Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Small ; : e2310865, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678537

RESUMO

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

2.
Environ Res ; 242: 117799, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042521

RESUMO

The use of municipal solid waste incineration fly ash, commonly referred to as "fly ash", as a supplementary cementitious material (SCM), has been explored to mitigate the CO2 emissions resulting from cement production. Nevertheless, the incorporation of fly ash as an SCM in mortar has been shown to weaken its compressive strength and increase the risk of heavy metal leaching. In light of these challenges, this study aims to comprehensively evaluate the influence of CO2 pressure, temperature, and residual water/binder ratio on the CO2 uptake and compressive strength of mortar when combined with fly ash. Additionally, this study systematically examines the feasibility of mechanochemical pretreatment, which enhances the homogenization of fly ash and augments the density of the mortar's microstructure. The results indicate that the use of mechanochemical pretreatment leads to a notable 43.6% increase in 28-day compressive strength and diminishes the leaching of As, Ba, Ni, Pb, Se, and Zn by 17.9-77.8%. Finally, a reaction kinetics model is proposed to elucidate the CO2 sequestration process under varying conditions. These findings offer valuable guidance for incorporating fly ash as an SCM and CO2 sequestrator in mortar.


Assuntos
Metais Pesados , Eliminação de Resíduos , Resíduos Sólidos/análise , Cinza de Carvão , Dióxido de Carbono , Incineração , Metais Pesados/análise , Carbono , Eliminação de Resíduos/métodos , Material Particulado
3.
Angew Chem Int Ed Engl ; 59(7): 2606-2611, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31814218

RESUMO

Discrete nanosheets of silicon-doped AlPO4 molecular sieves (SAPO-34) with a thickness of ≈7 nm have been prepared through morphology-reserved synthesis with a lamellar aluminum phosphate as precursor. Cages of the nanosheets are in situ incorporated with copper oxide clusters. The CuO@SAPO-34 nanosheets exhibit a large external surface area with a high number of (010) channel pores on the surface. Due to the thin morphology, copper oxide clusters occupy the outmost cages with a probability >50 %. The distinctive configuration facilitates a new concept of pore mouth catalysis, i.e., reactant molecules larger than the pores cannot enter the interior of the molecular sieves but can interact with the CuO clusters at "the mouth" of the pore. In heterogeneous catalysis, CuO@SAPO-34 nanosheets have shown top performance in one-pot oxidation of cyclohexane to adipic acid by O2 , a key compound for the manufacture of nylon-66, which is so far produced using non-green nitric acid oxidation.

4.
Water Sci Technol ; 78(5-6): 1001-1009, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30339525

RESUMO

In this work, the novel ß-cyclodextrin modified mesostructured silica coated multi-walled carbon nanotubes (MWCNTs) composites were synthesized and applied for the removal of parabens in aqueous solution. The prepared MWCNTs/SiO2/ß-CD composites were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and thermogravimetric analysis. The effects of the amount of adsorbent, pH and elution solvents on the removal efficiency of parabens from water solutions were investigated. Under the optimized conditions, over 95% removal efficiency was achieved by using 40 mg of MWCNTs/SiO2/ß-CD adsorbents to absorb the parabens from 60 mL of 0.5 µg/mL parabens solutions. The solution pH in the range from 5 to 9 has no influence on the removal efficiency and the parabens sorption capacity of the prepared adsorbents were around 0.75 µg/mg. Furthermore, the stability and reusability studies demonstrated that the prepared MWCNTs/SiO2/ß-CD composites are cost-effective adsorbents for the removal of parabens from water with high regeneration efficiency. The composites fabricated in this study could become an attractive candidate for water purification.


Assuntos
Nanotubos de Carbono/química , Parabenos/química , Dióxido de Silício/química , Adsorção , Microscopia Eletrônica de Varredura , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , Poluentes Químicos da Água , Purificação da Água/métodos , Difração de Raios X , beta-Ciclodextrinas/química
5.
J Anal Appl Pyrolysis ; 121: 75-83, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28344372

RESUMO

The experimental results on detection and identification of intermediate radicals and molecular products from gas-phase pyrolysis of cinnamyl alcohol (CnA), the simplest non-phenolic lignin model compound, over the temperature range of 400-800 °C are reported. The low temperature matrix isolation - electron paramagnetic resonance (LTMI-EPR) experiments along with the theoretical calculations, provided evidences on the generation of the intermediate carbon and oxygen centered as well as oxygen-linked, conjugated radicals. A mechanistic analysis is performed based on density functional theory to explain formation of the major products from CnA pyrolysis; cinnamaldehyde, indene, styrene, benzaldehyde, 1-propynyl benzene, and 2-propenyl benzene. The evaluated bond dissociation patterns and unimolecular decomposition pathways involve dehydrogenation, dehydration, 1,3-sigmatropic H-migration, 1,2-hydrogen shift, C-O and C-C bond cleavage processes.

6.
Fish Physiol Biochem ; 41(2): 437-47, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25274419

RESUMO

Retinol-binding protein 4 (rbp4) is mainly synthesized in the liver, where it binds retinol and then enters the bloodstream, delivering retinol to cells. The full-length cDNA coding rbp4 was cloned from Megalobrama amblycephala. The amino acid sequence showed strong homology with the homologues of other vertebrates, and all structural and functional domains were highly conserved. The mRNA levels in different tissues and development stages detected by quantitative real-time PCR revealed that M. amblycephala rbp4 was highly expressed in liver (P < 0.001), but the lower levels were also detected in eyes, kidney, intestine, and spleen. During the different development stages, the rbp4 mRNA appeared until 28 hours post-fertilization (hpf), underwent a slight drop, and then gradually increased after 50 hpf. In addition, the promoter sequence of M. amblycephala rbp4 was obtained using thermal asymmetric interlaced PCR. Two single nucleotide polymorphism sites (-385A>G and -329C>T) were found in the promoter. Transfection with recombinant plasmids of two different haplotypes (GT, AC) showed that 9-cis-retinoic acid (RA) increased the promoter activity, but the AC haplotype was more sensitive to RA.


Assuntos
Cyprinidae/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Ligação ao Retinol/genética , Proteínas de Ligação ao Retinol/metabolismo , Tretinoína/farmacologia , Alitretinoína , Animais , Sequência de Bases , Cyprinidae/metabolismo , Haplótipos/genética , Fígado/metabolismo , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Análise de Sequência de DNA/veterinária
7.
Fish Shellfish Immunol ; 38(1): 88-95, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24582889

RESUMO

A novel CC chemokine gene, chemokine CC motif ligand 4 (CCL4), was isolated from Megalobrama amblycephala. The full-length cDNA was 913 bp, encoding 94 amino acid residues. The deduced amino acid sequence possessed the typical arrangement of four cysteines as found in other known CC chemokines. The expression of M. amblycephala CCL4 during the early development showed the mRNA levels before hatching and at 62 h post fertilized (hpf) were significantly higher than other post-hatching stages (P < 0.05). Besides, it was widely expressed in all detected tissues with the highest transcription in liver, followed by intestine, spleen and gill, where a larger number of immune cells including lymphocytes and macrophages are present. Our findings had fully confirmed that CCL4 expression was strongly induced in vitro and quickly up-regulated after nitrite stress, then substantially altered in all tested tissues, supporting a potential pro-inflammatory function. We also indicated that inflammation effect might firstly happen in blood after nitrite stress. Furthermore, the tissue expression differences of CCL4 among three natural populations revealed that CCL4 mRNA in Yuni Lake population was obviously higher than the other two populations, Liangzi Lake population and Poyang Lake population, which will provide valuable insights into breeding strategies for selecting population with better immune property of M. amblycephala.


Assuntos
Quimiocina CCL4/metabolismo , Cyprinidae/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Nitritos/farmacologia , Sequência de Aminoácidos , Animais , Quimiocina CCL4/genética , China , Clonagem Molecular , Demografia , Lagos , Dados de Sequência Molecular , Filogenia
8.
J Comput Biol ; 31(2): 128-146, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38227389

RESUMO

The effective reproduction number (Rt) is one of the most important epidemiological parameters, providing suggestions for monitoring the development trend of diseases and also for adjusting the prevention and control policies. However, a few studies have focused on the performance of some common computational methods for Rt. The purpose of this article is to compare the performance of three computational methods for Rt: the time-dependent (TD) method, the new time-varying (NT) method, and the sequential Bayesian (SB) method. Four evaluation methods-accuracy, correlation coefficient, similarity based on trend, and dynamic time warping distance-were used to compare the effectiveness of three computational methods for Rt under different time lags and time windows. The results showed that the NT method was a better choice for real-time monitoring and analysis of the epidemic in the middle and late stages of the infectious disease. The TD method could reflect the change of the number of cases stably and accurately, and was more suitable for monitoring the change of Rt during the whole process of the epidemic outbreak. When the data were relatively stable, the SB method could also provide a reliable estimate for Rt, while the error would increase when the fluctuation in the number of cases increased. The results would provide suggestions for selecting appropriate Rt estimation methods and making policy adjustments more timely and effectively according to the change of Rt.


Assuntos
COVID-19 , Humanos , Número Básico de Reprodução , Teorema de Bayes
9.
J Mater Chem B ; 12(13): 3240-3248, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38437473

RESUMO

Proteolysis targeting chimeras (PROTACs) is a promising strategy for cancer therapy. However, the always-on bioactivity of PROTACs may lead to non-target toxicity, which restricts their antitumor performance. Here, we developed an X-ray radiation responsive PROTAC nanomicelle (RCNprotac) by covalently conjugating a reported small molecule PROTAC (MZ1) to hydrophilic PEG via a diselenide bond-containing carbon chain, which then self-assembled into a 141.80 ± 5.66 nm nanomicelle. The RCNprotac displayed no bioactivity during circulation due to the occupation of the hydroxyl group on the E3 ubiquitin ligand component and could effectively accumulate at the tumor site owing to the enhanced permeability and retention effect. Upon exposure to X-ray radiation, the radiation-sensitive diselenide bonds were broken to specifically release MZ1 for tumor BRD4 protein degradation. Furthermore, the reduction in the BRD4 protein level could increase the tumor's sensitivity to radiation. RCNprotac showed a synergistic enhancement of antitumor effects both in vitro and in vivo. We believe that this X-ray-responsive PROTAC nanomicelle could provide a new strategy for the X-ray-activated spatiotemporally controlled protein degradation and for the BRD4 proteolysis enhanced tumor radiosensitivity.


Assuntos
Nanopartículas , Neoplasias , Humanos , Proteólise , Proteínas Nucleares/metabolismo , Fatores de Transcrição , Neoplasias/patologia , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/metabolismo
10.
Sci Total Environ ; 912: 169482, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38135065

RESUMO

The process of urbanization has resulted in a continuous growth of the production of municipal solid waste, consequently leading to the increase of municipal solid waste incineration fly ash (MSWI FA) over time. This has prompted the need for effective disposal and value-added utilization strategies for MSWI FA. In this study, a hydrothermal method was employed to synthesize CaAl layered double hydroxides (LDHs) using MSWI FA as the raw material. The main objective was to investigate how different synthesis parameters affect the crystallinity of the layered bimetallic hydroxides. Subsequently, the synthesized LDHs were characterized using various techniques such as BET, SEM, XRD, FT-IR, and XPS. The results revealed the presence of calcium and aluminum cations in the interlayer region of the synthesized material, with chloride ions, sulfate ions, and acetate ions being the predominant anions. Moreover, the formation of LDHs presents an effective approach for the self-purification of leachates derived from MSWI FA. The LDHs exhibited excellent adsorption capacity for Cd2+ and Cu2+ in wastewater, with maximum values of 730 mg·g-1 and 446 mg·g-1, respectively. The adsorption mechanisms involved isomorphous substitution, complexation, as well as the precipitation of hydroxides or interlayer anions. This method presents a novel approach for effectively utilizing MSWI FA to produce environmentally friendly value-added adsorbents.

11.
Hortic Res ; 11(6): uhae120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38919559

RESUMO

Understanding the intricate regulatory mechanisms underlying the anthocyanin content (AC) in fruits and vegetables is crucial for advanced biotechnological customization. In this study, we generated high-quality haplotype-resolved genome assemblies for two mulberry cultivars: the high-AC 'Zhongsang5801' (ZS5801) and the low-AC 'Zhenzhubai' (ZZB). Additionally, we conducted a comprehensive analysis of genes associated with AC production. Through genome-wide association studies (GWAS) on 112 mulberry fruits, we identified MaVHAG3, which encodes a vacuolar-type H+-ATPase G3 subunit, as a key gene linked to purple pigmentation. To gain deeper insights into the genetic and molecular processes underlying high AC, we compared the genomes of ZS5801 and ZZB, along with fruit transcriptome data across five developmental stages, and quantified the accumulation of metabolic substances. Compared to ZZB, ZS5801 exhibited significantly more differentially expressed genes (DEGs) related to anthocyanin metabolism and higher levels of anthocyanins and flavonoids. Comparative analyses revealed expansions and contractions in the flavonol synthase (FLS) and dihydroflavonol 4-reductase (DFR) genes, resulting in altered carbon flow. Co-expression analysis demonstrated that ZS5801 displayed more significant alterations in genes involved in late-stage AC regulation compared to ZZB, particularly during the phase stage. In summary, our findings provide valuable insights into the regulation of mulberry fruit AC, offering genetic resources to enhance cultivars with higher AC traits.

12.
Bioact Mater ; 39: 206-223, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38827172

RESUMO

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

13.
Theranostics ; 14(1): 116-132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164154

RESUMO

Background: Therapeutic interventions such as synthetic drugs and microRNA (miR) modulators have created opportunities for mitigating hepatic ischemia/reperfusion injury (HIRI) by alleviating mitochondrial dysfunction. However, delivering multi-therapeutic ingredients with low toxicity to hepatocytes still lags behind its development. Methods: In this study, we endowed exosomes with delivery function to concentrate on hepatocytes for multidimensionally halting mitochondria dysfunction during HIRI. Concretely, exosomes were reprogrammed with a transmembrane protein CD47, which acted as a "camouflage cloak" to mimic the "don't eat me" mechanism to escape from immune surveillance. Besides, HuR was engineered bridging to the membrane by fusing with CD47 and located in the cytoplasm for miR loading. Results: This strategy successfully delivered dual payloads to hepatocytes and efficiently protected mitochondria by inhibiting the opening of mitochondrial permeability transition pore (mPTP) and upregulating mitochondrial transcription factor A (TFAM), respectively. Conclusions: The reprogramming of exosomes with CD47 and HuR for targeted delivery of CsA and miR inhibitors represents a promising therapeutic strategy for addressing HIRI. This approach shows potential for safe and effective clinical applications in the treatment of HIRI.


Assuntos
Exossomos , MicroRNAs , Traumatismo por Reperfusão , Humanos , Antígeno CD47/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Exossomos/metabolismo , Traumatismo por Reperfusão/metabolismo , Mitocôndrias/metabolismo , MicroRNAs/metabolismo
14.
Sci Total Environ ; 872: 162133, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36773918

RESUMO

This paper investigates the impact of in-situ release and sequestration of CO2 on the compressive strength, volume of permeable voids, phase change, hydration reaction, and micro-morphology of cement mortars. Two Linde Type A (LTA) zeolites with micro-pore dimensions of 5 Å and 4 Å (i.e., LTA 5A and 4A zeolites) were employed as CO2 carriers herein. The incorporation of 312 wt% plain LTA 5A and 4A zeolites increases the 1-day compressive strength of the mortars. However, the use of plain LTA 5A zeolite shows marginal contributions to the 7 and 28-day compressive strengths of the mortars, whilst using plain LTA 4A zeolite even deteriorates their 7 and 28-day compressive strengths. The micro-structural analyses reveal that the addition of LTA zeolites promotes the cement hydration and improves the mean chain length (MCL) of calcium aluminosilicate hydrates (C-A-S-H). Nevertheless, this introduces numerous weak points or even a porous structure to the cement matrix. In contrast, in-situ release of CO2 via LTA zeolites significantly enhances the compressive strengths of the mortars at various ages, as this can further facilitate the hydration evolution and improve the MCL of C-A-S-H. Moreover, in-situ release of CO2 brings an incremental content of calcium carbonates. The calcium carbonate contents in the specimens containing 12 wt% LTA 5A and 4A zeolites are increased by 5.3 wt% and 4.8 wt%, respectively. This leads to homogenous distributions of calcite with a grain size of 150600 nm. Thus, LTA 5A zeolite outperforms LTA 4A zeolite with regard to CO2 uptake and the corresponding mechanical properties. This work presents in initial exploration into the application of porous pozzolanic materials in conjunction of CO2 in cement-based materials.

15.
Environ Sci Technol ; 46(9): 5025-31, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22458922

RESUMO

Phytoextraction has become one of the most promising remediation techniques for heavy metal (HM) contaminated soils. However, the technique invariably produces large amounts of HM-enriched hyperaccumulators, which need further safe disposal. In this study, two different thermal treatment methods are investigated as potential options for evaporative separation of HMs from the residues. A horizontal tube furnace and a vertical entrained flow tube furnace were used for testing the disposal of grounded hyperaccumulators. The release characteristics of HMs (Cd, Cu, Pb, and Zn) into flue gas and residues were investigated for thermal treatment of the Cd and Zn hyperaccumulators Sedum plumbizincicola and Sedum alfredii. In a horizontal tube furnace, incineration favors the volatilization of Cu and Cd in contrast to pyrolysis. The percentages of HMs in residues after incineration are lower than those after pyrolysis, especially for Cd, Pb, and Zn. However, in an entrained flow tube furnace, Zn content in flue gas increases with increasing temperature, but Cu and Cd contents are fluctuated. In addition, a higher incineration temperature enhances the Cu content in residues.


Assuntos
Gases/análise , Incineração , Metais Pesados/análise , Sedum/metabolismo , Biodegradação Ambiental , Temperatura Alta , Metais Pesados/metabolismo
16.
Front Psychol ; 13: 1104618, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36817390

RESUMO

In this study, we demonstrate that high short-term gains on the A-share market may lead to significant losses in the future and potentially cause a market catastrophe. To study the accumulation, outbreak, and cross-sector spillover process of systemic risk in the Chinese stock market, we define right-tail risk as a large rally process that may lead to left-tail losses in the future and construct a tail volatility spillover network by distinguishing between left-tail and right-tail risk. In the risk accumulation process, the market expectation bias of common shocks considerably magnifies heterogeneity risk, and in the risk outbreak and spillover processes, the greatest systemically important and systemically susceptible sectors are banking and information technology, respectively. In addition, the level of risk spillover is extremely sensitive to tail shocks and increases as tail shocks intensify. Moreover, right-tail risk has more forward-looking predictive power for left-tail risk. Apart from achieving immediate regulatory objectives, Chinese authorities must consider market expectation bias when implementing rules. Additionally, authorities want to be wary of right-tail risk, which has the potential to create serious and pervasive damage in the future if the market is allowed to be unregulated during short-term spikes.

17.
Chemosphere ; 293: 133464, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34974043

RESUMO

Organic dyes, a type of high toxic and carcinogenic chemicals that present severe threats to human and aquatic life, are the most commonly seen organic pollutants in wastewater of industries such as textile, rubber, cosmetic industry etc. Various techniques for the removal of dyes are compared in this review. Adsorption has proven to be a facile and promising approach for the removal of dyes in wastewater. This work focuses on the latest development of various porous materials for the adsorption of organic dyes. The characteristics, functionalization and modification of different porous materials are also presented. Furthermore, adsorption behaviors and mechanism of these adsorbents in the adsorption of organic dyes are critically reviewed. Finally, challenges and opportunities for future research in the development of novel materials for the highly efficient removal of dyes are proposed.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Corantes , Humanos , Porosidade , Águas Residuárias , Poluentes Químicos da Água/análise
18.
Cells ; 11(7)2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35406631

RESUMO

Non-alcoholic fatty liver disease (NAFLD) held a high global prevalence in recent decades. Hepatic lipid deposition is the major characteristic of NAFLD. We aim to explore the mechanisms of psoralen on lipid deposition in NAFLD. The effects of psoralen on insulin resistance, lipid deposition, the expression and membrane translocation of glucose transporter type 4 (GLUT4), autophagy, and lipogenesis enzymes were determined on sodium oleate-induced L02 cells. Chloroquine and 3-MA were employed. The AMP-activated protein kinase alpha (AMPKα) was knocked down by siRNA. Psoralen alleviated insulin resistance in sodium oleate-induced L02 hepatocytes by upregulating the expression and membrane translocation of GLUT4. Psoralen inhibited lipid accumulation by decreasing the expression of key lipogenesis enzymes. Psoralen promotes autophagy and the autophagic flux to enhance lipolysis. Psoralen promoted the fusion of the autophagosome with the lysosome. Both chloroquine and 3-MA blocked the effects of psoralen on autophagy and lipid accumulation. The AMPKα deficiency attenuated the effects of psoralen on autophagy and lipid accumulation. Our study demonstrated that as an antioxidant, psoralen attenuates NAFLD by alleviating insulin resistance and promoting autophagy via AMPK, suggesting psoralen to be a promising candidate for NAFLD.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Cloroquina/farmacologia , Ficusina/farmacologia , Humanos , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico/farmacologia
19.
Thorac Cancer ; 13(2): 190-201, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34825483

RESUMO

BACKGROUND: Docetaxel (DTX) exhibits antitumor effects against breast cancer by stabilizing microtubules and increasing the accumulation of reactive oxygen species (ROS). DTX extravasation during infusion often causes skin injury. The present study aimed to investigate the effects and mechanisms of icaritin (ICT) on DTX-induced skin injury. METHODS: The effects of ICT on the viability and apoptosis of HaCaT cells were measured by SRB assay and flow cytometry, respectively. Endogenous LC3 puncta and microtubules were determined by immunofluorescence. The number of mitochondria was measured by MitoTracker orange staining. ROS were determined by dihydroethidium staining. The expression of markers of ROS and autophagy were measured by western blotting. Chloroquine, compound D, and tamoxifen were employed as the inhibitor for autophagy and AMPK, estrogen receptors (ERs) modulator, respectively. RESULTS: DTX inhibited the viability and decreased apoptosis of HaCaT cells, which can be rescued by ICT. ICT decreased microtubule bundles, increased the number of mitochondria, and attenuated ROS of HaCaT cells induced by DTX. ICT blocks autophagy and the autophagic flux. Compound C or tamoxifen diminished the protection effects of ICT on DTX-treated HaCaT cells. CONCLUSION: ICT alleviates DTX-induced skin injury by suppressing ROS, reducing microtubule bundles, and blocking autophagy via ERs. Our study indicated that ICT may be a potential candidate for DTX-induced skin injury.


Assuntos
Docetaxel/efeitos adversos , Flavonoides/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/metabolismo , Dermatopatias/induzido quimicamente , Dermatopatias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células HaCaT , Humanos
20.
J Clin Transl Hepatol ; 9(3): 373-383, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34221923

RESUMO

BACKGROUND AND AIMS: Lipid accumulation is the major characteristic of non-alcoholic fatty liver disease, the prevalence of which continues to rise. We aimed to investigate the effects and mechanisms of icaritin on lipid accumulation. METHODS: Cells were treated with icaritin at 0.7, 2.2, 6.7, or 20 µM for 24 h. The effects on lipid accumulation in L02 and Huh-7 cells were detected by Bodipy and oil red O staining, respectively. Mitochondria biogenesis of L02 cells was detected by MitoTracker Orange staining. Glucose uptake and adenosine triphosphate content of 3T3-L1 adipocytes and C2C12 myotubes were detected. The expression levels of proteins in the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway, biomarkers of autophagy, and mitochondria biogenesis were measured by western blotting. LC3 puncta were detected by immunofluorescence. RESULTS: Icaritin significantly attenuated lipid accumulation in L02 and Huh-7 cells and boosted the mitochondria biogenesis of L02 cells. Icaritin enhanced glucose uptake, decreased adenosine triphosphate content, and activated the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes. Icaritin boosted autophagy and also enhanced the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts. However, icaritin decreased autophagy and promoted mitochondria biogenesis in 3T3-L1 adipocytes and C2C12 myotubes. CONCLUSIONS: Icaritin attenuates lipid accumulation by increasing energy expenditure and regulating autophagy by activating the AMPK pathway.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA