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1.
Development ; 147(11)2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527935

RESUMO

Here, we report novel tumour suppressor activity for the Drosophila Argonaute family RNA-binding protein AGO1, a component of the miRNA-dependent RNA-induced silencing complex (RISC). The mechanism for growth inhibition does not, however, involve canonical roles as part of the RISC; rather, AGO1 controls cell and tissue growth by functioning as a direct transcriptional repressor of the master regulator of growth, Myc. AGO1 depletion in wing imaginal discs drives a significant increase in ribosome biogenesis, nucleolar expansion and cell growth in a manner dependent on Myc abundance. Moreover, increased Myc promoter activity and elevated Myc mRNA in AGO1-depleted animals requires RNA polymerase II transcription. Further support for transcriptional AGO1 functions is provided by physical interaction with the RNA polymerase II transcriptional machinery (chromatin remodelling factors and Mediator Complex), punctate nuclear localisation in euchromatic regions and overlap with Polycomb Group transcriptional silencing loci. Moreover, significant AGO1 enrichment is observed on the Myc promoter and AGO1 interacts with the Myc transcriptional activator Psi. Together, our data show that Drosophila AGO1 functions outside of the RISC to repress Myc transcription and inhibit developmental cell and tissue growth.This article has an associated 'The people behind the papers' interview.


Assuntos
Proteínas Argonautas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Fatores de Transcrição/metabolismo , Animais , Animais Geneticamente Modificados/metabolismo , Proteínas Argonautas/antagonistas & inibidores , Proteínas Argonautas/genética , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Larva/metabolismo , MicroRNAs/metabolismo , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , Interferência de RNA , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ribossomos/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Transcrição Gênica , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/fisiologia
2.
Appl Microbiol Biotechnol ; 107(15): 4961-4971, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37306709

RESUMO

Paper mulberry (Broussonetia papyrifera), as a new woody forage with high-protein characteristic, is being widely used in ruminant feeding. However, little is known about the comprehensive microbiota picture of whole ruminal niches (liquid, solid, and epithelium) under paper mulberry diet. To gain a better understanding of feeding paper mulberry on the rumen microbiota, the effects of fresh paper mulberry, paper mulberry silage, or a conventional high-protein alfalfa silage on rumen fermentation products and microbiota in rumen niches of Hu lambs were studied. Forty-five Hu lambs were randomly divided into 3 treatments with 15 replicates in each treatment. No significant difference was observed among treatments in the average daily gain (ADG). The fresh paper mulberry treatment had lower (P < 0.05) pH and higher (P < 0.05) total volatile fatty acids (TVFA) compared with silage treatments, but the fermentation parameters did not show significant differences between paper mulberry silage and alfalfa silage treatments. The Shannon index did not show a significant difference (P < 0.05) among treatments except between fresh paper mulberry and alfalfa silage treatment in rumen epithelial niches. Butyrivibrio and Treponema were the predominant genera in the rumen epithelial fraction, while Prevotella and Rikenellaceae_RC9 dominated in both rumen liquid and solid fractions. These results indicated the paper mulberry supplement did not have distinct impact on the microbial diversity and growth performance compared with alfalfa silage, especially for paper mulberry silage, which might help us develop an alternative animal feeding strategy of replacing alfalfa with paper mulberry. KEY POINTS: • Feeding paper mulberry silage did not show significant impact on the growth performance compared with alfalfa silage treatment. • Feeding fresh paper mulberry reduced rumen pH value and increased total volatile fatty acid. • The microbial diversity did not show significant difference among treatments.


Assuntos
Broussonetia , Microbiota , Morus , Feminino , Animais , Ovinos , Leite , Lactação , Rúmen/metabolismo , Dieta/veterinária , Silagem , Ração Animal/análise , Ácidos Graxos Voláteis/metabolismo , Fermentação , Medicago sativa
3.
Angew Chem Int Ed Engl ; 62(13): e202218670, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36723229

RESUMO

Photochemical afterglow systems have drawn considerable attention in recent years due to their regulable photophysical properties and charming application potential. However, conventional photochemical afterglow suffered from its unrepeatability due to the consumption of energy cache units as afterglow photons are emitted. Here we report a novel strategy to realize repeatable photochemical afterglow (RPA) through the reversible storage of 1 O2 by 2-pyridones. Near-infrared afterglow with a lifetime over 10 s is achieved, and its initial intensity shows no significant reduction over 50 excitation cycles. A detailed mechanism study was conducted and confirmed the RPA is realized through the singlet oxygen-sensitized fluorescence emission. Furthermore, the generality of this strategy is demonstrated and tunable afterglow lifetimes and colors are achieved by rational design. The developed RPA is further applied for attacker-misleading information encryption, presenting a repeatable-readout.

4.
Angew Chem Int Ed Engl ; 62(45): e202312239, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37728507

RESUMO

Pyridine oximes produced from aldehyde or ketone with hydroxylamine (NH2 OH) have been widely applied in pharmaceutics, enzymatic and sterilization. However, the important raw material NH2 OH exhibits corrosive and unstable properties, leading to substantial energy consumption during storage and transportation. Herein, this work presents a novel method for directly synthesizing highly valuable pyridine oximes using in situ generated NH2 OH from electrocatalytic NO reduction with well-design nanofiber membranes (Al-NFM) derived from NH2 -MIL-53(Al). Particularly, 2-pyridinealdoxime, the precursor of antidote pralidoxime (2-PAM) for nerve agents suffering from scarcity and high cost, was achieved with a Faraday efficiency up to 49.8 % and a yield of 92.1 %, attributing to the high selectivity of NH2 OH production on Al-NFM, further easily reacted with iodomethane to produce 2-PAM. This study proposes a creative approach, having wide universality for synthesizing pyridine and other oximes with a range of functional groups, which not only facilitates the conversion of exhaust gas (NO) and waste water (NO2 - ) into valuable chemicals especially NH2 OH production and in situ utilization through electrochemistry, but also holds significant potential for synthesis of neuro detoxifying drugs to humanity security.

5.
Acta Pharmacol Sin ; 43(11): 2917-2928, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35508720

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is emerging as an epidemic risk factor for hepatocellular carcinoma (HCC). The progression of NAFLD to HCC is closely associated with paracrine communication among hepatic cells. Vascular endothelial growth factor A (VEGFA) plays a key role in NAFLD and HCC; however, the cellular communication of VEGFA in the pathological transition from NAFLD to HCC remains unclear. Here, we found that VEGFA elevation was considerably distributed in hepatocytes of clinical and murine NAFLD-HCC specimens. Notably, progression from NAFLD to HCC was attenuated in hepatocyte-specific deletion of Vegfa (VegfaΔhep) mice. Mechanistically, VEGFA activated human hepatic stellate cell (HSC) LX2 into a fibrogenic phenotype via VEGF-VEGFR signaling in fatty acid medium, and HSC activation was largely attenuated in VegfaΔhep mice during NAFLD-HCC progression. Additionally, a positive correlation between VEGFA and hepatic fibrosis was observed in the NAFLD-HCC cohort, but not in the HBV-HCC cohort. Moreover, LX2 cells could be activated by conditioned medium from NAFLD-derived organoids, but not from HBV livers, whereas this activation was blocked by a VEGFA antibody. In summary, our findings reveal that hepatocyte-derived VEGFA contributes to NAFLD-HCC development by activating HSCs and highlight the potential of precisely targeting hepatocytic VEGFA as a promising therapeutic strategy for NAFLD-HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Células Estreladas do Fígado , Fator A de Crescimento do Endotélio Vascular/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Neoplasias Hepáticas/patologia , Hepatócitos/metabolismo , Fígado/metabolismo , Cirrose Hepática/patologia , Progressão da Doença
6.
Mikrochim Acta ; 189(12): 454, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36416956

RESUMO

A sensitive electrochemical sensor for the determination of carbendazim (CBZ) was developed with Ni-doping nanoporous carbon-graphene composite (G-Ni/C) as the electrode material. The combination of graphene and Ni-doping nanoporous carbon not only prevented the aggregation of graphene, but also improved electric conductivity and substantially enhanced the electro catalytic activity for CBZ sensing. The electrochemical characterization of G-Ni/C towards CBZ determination was conducted by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) . The sensor based on G-Ni/C/GCE exhibits good electroanalytical activity towards the electro-oxidation of CBZ at the potential of + 0.6 V vs Ag/AgCl. Some key factors including sample pH, scan rates, accumulation potential, and accumulation time were investigated. The method offered a wide linear range of 0.04 to 10.0 µM with a detection limit of 8.9 nM. The obtained sensor was successfully employed for the determination of CBZ in pond water and juice samples with RSD < 5.7% and recoveries in the range 91.3-111%. In the present work, Ni-doping nanoporous carbon-graphene composite (G-Ni/C) was prepared by directly pyrolysis of GO/Ni-MOF. The electrochemical sensor based on G-Ni/C /GCE was applied for sensitive determination of carbendazim (CBZ) in pond water, peach, and lemon juices samples.


Assuntos
Grafite , Grafite/química , Carbono/química , Técnicas Eletroquímicas/métodos , Porosidade , Água
7.
J Clin Lab Anal ; 35(1): e23513, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32761657

RESUMO

BACKGROUND: Although DNA of high quality can be easily prepared from cultured cells with commercially available kits, many studies involve a large number of samples which increases the cost drastically. We optimized two simple and inexpensive methods for preparing DNA suitable for digital PCR from a small number of cells directly from wells of 96-well plates. METHODS: Cells (number: 103 -104 ) were lysed with a Direct PCR® lysis buffer or a 10% Chelex100® solution. The lysates were further purified and concentrated by means of DNA precipitation with a blue-colored glycogen as a carrier. PCR and digital PCR were used to evaluate the efficiency of the two methods. RESULTS: For 1000 cells from one primary culture and two tumor cell lines, DNA was reproducible and obtained with recovery rate (obtained/expected amount of DNA) in the range of 50%-90% as measured by the fluorometer dyes instrument Qubit. Using 8 out of a total of 10 µL DNA solution for 1000 cells, both conventional PCR and digital PCR were successful. For digital PCR, more than 1600 positive droplets were obtained for DNA from 1000 cells using the Direct PCR® method, corresponding to a yield efficiency of approximately 80%. Further reducing the number of cells down to 100 would be possible with 160 positive droplets expected. Both reagents are inexpensive (0.08€/sample). CONCLUSIONS: Two methods are efficient, especially the Direct PCR® reagent-based method provides a simple and inexpensive method for preparing DNA suitable for digital PCR from small number of cells.


Assuntos
DNA/isolamento & purificação , Reação em Cadeia da Polimerase , Linhagem Celular Tumoral , Células Cultivadas , DNA/análise , DNA/genética , Humanos , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas
8.
J Transl Med ; 18(1): 195, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398139

RESUMO

BACKGROUND: Green tea drinking has been proven to lower lipid and exert cardiovascular protection, while the potential mechanism has not been fully determined. This study was to investigate whether the beneficial impact of epigallocatechingallate (EGCG), a type of catechin in green tea on lipids is associated with proprotein convertase subtilisin/kexin type 9 (PCSK9) pathways. METHODS: We studied the effects and underlying molecular mechanism of EGCG or green tea on regulating cholesterol from human, animal and in vitro. RESULTS: In the age- and gender-matched case control observation, we found that individuals with frequent tea consumption (n = 224) had the lower plasma PCSK9 and low density lipoprotein cholesterol (LDL-C) levels compared with ones without tea consumption (n = 224, p < 0.05). In the high fat diet (HFD) fed rats, EGCG administration significantly lowered circulating PCSK9 concentration and liver PCSK9 expression, along with up-regulated LDL receptor (LDLR) expression but decreased level of LDL-C. In hepatic cell study, similar results were obtained regarding the impact of EGCG on LDLR and PCSK9 expression. The assay transposase-accessible chromatic with high-throughput sequencing (ATAC-seq) and subsequent results suggested that two transcription factors, hepatocyte nuclear factor-1α (HNF-1α) and forkhead box class O (FoxO) 3a involved in inhibitory action of EGCG on PCSK9 expression. CONCLUSIONS: The present study demonstrates that EGCG suppresses PCSK9 production by promoting nuclear FoxO3a, and reducing nuclear HNF1α, resulting in up-regulated LDLR expression and LDL uptake in hepatocytes. Thereby inhibiting liver and circulating PCSK9 levels, and ultimately lowering LDL-C levels.


Assuntos
Catequina , Proteína Forkhead Box O3 , Fator 1-alfa Nuclear de Hepatócito , Pró-Proteína Convertase 9 , Receptores de LDL , Animais , Catequina/farmacologia , LDL-Colesterol , Proteína Forkhead Box O3/antagonistas & inibidores , Proteína Forkhead Box O3/metabolismo , Humanos , Ratos
9.
Int J Mol Sci ; 21(22)2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202662

RESUMO

Ultraviolet (UV) light and non-thermal plasma (NTP) are promising chair-side surface treatment methods to overcome the time-dependent aging of dental implant surfaces. After showing the efficiency of UV light and NTP treatment in restoring the biological activity of titanium and zirconia surfaces in vitro, the objective of this study was to define appropriate processing times for clinical use. Titanium and zirconia disks were treated by UV light and non-thermal oxygen plasma with increasing duration. Non-treated disks were set as controls. Murine osteoblast-like cells (MC3T3-E1) were seeded onto the treated or non-treated disks. After 2 and 24 h of incubation, the viability of cells on surfaces was assessed using an MTS assay. mRNA expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were assessed using real-time reverse transcription polymerase chain reaction analysis. Cellular morphology and attachment were observed using confocal microscopy. The viability of MC3T3-E1 was significantly increased in 12 min UV-light treated and 1 min oxygen NTP treated groups. VEGF relative expression reached the highest levels on 12 min UV-light and 1 min NTP treated surfaces of both disks. The highest levels of HGF relative expression were reached on 12 min UV light treated zirconia surfaces. However, cells on 12 and 16 min UV-light and NTP treated surfaces of both materials had a more widely spread cytoskeleton compared to control groups. Twelve min UV-light and one min non-thermal oxygen plasma treatment on titanium and zirconia may be the favored times in terms of increasing the viability, mRNA expression of growth factors and cellular attachment in MC3T3-E1 cells.


Assuntos
Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Osteoblastos/metabolismo , Oxigênio/farmacologia , Gases em Plasma/farmacologia , RNA Mensageiro/sangue , Titânio/química , Raios Ultravioleta , Zircônio/química , Animais , Adesão Celular/efeitos dos fármacos , Adesão Celular/efeitos da radiação , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Camundongos , Osteoblastos/citologia , Propriedades de Superfície
10.
Int J Mol Sci ; 20(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717459

RESUMO

A number of modifications have been developed in order to enhance surface cytocompatibility for prosthetic support of dental implants. Among them, ultraviolet (UV) light and non-thermal plasma (NTP) treatment are promising methods. The objective of this study was to compare the effects of UV light and NTP on machined titanium, zirconia and modified polyetheretherketone (PEEK, BioHPP) surfaces in vitro. Machined samples of titanium, zirconia and BioHPP were treated by UV light and NTP of argon or oxygen for 12 min each. Non-treated disks were set as controls. A mouse fibroblast and a human gingival fibroblast cell line were used for in vitro experiments. After 2, 24 and 48 h of incubation, the attachment, viability and cytotoxicity of cells on surfaces were assessed. Results: Titanium, zirconia and BioHPP surfaces treated by UV light and oxygen plasma were more favorable to the early attachment of soft-tissue cells than non-treated surfaces, and the number of cells on those treated surfaces was significantly increased after 2, 24 and 48 h of incubation (p < 0.05). However, the effects of argon plasma treatment on the cytocompatibility of soft tissue cells varied with the type of cells and the treated material. UV light and oxygen plasma treatments may improve the attachment of fibroblast cells on machined titanium, zirconia and PEEK surfaces, that are materials for prosthetic support of dental implants.


Assuntos
Cetonas/farmacologia , Gases em Plasma/farmacologia , Polietilenoglicóis/farmacologia , Titânio/farmacologia , Raios Ultravioleta , Zircônio/farmacologia , Animais , Benzofenonas , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Humanos , Cetonas/toxicidade , Camundongos Endogâmicos C57BL , Polietilenoglicóis/toxicidade , Polímeros , Propriedades de Superfície , Titânio/toxicidade , Zircônio/toxicidade
11.
Nucleic Acids Res ; 44(16): 7646-58, 2016 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-27207882

RESUMO

Despite two decades of research, the major function of FBP-family KH domain proteins during animal development remains controversial. The literature is divided between RNA processing and transcriptional functions for these single stranded nucleic acid binding proteins. Using Drosophila, where the three mammalian FBP proteins (FBP1-3) are represented by one ortholog, Psi, we demonstrate the primary developmental role is control of cell and tissue growth. Co-IP-mass spectrometry positioned Psi in an interactome predominantly comprised of RNA Polymerase II (RNA Pol II) transcriptional machinery and we demonstrate Psi is a potent transcriptional activator. The most striking interaction was between Psi and the transcriptional mediator (MED) complex, a known sensor of signaling inputs. Moreover, genetic manipulation of MED activity modified Psi-dependent growth, which suggests Psi interacts with MED to integrate developmental growth signals. Our data suggest the key target of the Psi/MED network in controlling developmentally regulated tissue growth is the transcription factor MYC. As FBP1 has been implicated in controlling expression of the MYC oncogene, we predict interaction between MED and FBP1 might also have implications for cancer initiation and progression.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Complexo Mediador/metabolismo , Morfogênese , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Proteínas Nucleares , Regiões Promotoras Genéticas/genética , Ligação Proteica , Subunidades Proteicas/metabolismo , RNA Polimerase II/metabolismo , Proteínas de Ligação a RNA , Transcrição Gênica
12.
BMC Oral Health ; 18(1): 63, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29636044

RESUMO

BACKGROUND: Iron disorder and abnormal expression of hepcidin play important roles in many diseases, but it is still unclear in chronic periodontitis (CP) and type 2 diabetes mellitus (T2DM). We aimed to assess ferritin and hepcidin levels in serum and saliva of CP patients with or without T2DM. METHODS: Serum and unstimulated whole saliva samples were collected from 88 participants, who were categorized into 4 groups based on the presence or absence of CP or T2DM. Demographics and general health parameters were recorded. Full-mouth clinical periodontal parameters including probing pocket depth, clinical attachment loss, bleeding index, and plaque index were recorded. Chemiluminescence microparticle immunoassay and enzyme-linked immunosorbent assay were used to detect ferritin and hepcidin concentrations, respectively, in serum and saliva. RESULTS: Serum ferritin and hepcidin levels in the CP and CP with T2DM groups were higher than in the control group (P < 0.05). Serum hepcidin and serum ferritin are linear correlated (P < 0.001). Serum hepcidin/ferritin values in the CP with T2DM group were significantly lower than those in the T2DM and control groups. Moreover, salivary ferritin levels in the CP and T2DM groups were higher than those in the control group (P < 0.05). There was positively correlation between salivary ferritin and serum ferritin (P = 0.017). Hepcidin concentrations were relatively low in saliva. CONCLUSIONS: These results suggest that iron overload and hepcidin inadequacy existed in CP with T2DM patients. Salivary ferritin might provide a reference for body iron load. TRIAL REGISTRATION: ChiCTR-ROC-17012780.


Assuntos
Periodontite Crônica/sangue , Diabetes Mellitus Tipo 2/sangue , Ferritinas/sangue , Hepcidinas/sangue , Saliva/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Periodontite Crônica/complicações , Índice de Placa Dentária , Diabetes Mellitus Tipo 2/complicações , Feminino , Ferritinas/análise , Hepcidinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/sangue , Índice Periodontal
13.
J Hepatol ; 65(2): 314-24, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27154061

RESUMO

BACKGROUND & AIMS: Considerable evidence suggests that adrenergic signaling played an essential role in tumor progression. However, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms remain unknown. METHODS: The effect of adrenaline in hepatocarcinogenesis was observed in a classical diethylnitrosamine-induced HCC mouse model. Effects of ADRB2 signaling inhibition in HCC cell lines were analyzed in proliferation, apoptosis, colony formation assays. Autophagy regulation by ADRB2 was assessed in immunoblotting, immunofluorescence and immunoprecipitation assays. In vivo tumorigenic properties and anticancer effects of sorafenib were examined in nude mice. Expression levels of ADRB2 and hypoxia-inducible factor-1α (HIF1α) in 150 human HCC samples were evaluated by immunohistochemistry. RESULTS: We uncovered that adrenaline promoted DEN-induced hepatocarcinogenesis, which was reversed by the ADRB2 antagonist ICI118,551. ADRB2 signaling also played an essential role in sustaining HCC cell proliferation and survival. Notably, ADRB2 signaling negatively regulated autophagy by disrupting Beclin1/VPS34/Atg14 complex in an Akt-dependent manner, leading to HIF1α stabilization, reprogramming of HCC cells glucose metabolism, and the acquisition of resistance to sorafenib. Conversely, inhibition of ADRB2 signaling by ICI118,551, or knockdown ADRB2 expression, led to enhanced autophagy, HIF1α destabilization, tumor growth suppression, and improved anti-tumor activity of sorafenib. Consistently, ADRB2 expression correlated positively with HIF1α in HCC specimens and was associated with HCC outcomes. CONCLUSIONS: Our results uncover an important role of ADRB2 signaling in regulating HCC progression. Given the efficacy of ADRB2 modulation on HCC inhibition and sorafenib resistance, adrenoceptor antagonist appears to be a putative novel treatment for HCC and chemoresistance. LAY SUMMARY: ADRB2 signaling played an essential role in sustaining hepatocellular carcinoma cell proliferation and survival. ADRB2 signaling negatively regulated autophagy, leading to hypoxia-inducible factor-1α stabilization, reprogramming of hepatocellular carcinoma cells glucose metabolism, and the acquisition of resistance to sorafenib. Adrenoceptor antagonist appears to be a putative novel treatment for hepatocellular carcinoma and chemoresistance.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Autofagia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Camundongos , Camundongos Nus , Niacinamida/análogos & derivados , Compostos de Fenilureia , Receptores Adrenérgicos beta 2 , Transdução de Sinais , Sorafenibe
14.
Gut ; 64(1): 156-67, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24572141

RESUMO

OBJECTIVE: Liver tumour-initiating cells (T-ICs) are critical for hepatocarcinogenesis. However, the underlying mechanism regulating the function of liver T-ICs remains unclear. METHODS: Tissue microarrays containing 242 hepatocellular carcinoma (HCC) samples were used for prognostic analysis. Magnetically activated cell sorting was used to isolate epithelial cell adhesion molecule (EPCAM)-positive cells. The gene expressions affected by miR-429 were determined by arrays. Co-immunoprecipitation was used to study interactions among retinoblastoma protein (RB1), Rb binding protein 4 (RBBP4) and E2F transcription factor 1 (E2F1). The DNA methylation status in CpG islands was detected by quantitative methylation analysis. miRNAs in microvesicles were isolated by a syringe filter system. RESULTS: The significant prognosis factor miR-429 was upregulated in HCC tissues and also in primary liver T-ICs isolated from clinical samples. The enrichment of miR-429 in EPCAM+ T-ICs contributed to hepatocyte self-renewal, malignant proliferation, chemoresistance and tumorigenicity. A novel functional axis involving miR-429, RBBP4, E2F1 and POU class 5 homeobox 1 (POU5F1 or OCT4) governing the regulation of liver EPCAM+ T-ICs was established in vitro and in vivo. The molecular mechanism regulating miR-429 expression, involving four abnormal hypomethylated sites upstream of the miR-200b/miR-200a/miR-429 cluster, was first defined in both EPCAM+ liver T-ICs and very early-stage HCC tissues. miR-429 secreted by high-expressing cells has the potential to become a proactive signalling molecule to mediate intercellular communication. CONCLUSIONS: Epigenetic modification of miR-429 can manipulate liver T-ICs by targeting the RBBP4/E2F1/OCT4 axis. This miRNA might be targeted to inactivate T-ICs, thus providing a novel strategy for HCC prevention and treatment.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Epigênese Genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Células-Tronco Neoplásicas , Proteína do Retinoblastoma/fisiologia , Humanos , Prognóstico , Células Tumorais Cultivadas
15.
Lung Cancer ; 194: 107889, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39029358

RESUMO

OBJECTIVES: To investigate the variability and diagnostic efficacy of respiratory-gated (RG) PET/CT based radiomics features compared to ungated (UG) PET/CT in the differentiation of non-small cell lung cancer (NSCLC) and benign lesions. METHODS: 117 patients with suspected lung lesions from March 2020 to May 2021 and consent to undergo UG PET/CT and chest RG PET/CT (including phase-based quiescent period gating, pQPG and phase-matched 4D PET/CT, 4DRG) were prospectively included. 377 radiomics features were extracted from PET images of each scan. Paired t test was used to compare UG and RG features for inter-scan variability analysis. We developed three radiomics models with UG and RG features (i.e. UGModel, pQPGModel and 4DRGModel). ROC curves were used to compare diagnostic efficiencies, and the model-level comparison of diagnostic value was performed by five-fold cross-validation. A P value < 0.05 was considered as statistically significant. RESULTS: A total of 111 patients (average age ± standard deviation was 59.1 ± 11.6 y, range, 29 - 88 y, and 63 were males) with 209 lung lesions were analyzed for features variability and the subgroup of 126 non-metastasis lesions in 91 patients without treatment before PET/CT were included for diagnosis analysis. 101/377 (26.8 %) 4DRG features and 82/377 (21.8 %) pQPG features showed significant difference compared to UG features (both P<0.05). 61/377 (16.2 %) and 59/377 (15.6 %) of them showed significantly better discriminant ability (ΔAUC% (i.e. (AUCRG - AUCUG) / AUCUG×100 %) > 0 and P<0.05) in malignant recognition, respectively. For the model-level comparison, 4DRGModel achieved the highest diagnostic efficacy (sen 73.2 %, spe 87.3 %) compared with UGModel (sen 57.7 %, spe 76.4 %) and pQPGModel (sen 63.4 %, spe 81.8 %). CONCLUSION: RG PET/CT performs better in the quantitative assessment of metabolic heterogeneity for lung lesions and the subsequent diagnosis in patients with NSCLC compared with UG PET/CT.

16.
Anim Nutr ; 18: 1-16, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38989011

RESUMO

The effects of Lactobacillus plantarum in microencapsulation (LPM) on intestinal development in layer chicks were investigated in this study, as well as the colonization of L. plantarum in the gut. A total of 480 healthy Hy-Line Brown layer chicks at 0 d old were randomly divided into 4 groups (8 replicates each treatment), and the diets of these birds were supplemented with nothing (control), L. plantarum (0.02 g/kg feed; 109 CFU/kg feed), LPM (1.0 g/kg feed; 109 CFU/kg feed) and wall material of LPM (WM; 0.98 g/kg feed), respectively. Compared to control, LPM improved growth performance and intestinal development of layer chicks, evidenced by significantly increased body weight, average daily gain, average daily feed intake, villus height, villus height/crypt depth, as well as weight and length of the duodenum, jejunum and ileum (P < 0.05). These results could be attributed to the increased colonization of L. plantarum in the gut, which was verified by significant increases in lactic acid content, viable counts in chyme and mucosa (P < 0.05), as well as a visible rise in number of strains labeled with fluorescein isothiocyanate. Meanwhile, the relative abundances of Lactobacillus and Bifidobacterium significantly increased in response to microencapsulated L. plantarum supplementation (P < 0.05), accompanied by the significant up-regulation of colonization related genes (P < 0.05), encoding solute carrier family, monocarboxylate transporter, activin A receptor, succinate receptor and secretogranin II. To sum up, microencapsulated L. plantarum supplementation promoted intestinal development, which could be attributed to the enhancement of L. plantarum colonization in the intestine through the mutual assistance of Bifidobacterium and interactions with colonization related transmembrane proteins.

17.
Phys Chem Chem Phys ; 15(34): 14295-302, 2013 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-23872744

RESUMO

A series of GdF3:Yb(3+), Ln(3+) (Ln = Ho, Tm, Er, Pr, Tb) nanoparticles were prepared by a simple and green hydrothermal method without any additives, which exhibited an ellipse-like shape with a diameter of 63 nm and a length of 101 nm on average. To prove the existence (or not) of near infrared quantum cutting for various lanthanide ion couples (Yb/Ho; Yb/Tm; Yb/Er; Yb/Pr; Yb/Tb) in one host lattice (GdF3), the measured luminescence spectra and decay lifetimes of these samples were analysed. Furthermore, the band structures and densities of state of GdF3 were also studied with the help of first-principles calculations, and the direct band gap of GdF3 was estimated to be 7.443 eV wide. Based on this, detailed processes and possible mechanisms of the luminescence phenomena are discussed. GdF3:Yb(3+), Ln(3+) nanoparticles may have potential applications in modifying the solar spectrum to enhance the efficiency of silicon solar cells.

18.
Food Chem ; 427: 136674, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37385066

RESUMO

Wide use of phenylurea herbicide has caused serious residue problem and threaten human health. It is important to develop viable method for their sensitive determination. Herein, a multi-functionalized porous polymer was prepared by crosslinking hexafluorobisphenol A with pyromellitic dianhydride. Using the multi-functionalized porous polymer as solid phase extraction sorbent, combined with high performance liquid chromatography, a sensitive method was established for determining phenylurea herbicides in beverages and celtuces. High sensitivity was achieved, with method detection limit (S/N = 3) of 0.01---0.025 ng mL-1 for beverages, 1.70 ng g-1 for celtuce, and quantitation limits of 0.03---0.10 ng mL-1 for beverages, 5.00 ng g-1 for celtuce. The method recoveries were 80.5---120.0 % with relative standard deviations lower than 6.1%. Adsorption mechanism mainly involved F-π, F-O, π-π, polar interactions and hydrogen-bonding interactions. This study offers a simple protocol to develop multi-functional sorbents for extraction of organic pollutants.


Assuntos
Herbicidas , Polímeros , Humanos , Polímeros/química , Herbicidas/análise , Porosidade , Bebidas/análise , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Adsorção , Limite de Detecção
19.
Int J Oral Implantol (Berl) ; 16(3): 197-208, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37767615

RESUMO

PURPOSE: To determine the histological effects of ultraviolet light and cold atmospheric plasma treatment on the osseointegration of titanium implants in vivo. MATERIALS AND METHODS: Six juvenile pigs were divided into three groups of two animals each. A total of 54 titanium implants were placed randomly in the pigs' calvarial bone (nine implants per pig). Of these, 18 implants served as untreated controls. The remaining 36 implants served as the experimental group and were treated with either ultraviolet light or argon plasma for 12 minutes each prior to insertion. Two pigs in each group were kept until 2, 4 and 8 weeks and then sacrificed. Resonance frequency analysis was conducted after implant placement and at the time of sacrifice. Osseointegration was evaluated using microcomputed tomography scans and histomorphometrical analysis. RESULTS: After initial loss, all implants showed a constant increase in implant stability quotient values over time without significant differences between the groups. The bone-implant contact values increased steadily for all implants over 8 weeks of healing. Surface-treated implants showed significantly higher bone-implant contact values compared to untreated implants at each time point. Bone area fraction occupancy values were almost always higher following both treatment methods; however, differences were only significant after 4 and 8 weeks for the cold atmospheric plasma group and after 4 weeks for the ultraviolet light group. CONCLUSIONS: Ultraviolet light and cold atmospheric plasma may improve histomorphometrical osseointegration of titanium implants significantly.


Assuntos
Implantes Dentários , Gases em Plasma , Suínos , Animais , Osseointegração , Titânio , Gases em Plasma/farmacologia , Raios Ultravioleta , Microtomografia por Raio-X , Propriedades de Superfície
20.
Talanta ; 258: 124441, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36958099

RESUMO

As being widely used insecticides, neonicotinoid residues are toxic and harmful to human health and aquatic ecosystems. Thus, the sensitive monitoring of neonicotinoids in water and food samples is highly desirable to reduce their risks to humans. Herein, four novel hydroxyl-functionalized nanoporous organic frameworks (OH-NOP1, OH-NOP2, OH-NOP3 and OH-NOP4) with tunable hydrophilic-hydrophobic surface have been designed and fabricated for the first time by employing luteolin as monomer and 4,4'-bis(chloromethyl)-1,1'-biphenyl as crosslinker at the molar ratio of 3:1, 1:1, 1:3 and 1:6, respectively. When the molar ratio of luteolin to crosslinker was 1:3, OH-NOP3 was obtained and it presented the highest affinity with excellent adsorption performance towards the studied neonicotinoids. The adsorption mechanism was proposed to be the strong hydrogen bond, polar interaction, Lewis acid-base interaction and pore adsorption between OH-NOP3 and neonicotinoids. Then, utilizing OH-NOP3 as sorbent for solid phase extraction cartridges, an effective method for extraction and preconcentration of neonicotinoids followed by high performance liquid chromatography analysis has been developed for quantitative detection of neonicotinoids from water and edible fungi. The method provided good linearity over the range of 0.06-100.0 ng mL-1 for lake water, 1.5-100.0 ng g-1 for pleurotus eryngii and sea-shroom. Low detection limit (at the signal to noise ratio of 3) was achieved in the range of 0.02-0.08 ng mL-1 for water, 0.50-0.60 ng g-1 for pleurotus eryngii and 0.50-0.80 ng g-1 for sea-shroom, while the limit of quantification was 0.06-0.25 ng mL-1, 1.50-1.80 ng g-1 and 1.50-2.50 ng g-1, respectively. Satisfactory method recoveries (85.1-112%) were obtained, with relative standard deviations below 8.2%. This study offered a new strategy for designing efficient sorbents to adsorb or remove organic pollutants based on the structure and properties of substrates.

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