions of FAM84B in prostate tumorigenesis and progression. METHODS: A FAM84B mutant with deletion of its HRASLS domain (ΔHRASLS) was constructed. DU145 prostate cancer (PC) cells stably expressing an empty vector (EV), FAM84B, or FAM84B (ΔHRASLS) were produced. These lines were examined for proliferation, invasion, and growth in soft agar in vitro. DU145 EV and FAM84B cells were investigated for tumor growth and lung metastasis in NOD/SCID mice. The transcriptome of DU145 EV xenografts (n = 2) and DU145 FAM84B tumors (n = 2) was determined using RNA sequencing, and analyzed for pathway alterations. The FAM84B-affected network was evaluated for an association with PC recurrence. RESULTS: FAM84B but not FAM84B (ΔHRASLS) increased DU145 cell invasion and growth in soft agar. Co-immunoprecipitation and co-localization analyses revealed an interaction between FAM84B and FAM84B (ΔHRASLS), suggesting an intramolecular association among FAM84B molecules. FAM84B significantly enhanced DU145 cell-derived xenografts and lung metastasis. In comparison with DU145 EV cell-produced tumors, those generated by DU145 FAM84B cells showed a large number of differentially expressed genes (DEGs; n = 4976). A total of 51 pathways were enriched in these DEGs, which function in the Golgi-to-endoplasmic reticulum processes, cell cycle checkpoints, mitochondrial events, and protein translation. A novel 27-gene signature (SigFAM) was derived from these DEGs; SigFAM robustly stratifies PC recurrence in two large PC populations (n = 490, p = 0; n = 140, p = 4e-11), and remains an independent risk factor of PC recurrence after adjusting for age at diagnosis, Gleason scores, surgical margin, and tumor stages. CONCLUSIONS: FAM84B promotes prostate tumorigenesis through a complex network that predicts PC recurrence.

15.
Environ Pollut ; 252(Pt A): 846-855, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31202137

RESUMEN

There are global concerns about heavy metal (HM) contamination in soils, which in turn has produced an increased demand for soil remediation. Biochar has been widely documented to effectively immobilize metals in contaminated soils and has received increasing attention for use in soil remediation. Here, we review recent progresses in understanding metal-biochar interactions in soils, potential risks associated with biochar amendment, and application of biochar in soil remediation in China. These recent studies indicate that: (1) the remediation effect depends on the characteristics of both biochar and soil and their interactions; (2) biochar applications could decrease the mobility/bioavailability of HMs in soils and HM accumulation in plants; and (3) despite its advantages, biochar applications could pose ecological and health risks, e.g., by releasing toxic substances into soils or by inhalation of biochar dust. Research gaps still exist in the development of practical methods for preparing and applying different biochars that target specific HMs. In the future, the long term effects and security of biochar applications on soil remediation, soil organisms and plant growth need to be considered.


Asunto(s)
Carbón Orgánico/química , Contaminación Ambiental/análisis , Restauración y Remediación Ambiental/métodos , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Disponibilidad Biológica , China , Plantas , Suelo/química
16.
Proc Natl Acad Sci U S A ; 116(19): 9453-9462, 2019 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-30910960

RESUMEN

Using an inducible, inflammatory model of breast cellular transformation, we describe the transcriptional regulatory network mediated by STAT3, NF-κB, and AP-1 factors on a genomic scale. These proinflammatory regulators form transcriptional complexes that directly regulate the expression of hundreds of genes in oncogenic pathways via a positive feedback loop. This transcriptional feedback loop and associated network functions to various extents in many types of cancer cells and patient tumors, and it is the basis for a cancer inflammation index that defines cancer types by functional criteria. We identify a network of noninflammatory genes whose expression is well correlated with the cancer inflammatory index. Conversely, the cancer inflammation index is negatively correlated with the expression of genes involved in DNA metabolism, and transformation is associated with genome instability. We identify drugs whose efficacy in cell lines is correlated with the cancer inflammation index, suggesting the possibility of using this index for personalized cancer therapy. Inflammatory tumors are preferentially associated with infiltrating immune cells that might be recruited to the site of the tumor via inflammatory molecules produced by the cancer cells.


Asunto(s)
ADN de Neoplasias/metabolismo , Regulación Neoplásica de la Expresión Génica , FN-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción AP-1/metabolismo , Línea Celular Tumoral , ADN de Neoplasias/genética , Humanos , Inflamación , FN-kappa B/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patología , Factor de Transcripción STAT3/genética , Factor de Transcripción AP-1/genética
17.
Artículo en Inglés | MEDLINE | ID: mdl-30781834

RESUMEN

Xiangtan, South China, is characterized by year-round high relative humidity and very low wind speeds. To assess levels of PM2.5, daily samples were collected from 2016 to 2017 at two urban sites. The mass concentrations of PM2.5 were in the range of 30⁻217 µg/m³, with the highest concentrations in winter and the lowest in spring. Major water-soluble ions (WSIIs) and total carbon (TC) accounted for 58⁻59% and 21⁻24% of the PM2.5 mass, respectively. Secondary inorganic ions (SO42-, NO3-, and NH4⁺) dominated the WSIIs and accounted for 73% and 74% at the two sites. The concentrations of K, Fe, Al, Sb, Ca, Zn, Mg, Pb, Ba, As, and Mn in the PM2.5 at the two sites were higher than 40 ng/m³, and decreased in the order of winter > autumn > spring. Enrichment factor analysis indicates that Co, Cu, Zn, As, Se, Cd, Sb, Tl, and Pb mainly originates from anthropogenic sources. Source apportionment analysis showed that secondary inorganic aerosols, vehicle exhaust, coal combustion and secondary aerosols, fugitive dust, industrial emissions, steel industry are the major sources of PM2.5, contributing 25⁻27%, 21⁻22%, 19⁻21%, 16⁻18%, 6⁻9%, and 8⁻9% to PM2.5 mass.


Asunto(s)
Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Carbono/análisis , China , Ciudades , Monitoreo del Ambiente , Iones/análisis , Tamaño de la Partícula , Estaciones del Año , Tiempo (Meteorología)
18.
Mol Oncol ; 12(9): 1559-1578, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30024105

RESUMEN

We report here numerous novel genes and multiple new signatures which robustly predict prostate cancer (PC) recurrence. We extracted 696 differentially expressed genes relative to a reported PC signature from the TCGA dataset (n = 492) and built a 15-gene signature (SigMuc1NW) using Elastic-net with 10-fold cross-validation through analyzing their expressions at 1.5 standard deviation/SD below and 2 SD above a population mean. SigMuc1NW predicts biochemical recurrence (BCR) following surgery with 56.4% sensitivity, 72.6% specificity, and 63.24 median months disease free (MMDF) (P = 1.12e-12). The prediction accuracy is improved with the use of SigMuc1NW's cutpoint (P = 3e-15) and is further enhanced (sensitivity 67%, specificity 75.7%, MMDF 45.2, P = 0) when all 15 genes were analyzed through their cutpoints instead of their SDs. These genes individually associate with BCR using either SD or cutpoint as the cutoff points. Eight of 15 genes are individual risk factors after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. Eleven of 15 genes are novel to PC. SigMuc1NW discriminates BCR with time-dependent AUC (tAUC) values of 76.6% at 11.5 months (76.6%-11.5 m), 73.8%-22.3 m, 78.5%-32.1 m, and 76.4%-48.4 m. SigMuc1NW is correlated with adverse features of PC, high Gleason scores (odds ratio/OR 1.48, P < 2e-16), and advanced tumor stages (OR 1.33, P = 4.37e-13). SigMuc1NW remains an independent risk factor of BCR (HR 2.44, 95% CI 1.53-3.87, P = 1.62e-4) after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. In an independent PC (MSKCC) cohort (n = 140), these 15 genes were altered in PC vs normal tissue, metastatic PCs vs primary PCs, and recurrent PCs vs nonrecurrent PCs. Importantly, a 10-gene subsignature SigMuc1NW1 predicts BCR in MSKCC (P = 3.11e-15) and TCGA (P = 3.13e-12); SigMuc1NW1 discriminates BCR at 18.4 m with tAUC as 82.5%. Collectively, our analyses support SigMuc1NW as a novel and robust signature in predicting BCR of PC.


Asunto(s)
Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/genética , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Transcriptoma , Estudios de Cohortes , Minería de Datos , Bases de Datos Genéticas , Supervivencia sin Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Prostatectomía/efectos adversos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Factores de Riesgo
19.
Sci Total Environ ; 625: 987-993, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29996465

RESUMEN

In recent years, biochar has been extensively studied as a sorbent for immobilizing contaminants and minimizing their bioavailability in soils. Few studies have been conducted to evaluate the interactions between biochar and compost in soils and their impact on degradation of organic contaminants. In the present study, soils with high organic carbon content (HOC) and low organic carbon content (LOC) were spiked with 100mg·kg-1 di-(2-ethylhexyl) phthalate (DEHP) amended with biochar derived from dead pigs, bamboo, and composted sheep manure. The soils were thereafter incubated for 112days at 25°C and periodically sampled for monitoring DEHP concentrations. Degradation of DEHP was described by a logistic model. Results showed that the initial degradation rates were slow, but accelerated after 14days of incubation. The DEHP degradation rates were higher in the HOC soils than in the LOC soils over the incubation period. The half-lives of DEHP were shorter in the LOC soils treated with pig biochar, and bamboo/pig biochar plus compost than in the untreated soil. However, there was no significant difference in the half-lives of DEHP in the HOC control and treated soils. The differential effects of soil amendments on DEHP degradation between LOC and HOC soils could be explained by the properties of the organic amendments, soil pH and the organic carbon contents of the soils.

20.
Nat Commun ; 9(1): 2068, 2018 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-29802342

RESUMEN

Transient activation of Src oncoprotein in non-transformed, breast epithelial cells can initiate an epigenetic switch to the stably transformed state via a positive feedback loop that involves the inflammatory transcription factors STAT3 and NF-κB. Here, we develop an experimental and computational pipeline that includes 1) a Bayesian network model (AccessTF) that accurately predicts protein-bound DNA sequence motifs based on chromatin accessibility, and 2) a scoring system (TFScore) that rank-orders transcription factors as candidates for being important for a biological process. Genetic experiments validate TFScore and suggest that more than 40 transcription factors contribute to the oncogenic state in this model. Interestingly, individual depletion of several of these factors results in similar transcriptional profiles, indicating that a complex and interconnected transcriptional network promotes a stable oncogenic state. The combined experimental and computational pipeline represents a general approach to comprehensively identify transcriptional regulators important for a biological process.


Asunto(s)
Neoplasias de la Mama/genética , Transformación Celular Neoplásica/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica/genética , Factores de Transcripción/metabolismo , Mama/citología , Mama/patología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/genética , Genoma Humano/genética , Humanos , Modelos Genéticos , Factores de Transcripción/genética
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