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1.
Biochar ; 6(1): 52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799721

RESUMO

While many studies have examined the role of biochar in carbon (C) accrual in short-term scale, few have explored the decadal scale influences of biochar on non-biochar C, e.g., native soil organic C (SOC) and added substrate. To address this knowledge gap, soils were collected from decade-old biochar field trials located in the United Kingdom (Cambisol) and China (Fluvisol), with each site having had three application rates (25-30, 50-60 and 75-100 Mg ha-1) of biochar plus an unamended Control, applied once in 2009. We assessed physicochemical and microbial properties associated with sucrose (representing the rhizodeposits) mineralization and the priming effect (PE) on native SOC. Here, we showed both soils amended with biochar at the middle application rate (50 Mg ha-1 biochar in Cambisol and 60 Mg ha-1 biochar in Fluvisol) resulted in greater substrate mineralization. The enhanced accessibility and availability of sucrose to microorganisms, particularly fast-growing bacterial genera like Arenimonas, Spingomonas, and Paenibacillus (r-strategists belonging to the Proteobacteria and Firmicutes phyla, respectively), can be attributed to the improved physicochemical properties of the soil, including pH, porosity, and pore connectivity, as revealed by synchrotron-based micro-CT. Random forest analysis also confirmed the contribution of the microbial diversity and physical properties such as porosity on sucrose mineralization. Biochar at the middle application rate, however, resulted in the lowest PE (0.3 and 0.4 mg of CO2-C g soil-1 in Cambisol and Fluvisol, respectively) after 53 days of incubation. This result might be associated with the fact that the biochar promoted large aggregates formation, which enclosed native SOC in soil macro-aggregates (2-0.25 mm). Our study revealed a diverging pattern between substrate mineralization and SOC priming linked to the biochar application rate. This suggests distinct mechanisms, biophysical and physicochemical, driving the mineralization of non-biochar carbon in a field where biochar was applied a decade before. Supplementary Information: The online version contains supplementary material available at 10.1007/s42773-024-00327-0.

2.
Nat Commun ; 14(1): 8517, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129441

RESUMO

Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.


Assuntos
Estudo de Associação Genômica Ampla , Placenta , Adulto , Humanos , Feminino , Gravidez , Placenta/metabolismo , Encurtamento do Telômero , Telômero/genética , Perfilação da Expressão Gênica
3.
Cell Commun Signal ; 21(1): 353, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38098027

RESUMO

Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development, tissue repair, and tumorigenesis. At the maternal-fetal interface, emerging evidence underscores the importance of precisely regulated YAP activity in ensuring successful pregnancy initiation and progression. However, despite the established association between YAP dysregulation and adverse pregnancy outcomes, insights into the impact of aberrant YAP levels in fetal-derived, particularly trophoblast cells, and the ensuing dysfunction at the maternal-fetal interface remain limited. This review comprehensively examines YAP expression and its regulatory mechanisms in trophoblast cells throughout pregnancy. We emphasize its integral role in placental development and maternal-fetal interactions and delve into the correlations between YAP dysregulation and pregnancy complications. A nuanced understanding of YAP's functions during pregnancy could illuminate intricate molecular mechanisms and pave the way for innovative prevention and treatment strategies for pregnancy complications. Video Abstract.


Assuntos
Placenta , Complicações na Gravidez , Gravidez , Feminino , Humanos , Placenta/metabolismo , Trofoblastos/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Complicações na Gravidez/metabolismo
4.
Environ Sci Technol ; 57(4): 1837-1847, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36594827

RESUMO

Biochar amendments add persistent organic carbon to soil and can stabilize rhizodeposits and existing soil organic carbon (SOC), but effects of biochar on subsoil carbon stocks have been overlooked. We quantified changes in soil inorganic carbon (SIC) and SOC to 2 m depth 10 years after biochar application to calcareous soil. The total soil carbon (i.e., existing SOC, SIC, and biochar-C) increased by 71, 182, and 210% for B30, B60, and B90, respectively. Biochar application at 30, 60, and 90 t ha-1 rates significantly increased SIC by 10, 38, and 68 t ha-1, respectively, with accumulation mainly occurring in the subsoil (below 1 m). This huge increase of SIC (mainly CaCO3) is ∼100 times larger than the inorganic carbon present in the added biochar (0.3, 0.6, or 0.9 t ha-1). The benzene polycarboxylic acid method showed that the biochar-amended soil contained more black carbon particles (6.8 times higher than control soil) in the depth of 1.4-1.6 m, which provided the direct quantitative evidence for biochar migration into subsoil after a decade. Spectral and energy spectrum analysis also showed an obvious biochar structure in the biochar-amended subsoil, accompanied by a Ca/Mg carbonate cluster, which provided further evidence for downward migration of biochar after a decade. To explain SIC accumulation in subsoil with biochar amendment, the interacting mechanisms are proposed: (1) biochar amendment significantly increases subsoil pH (0.3-0.5 units) 10 years after biochar application, thus forming a favorable pH environment in the subsoil to precipitate HCO3-; and (2) the transported biochar in subsoil can act as nuclei to precipitate SIC. Biochar amendment enhanced SIC by up to 80%; thus, the effects on carbon stocks in subsoil must be understood to inform strategies for carbon dioxide removal through biochar application. Our study provided critical knowledge on the impact of biochar application to topsoil on carbon stocks in subsoil in the long term.


Assuntos
Carbono , Solo , Solo/química , Sequestro de Carbono , Carvão Vegetal
5.
Environ Pollut ; 317: 120525, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36368551

RESUMO

Intercropping of crops with hyperaccumulators is a sustainable method to remediate contaminated soil without impeding agro-production. However, the function of engineered biochar in intercropping systems and its possible influence on cadmium (Cd) accumulation in hyperaccumulators remain unknown. A root box experiment on celery and Sedum alfredii with and without root separation was conducted in this study. Pristine and KMnO4-modified biochar (BCMn) were used to investigate the effects of different biochars on plant growth and Cd uptake in an intercropping system, as well as the influence of engineered biochar on Cd accumulation in hyperaccumulators. The results demonstrated that soil pH did not significantly vary with biochar application in the root separation treatment. However, BCMn significantly increased soil pH and thus reduced available Cd when the plant roots were not separated. Intercropping (no separation treatment) led to a 34% higher and 24% lower aboveground biomass of celery and S. alfredii, respectively, regardless of biochar addition. Compared with aboveground plant parts, plant roots exhibited more significant responses to biochar. Interestingly, intercropping may favour the phytoextraction of Cd by S. alfredii. In particular, the Cd uptake by S. alfredii roots substantially increased (118-187%), whereas that of celery roots decreased (51-71%) with BCMn addition, compared with other treatments. Moreover, after BCMn addition the accumulation of Cd in aboveground S. alfredii in the no separation treatment was 136% higher than that in the separation treatment. This was possibly related to the interaction of manganese (Mn) with Cd as well as the roots of S. alfredii. These findings provide new insights into the application of engineered biochar for phytoextraction, which is important for the efficient remediation of Cd-contaminated soils.


Assuntos
Sedum , Poluentes do Solo , Manganês , Cádmio/análise , Biodegradação Ambiental , Poluentes do Solo/análise , Solo , Verduras , Raízes de Plantas/química
6.
Environ Sci Pollut Res Int ; 30(2): 4592-4602, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35974264

RESUMO

Landfill of waste biomass not only poses a threat to environmental protection but also leads to a great waste of biomass resources. Hydrothermal carbonization (HTC) has been considered a promising method to convert the wet biomass into hydrochar, a high-value-added product with multiple application potentials. The cabbage waste, typical wet waste biomass with a huge production per year, was hydrothermally carbonized under 190 °C and 260 °C, respectively. The results indicated that the majority of nutrients from feedstock were dissolved in spent liquor during HTC, with only a few amounts retained on hydrochar. Temperature showed a more significant impact on hydrochar properties than retention time, which enables hydrochar to be potentially used as a soil conditioner. Particularly, the hydrochar produced at 190 °C could improve plant nutrition in the short term, while that produced at 260 °C may benefit in C sequestration. Moreover, the hydrochar dominated by meso/macropores (> 90%) would be conducive to the storage of plant-available water. But both BTX and VOCs may release during hydrochar application; thus, further field experiments are needed to test the environmental risks of hydrochar when applied as a soil amendment.


Assuntos
Brassica , Solo , Carbono , Temperatura , Nutrientes , Biomassa
7.
Cell Commun Signal ; 20(1): 31, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35292057

RESUMO

BACKGROUND: Resistance to androgen deprivation therapy remains a major challenge for the clinical treatment of patients with castration-resistant prostate cancer (CRPC). CYP1B1, a critical enzyme that catalyzes the conversion of estradiol to 4-Hydroxy-17ß-estradiol (4-OHE2), has been reported to promote the development and progression of hormone-related cancer, but its role in CRPC is unclear. METHODS: To explore the underlying mechanism which CYP1B1 promotes the prostate cancer stem cells (PCSCs) characteristics, bioinformatics analyses of human clinical prostate cancer (PCa) datasets were performed. CYP1B1, IL6, and estrogen receptor-α (ERα) expression levels were evaluated in PCa and CRPC tissues via immunohistochemistry. The high-performance liquid chromatography-mass spectrometry assay was carried out to examine intracellular 4-OHE2 levels. Serum-free suspension culture and flow cytometry assays were performed to evaluate PCSCs. Chromatin immunoprecipitation was used to validate that 4-OHE2 recruited ERα to the IL6 promoter. RESULTS: CYP1B1 expression was significantly increased in CRPC tissues and androgen-independent PCa cell lines. CYP1B1+ PCa cells were significantly enriched in bicalutamide-treated LNCaP cells, and CYP1B1 knockdown reduced the cell viability under bicalutamide treatment. In addition, CYP1B1 knockdown decreased the intracellular 4-OHE2 concentration, accompanied by reduced PCSC characteristics. In PCa cells, 4-OHE2 stimulated ERα transcriptional activity and upregulated the expression of IL6 and downstream genes of the IL6-STAT3 signaling. 4-OHE2 increased cell viability under bicalutamide treatment and promoted PCSC characteristics, while IL6 neutralizing antibody reversed these effects. Mechanistically, siERα and the ER antagonist ICI182780 significantly attenuated 4-OHE2-induced IL6 expression, and 4-OHE2 promoted the binding of ERα to the estrogen response element of the IL6 promoter. CONCLUSIONS: Our findings indicate that CYP1B1-catalyzed 4-OHE2 enhanced PCSC characteristics and attenuated bicalutamide sensitivity by ERα-mediated the IL6-STAT3 pathway activation. Our study further emphasizes the role of CYP1B1 in castration resistance and illustrates a novel mechanism of CRPC development. Video Abstract.


Assuntos
Citocromo P-450 CYP1B1 , Receptor alfa de Estrogênio , Interleucina-6 , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios , Androgênios , Castração , Catálise , Linhagem Celular Tumoral , Citocromo P-450 CYP1B1/metabolismo , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Humanos , Interleucina-6/metabolismo , Masculino , Células-Tronco Neoplásicas/metabolismo , Próstata/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
8.
Sci Total Environ ; 804: 150239, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34798750

RESUMO

It is common practice to apply manure onto soil as an effective way to increase soil fertility. However, the impact of different carbon sources on the transformation and fate of manure derived nitrogen (N) remains poorly understood. This study investigated the mineralization and immobilization turnover (MIT) of various manure-N fractions using sequential extractions and 15N tracing techniques combined after soil amendment with biochar, straw and mixtures thereof. Soil N was fractionated into mineral nitrogen (NH4+ and NO3-), microbial biomass nitrogen (MBN), hot water extractable organic nitrogen (HWDON), hydrochloric acid extractable organic nitrogen (HCl-N), and residual nitrogen (RN). Results showed that biochar addition increased the 15NH4+ content by 45% during the early stage. However, the high pH and labile C absence of biochar inhibited the remineralization of microbial immobilization N during the mid-to-late stage. Straw addition enhanced 15NH4+ assimilation by 10% to form HCl-15N. After that, microbial cellular structures and secondary metabolites were remineralized to meet crop N requirements. Adding carbon source mixtures with the organic fertilizer manifested the relationship between biochar and straw. The labile C content of the carbon sources rather than the C/N ratio was the critical factor regulating the N-MIT process. Overall, these findings offer new insights into the N transformation approaches using the co-application technique of organic amendments.


Assuntos
Esterco , Solo , Carvão Vegetal , Fertilizantes , Nitrogênio/análise
9.
Front Oncol ; 11: 787953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35096586

RESUMO

Treatment of patients with castration-resistant prostate cancer (CRPC) remains a major clinical challenge. We previously showed that estrogenic effects contribute to CRPC progression and are primarily caused by the increased endogenous estradiol produced via highly expressed aromatase. However, the mechanism of aromatase upregulation and its role in CRPC are poorly described. In this study, we report that HeyL is aberrantly upregulated in CRPC tissues, and its expression is positively correlated with aromatase levels. HeyL overexpression increased endogenous estradiol levels and estrogen receptor-α (ERα) transcriptional activity by upregulating CYP19A1 expression, which encodes aromatase, enhancing prostate cancer stem cell (PCSC) properties in PC3 cells. Mechanistically, HeyL bound to the CYP19A1 promoter and activated its transcription. HeyL overexpression significantly promoted bicalutamide resistance in LNCaP cells, which was reversed by the aromatase inhibitor letrozole. In PC3 cells, the HeyL-aromatase axis promoted the PCSC phenotype by upregulating autophagy-related genes, while the autophagy inhibitor chloroquine (CQ) suppressed the aromatase-induced PCSC phenotype. The activated HeyL-aromatase axis promoted PCSC autophagy via ERα-mediated estrogenic effects. Taken together, our results indicated that the HeyL-aromatase axis could increase endogenous estradiol levels and activate ERα to suppress PCSC apoptosis by promoting autophagy, which enhances the understanding of how endogenous estrogenic effects influence CRPC development.

10.
J Environ Manage ; 277: 111437, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33031998

RESUMO

The promising application modes of organic fertilizer (OF) and chemical nitrogen (N) fertilizer (CF) could be the homogeneous granulation (HG: OF and CF are distributed spatially evenly) and spatial heterogeneous granulation (SG: OF and CF are distributed separately in space), where the N transformation processes, such as the nitrous oxide (N2O) emissions, are greatly influenced by the spatial distribution of the OF and CF, particularly. Currently, there is a lack of in-depth understanding about the microbial mechanisms of the SG and HG application on N2O emissions, and the related functional guilds (ammonia oxidizers and heterotrophic denitrifiers) respond to the granular fertilizer is yet not known. In the present study, we made CF (15N-(NH4)2SO4), cow compost and maize straw (2% or 8% based on the N proportion) into granular of 1 cm in diameter, in HG and SG forms, respectively, and then applied these granules in soils for 80 days incubation. Results showed that, compared with HG treatments, the SG treatment promoted the ammonium (NH4+), nitrate (NO3-) and microbial biomass carbon (MBC) intensities, and increased the N2O emissions possibly through ammonia oxidize bacteria dependent nitrification and fungal denitrification. In addition, the high maize residues proportion in organic fertilizer significantly mitigated N2O emissions by the coupled impacts of suppressed nitrification and enhanced denitrification enzyme activity with high C input. Overall, our results suggest that spatial heterogeneous granulation of and CF may induce higher risk of N2O emissions and the higher proportion of maize residues could potentially mitigate such increased emissions.


Assuntos
Fertilizantes , Solo , Agricultura , Animais , Bovinos , Feminino , Fertilizantes/análise , Nitrificação , Nitrogênio/análise , Óxido Nitroso/análise
11.
Sci Total Environ ; 746: 141235, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768786

RESUMO

Combined application of organic fertilizer (OF) and chemical nitrogen (N) fertilizer (CF) is a common fertilization practice, providing better N supply pattern for crop growth. However, few studies focused on the effect of granulation method of these two fertilizers on N supply to soil. To validate this effect, we mixed the CF (15N-(NH4)2SO4) into cow manure powders with maize straw powder at rate of 2% or 8% (dry weight), respectively, in two forms, homogeneous granulation (HG) and spatial heterogeneous granulation (SG), and applied them to soil to investigate their difference in N transformations during an 80-day incubation. Results showed that there were more NH4+, NO3- and microbial biomass N (MBN) in the SG granules and the surrounding soil, while more dissolved organic N (DON) in the HG granules and the corresponding soil after day 30. At day 80, compared to HG, SG released less CF-N into the surrounding soil, but primed more organic N into mineral N. Structural equation model (SEM) revealed that DON was the main form of N transported from fertilizer granules to the surrounding soil, and then drove the changes of soil microbial activity, which determined the amount and dynamic of mineral N in the surrounding soil. These results indicated that, in heterogeneous granulation, the spatial separation between OF and CF slow down, but more importantly enhanced up, the microbial transformation of CF in the granules. This demonstrated that the spatial heterogeneous granulation of OF and CF could change the pattern of N release from fertilizer to soil and offer a potential way to optimize N fertilizer management strategies in the future.

12.
Bull Environ Contam Toxicol ; 105(1): 146-154, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32488396

RESUMO

Biochar was for the first time produced from Suaeda glauca. The immobilization of Pb and Cd by this biochar and pig manure biochar was examined in two types of soils by diethylene triamine pentaacetic acid (DTPA) extraction. Addition of biochars decreased DTPA extractable Pb and Cd in Fluvo-aquic soil with reduction rates being 11.3%-48.4% and 0.74%-64.9% compared with the control treatment. The pig manure biochar favored the immobilization of Pb and S. glauca biochar favored the immobilization of Cd. Biochars can effectively immobilize heavy metals in Fluvo-aquic soil. However, the addition of biochars increased extractable Pb and Cd in red soil, with pig manure biochars showing greater rates. This is ascribed to that the competition effects of ions released from biochar enhanced the moving of heavy metals from iron and manganese oxides bound form to organic matter bound form, and hence enhanced the mobility and bioavailability of heavy metals.


Assuntos
Cádmio/química , Chumbo/química , Poluentes do Solo/química , Animais , Disponibilidade Biológica , Carvão Vegetal/química , Chenopodiaceae , Compostos de Manganês , Esterco , Metais Pesados/análise , Óxidos , Solo , Poluentes do Solo/análise , Suínos
13.
Sci Total Environ ; 714: 136532, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31981863

RESUMO

The development of distinct biochar from agricultural waste for soil and environment remediation is valuable. Moderate pretreatment with sodium hydroxide may open the lignocellulosic structure of crop straw and then enhance the impregnation of iron oxides and phosphates, finally leading to the production of distinct biochars. In this study, two common agricultural wastes of rice and cotton straw were first treated with a dilute NaOH solution and then soaked in either Fe-Co nitrate or H3PO4 solution. The biochars produced through a slow pyrolysis process were then analyzed with respect to their physico-chemical and adsorptive properties. The results showed that all pretreatments remarkably changed the physico-chemical properties of the feedstocks and subsequently endowed the biochars with distinct characteristics. The biochars had specific surface areas (SSAs) ranging from 12.26 to 581.13 m2/g, total pore volumes (TPVs) ranging from 0.033 to 0.3736 cm3/g and average pore volumes (APSs) ranging from 2.57 to 10.76 nm. They also contained a large amount of positive charge, an anion exchange capacity (pH 3.5) ranging from 251.78 to 810.13 mmol/kg, and a certain amount of negative charge as well, cation exchange capacity (pH 7.0) ranging from 108.22 to 464.67 mmol/kg. The adsorption capacities of the modified biochars toward both Pb2+ and Cd2+ were 23.07-82.74% and 16.90-556.33% higher than those of pristine biochars, respectively. Of the modified biochars, the Fe-Co-composite biochar showed many promising physico-chemical and adsorptive properties for adsorbing divalent metals of both Pb2+ and Cd2+ and might thus have high potential as a soil amendment and an alternative adsorbent for environmental remediation.


Assuntos
Oryza , Adsorção , Carvão Vegetal , Fenômenos Magnéticos , Solo , Poluentes do Solo
14.
Sci Total Environ ; 708: 134829, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31806304

RESUMO

Soil aggregates play an important function in soil carbon sequestration because larger aggregates have higher soil organic carbon contents. A field experiment was set up in 2009 that included four treatments, i.e., B0, B30, B60, and B90 representing biochar application rates of 0, 30, 60, and 90 t ha-1, respectively. In 2017, we investigated the soil aggregate distribution, biochar and n-SOC contents in soil and different aggregate sizes using the ignition method, as well as the contribution of wheat and maize residues to n-SOC content in each aggregate by isotopic analysis. The results showed that, relative to B0, the n-SOC content presented an 14.0% decrease in B30, compared with an 18.8% and 8.2% increase in B60 and B90 (p < 0.05), respectively. Furthermore, the decreased n-SOC content in B30 was due to the decreased proportions of < 53 µm and 1000-250 µm aggregates. The increased n-SOC content in B60 was due to the significantly enhanced proportion of 2000-1000 µm and 1000-250 µm aggregates because the n-SOC contents of these two aggregates size classes were not changed by biochar. However, in B90, the increased n-SOC content was ascribed to the enhanced proportions of 2000-1000 µm and < 53 µm aggregates, although the n-SOC content in 2000-1000 µm aggregate was significantly decreased by biochar. Further analysis showed that the decreased n-SOC content in 2000-1000 µm aggregates was associated with decreased wheat-derived n-SOC content. In synthesis, our study showed a long-term effect of biochar on the n-SOC content by mainly changing soil aggregation and native organic carbon derived from wheat residue, and this effect was dependent on the applied amount. The biochar rate of 60 t ha-1 is recommended for carbon sequestration in terms of the more pronounced negative priming of native SOC, while the feasible combination between other biochars and soils needs further clarification.


Assuntos
Solo , Carbono , Sequestro de Carbono , Carvão Vegetal
15.
Cancer Lett ; 467: 72-84, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31499120

RESUMO

Castration-resistant prostate cancer (CRPC) following androgen deprivation therapy remains a major obstacle advanced prostate cancer management. Aromatase catalyzes estrogen from androgens, yet the role of aromatase-generated endogenous estrogen in CRPC is poorly understood. In this study, we assessed the expression and function of aromatase in CRPC. We found that aromatase expression was significantly increased in CRPC tissues and cell lines. In some prostate cancer cell lines, aromatase was predominantly expressed in CD44+ subsets. Bicalutamide treatment significantly increased aromatase expression, and CYP19A1 expression positively correlated with estrogen responses and epithelial-mesenchymal transition. Aromatase knockdown in PC3 cells reduced invasiveness and decreased metastasis-related gene expression. The aromatase inhibitor, letrozole, attenuated tumour metastasis in castrated PC3-xenograft mice. Mechanistically, aromatase-induced endogenous estrogen promoted estrogen receptor-α (ERα) binding to matrix metalloproteinase 12 (MMP12) promoter estrogen response element (ERE). MMP12 co-localized with CD44 on the cell membrane and MMP12 knockdown significantly reduced estradiol-induced PC3 invasion. Taken together, our findings indicated that increased endogenous estrogen, catalysed by elevated aromatase levels, enhanced MMP12 expression via ERα, participated in CRPC progression and promoted tumour metastasis. Thus, aromatase represents a potential novel therapeutic target for CRPC.


Assuntos
Aromatase/genética , Aromatase/metabolismo , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , Metaloproteinase 12 da Matriz/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Anilidas/administração & dosagem , Anilidas/farmacologia , Animais , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/metabolismo , Letrozol/administração & dosagem , Letrozol/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas/administração & dosagem , Nitrilas/farmacologia , Células PC-3 , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Compostos de Tosil/administração & dosagem , Compostos de Tosil/farmacologia , Regulação para Cima/efeitos dos fármacos
16.
Cell Commun Signal ; 17(1): 50, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31122254

RESUMO

BACKGROUND: Prostate cancer (PCa) is the second leading cause of mortality and a leading cause of malignant tumors in males. Prostate cancer stem cells (PCSCs) are likely the responsible cell types for cancer initiation, clinical treatment failure, tumor relapse, and metastasis. Estrogen receptor alpha (ERα) is mainly expressed in the basal layer cells of the normal prostate gland and has key roles in coordinating stem cells to control prostate organ development. Here, we investigated the roles of the estrogen-ERα signaling pathway in regulating PCSCs. METHODS: Correlation of CD49f and ERα/NOTCH1 was analyzed in human clinical datasets and tissue samples. Flow cytometry was used to sort CD49fHi and CD49fLow cells. EZH2 recruitment by ERα and facilitation of ERα binding to the NOTCH1 promoter was validated by Co-IP and ChIP. Primary tumor growth, tumor metastasis and sensitivity to 17ß-estradiol (E2) inhibitor (tamoxifen) were evaluated in castrated mice. RESULTS: ERα expression was significantly higher in CD49fHi prostate cancer basal stem-like cells (PCBSLCs), which showed basal and EMT features with susceptibility to E2 treatment. ERα-induced estrogen effects were suggested to drive the NOTCH1 signaling pathway activity via binding to the NOTCH1 promoter. Moreover, EZH2 was recruited by ERα and acted as a cofactor to assist ERα-induced estrogen effects in regulating NOTCH1 in PCa. In vivo, E2 promoted tumor formation and metastasis, which were inhibited by tamoxifen. CONCLUSIONS: Our results implicated CD49f+/ERα + prostate cancer cells associated with basal stem-like and EMT features, named EMT-PCBSLCs, in heightened potential for promoting metastasis. NOTCH1 was regulated by E2 in CD49fHi EMT-PCBSLCs. These results contribute to insights into the metastatic mechanisms of EMT-PCBSLCs in PCa.


Assuntos
Transição Epitelial-Mesenquimal , Receptor alfa de Estrogênio/metabolismo , Neoplasias da Próstata/metabolismo , Receptor Notch1/metabolismo , Animais , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Integrina alfa6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Fenótipo , Neoplasias da Próstata/patologia , Receptor Notch1/genética
17.
Ecol Evol ; 9(6): 3239-3250, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30962889

RESUMO

Different types of steppes could provide heterogeneous habitat environments for underground microorganisms, but much less is known about how soil microbes fit the distinct habitats and what are the underlying mechanisms in shaping their community patterns.We simultaneously examined the community compositions and structures of soil bacteria, fungi, and diazotrophs across desert, typical, and meadow steppes in Inner Mongolia using high-throughput sequencing.The results showed that soil bacteria, fungi, and diazotrophs exhibited different distribution patterns across steppe types. Although different steppes displayed obvious differences in climate conditions, plant traits, and soil properties, most of bacterial species were shared by all the steppes while only a few species were unique, indicating that the soil bacterial compositions were hardly influenced by the steppe types. Nevertheless, the habitat heterogeneity could cause shifts in the relative abundance of some bacterial groups, which resulted in significant changes in the community structure of soil bacteria across steppes. However, the fungal community compositions and structures were similar in typical and meadow steppes but that in desert steppe were significantly different. Whereas, the community compositions and structures of diazotrophs were strongly related to the steppe types. In this study, the similar parent material backgrounds of the steppe soils might be the important factor in shaping the homologous bacterial compositions. However, the variations in soil fertility, soil water repellency, and plant species across steppes would be the major driving forces in regulating the compositions and structures of fungal communities, while the diazotrophic communities would be more closely related to the changes in plant traits and soil fertility among steppes.Our results provided evidence of habitat specificity for different microbial groups and their underlying drivers.

18.
PLoS One ; 14(4): e0209635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30947266

RESUMO

Soils are heterogeneous and microbial spatial distribution can clearly indicate the spatial characteristics of the soil carbon and nitrogen cycle. However, it is not clear how long-term fertilization affects the spatial distribution of microbial biomass in fluvo-aquic soil. We collected fluvo-aquic soil samples (topsoil 0-7.5 cm and sub-topsoil 7.5-20 cm) using a spatially-explicit design within three 40.5 m2 plots in each of four fertilization treatments. Fertilization treatments were: cropping without fertilizer inputs (CK); chemical nitrogen, phosphorus, and potassium fertilizer (NPK); chemical fertilizer with straw return (NPKS); and chemical fertilizer with animal manure (NPKM). Variables included soil microbial biomass carbon (MBC) and nitrogen (MBN), and MBC/MBN. For both soil layers, we hypothesized that: microbial biomass was lowest in CK but with the largest spatial heterogeneity; and microbial biomass was highest in NPKM and NPKS but with the lowest spatial heterogeneity. Results showed that: (1) Fertilization significantly increased MBC and MBN more in topsoil than sub-topsoil but had no MBC/MBN changes. (2) The coefficient of variation (CV) and Cochran's C showed that variation was largest in CK in topsoil and NPK in sub-topsoil and that variation of topsoil was generally lower than in sub-topsoil. The sample size of the three variables was largest in CK in topsoil but had little variation among the other treatments. (3) The trend-surface model showed that within-plot heterogeneity varied substantially with fertilization (NPKM = NPK > NPKS > CK), but Moran's I and the interpolation map showed that spatial variability with fertilization followed the order NPK > NPKS > CK = NPKM at a fine scale in topsoil. In sub-topsoil, the trend-surface model showed that within-plot heterogeneity followed the order NPKM = CK > NPK > NPKS and that the fine-scale pattern was NPKM>NPK = NPKS>CK. MBC had the highest spatial heterogeneity among the three variables in both soil layers. Our results indicate that the application of organic fertilizer (straw or manure) reduced the variation of MBC and MBN but increased the spatial variability of MBC and MBN. The spatial variation of the three variables was MBC > MBN > MBC/MBN regardless of whether variation was considered at the plot-scale or the fine-scale in both layers.


Assuntos
Carbono/análise , Fertilizantes , Nitrogênio/análise , Microbiologia do Solo , Agricultura , Biomassa , Fertilizantes/análise , Ciclo do Nitrogênio , Fósforo/análise , Potássio/análise
19.
Sci Total Environ ; 657: 1237-1245, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30677890

RESUMO

Increased spring precipitation in semi-arid grasslands could improve annual primary productivity. However, little is known about the responses of soil microbes to individual spring precipitation. In this study, we combined phospholipid fatty acid (PLFA) and DNA-based high-throughput sequencing analyses to investigate short-term (days) shifts in the soil microbial community composition after a simulated spring precipitation. Under field conditions, the soils (approx. -0.3 MPa) were exposed to either a watering of 20 cm or natural drought, and soil samples were collected at days 1, 3, 5, 8, and 12 after watering. Soil labile organic carbon (C) and nitrogen (N) as well as microbial biomass C (MBC) were positively correlated with soil water content (SWC). Spring watering significantly increased plant phosphorus (P) uptake, but had no impact on soil available P (AP). Watering increased the PLFA biomarkers indicative for Gram-negative (G-) bacteria and fungi. Two phyla of G- bacteria, Proteobacteria and Bacteroidetes, as well as the fungal phylum Ascomycota were more abundant when SWC increased. In addition to SWC and its related environmental factors such as C and N availabilities, AP appeared to be an important factor in shaping the soil microbial community composition. The study highlights the combination use of the methods based on different microbial biomarkers (PLFA vs. DNA), and the results were in line with each other. While the PLFA-based method was more sensitive to short-term shifts in soil microbial community composition in response to a precipitation event, DNA-based method could provide more information on the microbial taxa at a finer taxonomic resolution. Our results provide methodological insights for future research on short-term response of soil microbial community to changing environmental conditions.


Assuntos
Ácidos Graxos/análise , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Microbiota/genética , Microbiologia do Solo , Bacteroides/genética , Biomassa , Carbono/análise , China , Pradaria , Nitrogênio/análise , Fosfolipídeos/análise , Plantas , Proteobactérias/genética , Chuva , Estações do Ano , Solo/química , Temperatura
20.
Prostate ; 77(14): 1424-1437, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28850686

RESUMO

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is involved in pathogenesis of human benign prostatic hyperplasia (BPH). Estrogenic signaling pathways may stimulate the induction of EMT. However, the details of estradiol (E2) and estrogen receptors (ERs) effects on EMT, as well as E2-induced modulation of benign prostatic epithelial cell phenotype in vitro have not been completely clarified. METHODS: The effects of E2 on EMT markers and cytokeratins (CKs) expression were evaluated in benign epithelial cell lines BPH-1 and RWPE-1, which were cultured both in two-dimensional (2D) culture and three-dimensional (3D) culture model using hanging drop technique or 3D Matrigel model. ER antagonist, ICI182,780, was used to confirm the regulatory effects of E2 on EMT and phenotypic modulation. In 3D culture, immunohistochemical stainings were performed to detect the specific phenotype of cells that underwent EMT in acinar-like spheroids formed by RWPE-1. To illustrate the exact function of ERs in E2-induced EMT and phenotypic modulation, specific short interfering RNAs (siRNAs), and agonists were used to knockdown or activate individual ERs, respectively. RESULTS: E2-induced EMT was observed both in 2D and 3D culture, with related regulation of EMT markers expression at both mRNA and protein level. In addition, E2 down-regulated luminal cell type markers CK18 and CK8 and up-regulated basal cell type markers CK5 and CK14. E2 also increased intermediate type markers CK15 and CK17, while it attenuated CK19 in 3D culture. ICI182,780 blocked E2-induced EMT and cell phenotypic switching. In 3D Matrigel culture, Vimentin was co-expressed with ERα and CK17, as well as with SMemb, which is related to cell status switching and proliferation. Knockdown of ERα but not GPR30 inhibited EMT, while ERß knockdown facilitated EMT process. Knockdown of ERα blocked E2-induced EMT both in RWPE-1 and BPH-1. MRNA expression of EMT markers was stimulated by ERα-specific agonist PPT and inhibited by ERß-specific agonist DPN. CONCLUSIONS: Estrogenic effect mediated by ERα can promote EMT. E2 is also an inductive factor of cell phenotypic switching. Cell type modulation is associated with E2-induced EMT in benign prostatic epithelial cells. Taken together the results support a contribution of estrogens to the pathogenesis of BPH in elderly men.


Assuntos
Transição Epitelial-Mesenquimal , Hiperplasia Prostática , Neoplasias da Próstata , Receptores de Estrogênio , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Estradiol/farmacologia , Estrogênios/farmacologia , Humanos , Masculino , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Transdução de Sinais/fisiologia
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