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1.
J Hazard Mater ; 421: 126728, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34339990

RESUMO

The increasing release of nanomaterials has attracted significant concerns for human and environmental health. Similarly, the dissemination of antimicrobial resistance (AMR) is a global health crisis affecting approximately 700,000 people a year. However, a knowledge gap persists between the spread of AMR and nanomaterials. This study aims to fill this gap by investigating whether and how nanomaterials could directly facilitate the dissemination of AMR through horizontal gene transfer. Our results show that commonly-used nanoparticles (NPs) (Ag, CuO and ZnO NPs) and their ion forms (Ag+, Cu2+ and Zn2+) at realistic concentrations within aquatic environments can significantly promote the transformation of extracellular antibiotic resistance genes in Acinetobacter baylyi ADP1 by a factor of 11.0-folds, which is comparable to the effects of antibiotics. The enhanced transformation by Ag NPs/Ag+ and CuO NPs/Cu2+ was primarily associated with the overproduction of reactive oxygen species and cell membrane damage. ZnO NPs/Zn2+ might increase the natural transformation rate by stimulating the stress response and ATP synthesis. All tested NPs/ions resulted in upregulating the competence and SOS response-associated genes. These findings highlight a new concern that nanomaterials can speed up the spread of AMR, which should not be ignored when assessing the holistic risk of nanomaterials.


Assuntos
Resistência Microbiana a Medicamentos , Íons , Nanopartículas Metálicas , Acinetobacter/genética , Antibacterianos , Resistência Microbiana a Medicamentos/genética , Humanos , Íons/toxicidade , Nanopartículas Metálicas/toxicidade
2.
Chemosphere ; 287(Pt 4): 132398, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34597647

RESUMO

Antibiotic-resistant bacteria (ARB) pose a substantial threat to public health worldwide. Electrochemistry, as a low energy consumption and environmentally friendly technique, is ideal for inactivating ARB. This study explored the utility of electrochemical disinfection (ED) for inactivating ARB (Escherichia coli K-12 LE392 resistant to kanamycin, tetracycline, and ampicillin) and the regrowth potential of the treated ARB. The results revealed that 5.12-log ARB removal was achieved within 30 min of applying molybdenum carbide as the anode and cathode material under a voltage of 2.0 V. No ARB regrowth was observed in the cathode chamber after 60 min of incubation in unselective broth, demonstrating that the process in the cathode chamber was more effective for permanent inactivation of ARB. The mechanisms underlying the ARB inactivation were verified based on intercellular reactive oxygen species (ROS) measurement, membrane integrity detection, and genetic damage assessment. Higher ROS production and membrane permeability were observed in the cathode and anode groups (p < 0.001) compared to the control group (0 V). In addition, the DNA was more likely to be damaged during the ED process. Collectively, our results demonstrate that ED is a promising technology for disinfecting water to prevent the spread of ARB.


Assuntos
Desinfecção , Escherichia coli K12 , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/farmacologia , Bactérias , Eletrodos , Escherichia coli , Molibdênio , Águas Residuárias
3.
Sci Total Environ ; 804: 150180, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34517319

RESUMO

It is meaningful to study how China can maintain the sustainable utilization of natural resources and the continuous improvement of environmental conditions while ensuring the stable development of the economy and society. In this study, a new indices system was proposed for the analysis of nexus among social-economic-natural resource-environment complex systems following the DPSIR (Driving Force - Pressure - State - Impact - Respond) framework, CCD (Coupling Coordination Degree) analysis and VAR (Vector Auto-Regressive) model were applied for quantifying the synergy and trade-off of China in the nexus framework. Results showed that: (1) Although China's rapid development has caused big consumption of natural resources and increasing pollutants discharges during 1978-2018, China has not got into trouble of extreme resource depletion and ecosystem collapse. On the contrary, China guaranteed food supply, stopped forest degradation, and avoided pollution-induced healthy crises & life-shortening. (2) Adjustment of water pollution industries and the increase of wastewater treatment investment contributed 39% and 37% to the reduction of water pollutant discharge, respectively. The contribution of energy structure adjustment to acid rain control was 26%. The pollutants discharged in no less than 70% of the provinces are strictly controlled below the environmental capacity. The increase of fertilizer application and effective irrigated area contributed 32% to China's grain increase, and China's grain self-sufficiency rate has been maintained above 110%. The improvement of the water-saving irrigation rate contributed 28% to the reduction of water consumption. The reduction of comprehensive efficiency contributed 23.8% to the decrease in energy consumptions per GDP. The CCD assessment showed that China has entered a phase of pre-eminently coordinated development since 2013.


Assuntos
Ecossistema , Mudança Social , China , Conservação dos Recursos Naturais , Poluição Ambiental , Recursos Naturais , Poluição da Água
4.
Chemosphere ; 287(Pt 2): 132198, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34517238

RESUMO

97% of residential buildings are installed with secondary water supply system (SWSS) in China. In order to meet the water pressure demand, the SWSS has become a key solution to store and transport drinking water. The water age of the SWSS directly determines the quality of tap water, while total chlorine is a key indicator to evaluate the quality and safety of the water supply network. This study revealed the relationship between total chlorine and water age controlled by adjusting the liquid level of the secondary water supply tank. Models governing water age and the total chlorine concentration were developed based on the variation of the liquid level and the attenuation rate of the total chlorine in the SWSS. Furthermore, the validation was performed through case studies. The developed models can gain effective insights for determining the longest water age while guaranteeing the concentration of total chlorine meets the demand of the lower standard in SWSS. The secondary chlorine dosage would be quantified and added to the pipe network. The integration of the SWSS would be guided by water age in some old communities. The taste of tap water for direct drinking water could be improved by adjusting of water age using this model. The optimization method is easy to use for identifying efficient solutions for SWSS operation.


Assuntos
Água Potável , Purificação da Água , China , Cloro/análise , Água , Abastecimento de Água
5.
Food Chem ; 372: 131287, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34656911

RESUMO

A convenient fluorescence sensor of tetracycline (TC) was constructed based on carbon dots (CDs) and polyvinyl alcohol (PVA) hydrogel film. The immobilization of CDs in PVA carrier can stabilize the fluorescence of CDs by inhibiting the fluorescence quench due to the aggregation of CDs with time. CDs were prepared by a hydrothermal method. CDs showed bright blue fluorescence with the quantum yield of 0.35. The fluorescence of CDs was quenched by TC owing to the inner filter effect. The linear range for TC detection was 0-350 µM and the limit of detection was 0.17 µM. To test conveniently, PVA film was employed to upload CDs. Therefore, a novel sensor for TC was constructed in a visual mode. By comparison with the most of previous works, the present method displayed higher sensitivity and better selectivity. The results suggest that the present sensor has potential applications in the real-time detection of TC in food analysis.


Assuntos
Carbono , Pontos Quânticos , Corantes Fluorescentes , Polímeros , Espectrometria de Fluorescência , Tetraciclina
6.
J Phys Chem Lett ; 12(44): 10880-10885, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34730355

RESUMO

Despite the fact that chemotherapy has been widely used in the clinical treatment of breast cancer, the toxicity of chemotherapeutics to normal tissues cannot be ignored due to the low specificity. Therefore, due to the non-negligible toxicity of chemotherapeutic agents to normal tissues, tumor microenvironment (TME)-responsive cancer therapy has attracted a great deal of attention. Here, we report a TME-responsive theranostic nanoagent MnOx@PAA@HKUST-1-DSF@BSA fabricated via a layer-by-layer synthesis method. Once endocytosed by tumor cells, the nanoagent can be degraded into Mn2+ for magnetic resonance imaging and Cu2+ for Fenton-like reaction and chelating with released disulfiram in situ, achieving enhanced chemotherapy. Both in vitro and in vivo experiments demonstrate that the TME-targeted nanoagent can efficiently kill tumor cells. This work provides an alternative option for effective imaging and treatment of breast cancer without collateral damage to normal tissues.

7.
Nanoscale ; 13(43): 18349-18355, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34729576

RESUMO

Because of its limited light field mode and high Q value, the whispering-gallery-mode (WGM) cavity has been widely studied. In this study, we propose a simple, rapid, low-cost and no-manufacturing technology method that we call the drip-coating method to obtain an irregular cavity with arbitrary boundaries. By using polyvinyl alcohol (PVA) solution doped with rhodamine 6G, the irregular cavity with arbitrary boundaries was drip-coated on a high-reflection mirror, forming a WGM laser. The sample was pumped with a 532 nm pulsed laser, and the single-mode WGM and multi-WGM lasing were obtained. All WGMs are the vertical oscillation modes, which originate from both the total internal reflection of the PVA/air interface and vertical reflection of the PVA/mirror interface. The other boundaries of the cavity were not involved in the reflection and could have any shape. The mechanism of producing single-mode lasing is due to the action of the loss-gain cavity. Multi-WGM lasing is attributed to at least two groups of different WGMs existing in an irregular cavity. This can be confirmed by using a microsphere model and intensity correlation method. These results may provide an alternative for the design of WGM lasers.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34734656

RESUMO

Alpha-synuclein (α-Syn) localizes at presynaptic terminal and modulates synaptic functions. Increasing evidence demonstrate that α-Syn oligomers, forming at the early of aggregation, are cytotoxic and is thus related to brain neurodegenerative diseases. Herein, we find that vitamin D (VD) can reduce neurocytotoxicity. The reduced neurocytotoxicity might be attributed to the less amount of large-sized α-Syn oligomers inhibited by VD, measured by electrochemical collision at single particle level, which are not observable with traditionally ensembled method. Single-cell amperometry (SCA) results show that VD can recover the amount of neurotransmitter release during exocytosis induced by α-Syn oligomers, further verifying the neuroprotection of VD. Our study reveals the neuroprotective role of VD through inhibiting α-Syn aggregation, which is envisioned to be of great importance in treatment and prevention of the neurodegenerative diseases.

9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(11): 1396-1402, 2021 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-34779164

RESUMO

In 2020, the American Association of Hip and Knee Surgeons (AAHKS), the American Society of Regional Anesthesia and Pain Medicine (ASRA), the American Academy of Orthopaedic Surgeons (AAOS), the American Hip Society (THS), the American Knee Society (TKS) have worked together to develop clinical practice guidelines on the use of Opioids in primary total joint arthroplasty (TJA). This clinical practice guideline formulates recommendations for common and important questions related to the efficacy and safety of Opioids in primary TJA. This article interprets the guideline to help doctors make clinical decisions.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Cirurgiões Ortopédicos , Analgésicos Opioides , Humanos , Articulação do Joelho , Estados Unidos
10.
Front Cardiovasc Med ; 8: 731958, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796209

RESUMO

Atherosclerosis is a complex disease closely related to the function of endothelial cells (ECs), monocytes/macrophages, and vascular smooth muscle cells (VSMCs). Despite a good understanding of the pathogenesis of atherosclerosis, the underlying molecular mechanisms are still only poorly understood. Therefore, atherosclerosis continues to be an important clinical issue worthy of further research. Recent evidence has shown that long non-coding RNAs (lncRNAs) and RNA-binding proteins (RBPs) can serve as important regulators of cellular function in atherosclerosis. Besides, several studies have shown that lncRNAs are partly dependent on the specific interaction with RBPs to exert their function. This review summarizes the important contributions of lncRNAs and RBPs in atherosclerosis and provides novel and comprehensible interaction models of lncRNAs and RBPs.

11.
Sci Rep ; 11(1): 22542, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799608

RESUMO

Study on the form partitioning and content of heavy metals in soil particles with different sizes is crucial for preventing and controlling heavy metals pollution, but few studies regard soil contaminated by heavy metals as a homogeneous body. In this study (Fig. 1), goat manure, lime and phosphate were used to stabilize exogenous lead (Pb). These soil passivators' differential effects on total Pb and Pb with different chemical forms in soil particles of different sizes as well as Pb immobilization in soil were investigated. By passivation experiment in laboratory for 45 days, the passivation effect of the single and combined application treatments on exogenous Pb and partitioning characteristics were analyzed and compared. The characterization method of fine sand microstructure and mineral composition analysis was used. The results showed that the single application of P5 and combined application of LP5 had optimum passivation efficiency. The content of DTPA-Pb was reduced with P5 by 65.27% and the percentage of available Pb decreased significantly in soil particles of the four sizes. The content of TCLP-Pb and available Pb (weak acid extraction and reducible Pb) significantly decreased by 71.60 and 25.12% respectively after the application of LP5 in the original soil. Furthermore, most of the total Pb was enriched in coarse sand and clay, while its content was lower in fine sand and silt. The combined application treatment of GL5 significantly increased the content of weak acid extractable and reducible Pb in fine sand, silty sand and clay. Through SEM and XRD analysis, it was found that the diffraction peak of P5 treatment groups might be related to the formation of insoluble Pb that contained compounds, which were mainly mineral components, including quartz, feldspar and mica, and LP showed a big potential in the study on passivation of heavy metal Pb-contaminated soil in the natural environment. In conclusion, further studies on the different dosage and metal-contamination levels as well as different combination forms of passivators should be considered under natural conditions, the selection of suitable passivators according to soil texture is of great significance for remediation of Pb-contaminated soil.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34824005

RESUMO

In this paper, a nanosecond pulsed spark discharge in CO2/CH4 mixture gas at atmospheric pressure is studied with optical emission spectroscopy. A high-voltage pulse is applied across two plate-shaped electrodes at a repetition frequency of 1 kHz. Emphatically, plasma parameters of this discharge are estimated by spectroscopic methods for giving an insight into the underlying dry reforming reaction mechanism. The time-averaged optical emission is mainly caused by atomic spectral lines of excited O, H, and C+, and C2 swan bands. The vibrational temperature of 8500 ± 50 K and rotational temperature of 3200 ± 100 K are estimated by the excited C2 molecules, respectively. The electron density is calculated by Stark broadening of O (844.6 nm), Hα (656.3 nm), and Hß (486.1 nm) for 3.4 âˆ¼ 7.71 × 1017 cm-3 while C+ (723.6 nm) for 4.37 × 1018 cm-3 with an electron excitation temperature of 0.58 eV that is estimated by the intensity ratio of Hα and Hß. The determination of plasma parameters offers essential data for subsequent reaction kinetics research of the plasma-assisted dry reforming of CH4.

13.
Front Plant Sci ; 12: 726797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804083

RESUMO

Rose plants are one of the most important horticultural crops, whose commercial value mainly depends on long-distance transportation, and wounding and ethylene are the main factors leading to their quality decline and accelerated senescence in the process. However, underlying molecular mechanisms of crosstalk between wounding and ethylene in the regulation of flower senescence remain poorly understood. In relation to this, transcriptome analysis was performed on rose flowers subjected to various treatments, including control, wounding, ethylene, and wounding- and ethylene- (EW) dual treatment. A large number of differentially expressed genes (DEGs) were identified, ranging from 2,442 between the ethylene- and control-treated groups to 4,055 between the EW- and control-treated groups. Using weighted gene co-expression network analysis (WGCNA), we identified a hub gene RhWRKY33 (rchiobhmchr5g0071811), accumulated in the nucleus, where it may function as a transcription factor. Moreover, quantitative reverse transcription PCR (RT-qPCR) results showed that the expression of RhWRKY33 was higher in the wounding-, ethylene, and EW-treated petals than in the control-treated petals. We also functionally characterized the RhWRKY33 gene through virus-induced gene silencing (VIGS). The silencing of RhWRKY33 significantly delayed the senescence process in the different treatments (control, wounding, ethylene, and EW). Meanwhile, we found that the effect of RhWRKY33-silenced petals under ethylene and EW dual-treatment were stronger than those under wounding treatment in delaying the petal senescence process, implying that RhWRKY33 is closely involved with ethylene and wounding mediated petal senescence. Overall, the results indicate that RhWRKY33 positively regulates the onset of floral senescence mediated by both ethylene and wounding signaling, but relies heavily on ethylene signaling.

14.
Nanoscale ; 13(45): 18955-18960, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34779477

RESUMO

Single-element phosphorus has received extensive attention in recent years because of its remarkable photocatalytic properties. In the present experiment, amorphous red phosphorus was controllably transformed into [P12(4)]P2[and Hittorf's phosphorus structures by performing bismuth catalysis. The temperature-controllable chemical vapor transport reaction realized the conversion of more than 90% of amorphous red phosphorus to single-phase crystalline red phosphorus. Under very mild ultrasonic treatment, the high-quality [P12(4)]P2[microbelts and Hittorf's phosphorus microrods were stripped into a few layers of nanobelts and sheet-like structures, respectively. As non-metallic catalysts, their rapid photocatalytic degradations of pollutants (methyl orange) and high hydrogen evolution rates revealed the rapid charge transfer and application potential of the crystalline red phosphorus catalyst. The results of this work could provide new ideas for the development of phosphorus-based crystalline photocatalytic systems.

15.
J Interv Med ; 4(1): 49-52, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34805948

RESUMO

Objectives: To present a case series of modified transjugular intrahepatic portosystemic shunts (TIPS) and percutaneous transhepatic intrahepatic portosystemic shunts (PTIPS) in cirrhotic patients with variceal bleeding (VB). In addition, the scientific literature pertaining to PTIPS was reviewed. Methods: This retrospective clinical case series included six cirrhotic patients with VB who were treated with PTIPS after the failure of endoscopic band ligation or endoscopic injection sclerotherapy combined with vasoactive drugs. The treatment was conducted between January 2017 and June 2019 at a single institution. Three patients suffered from severe atrophy of the right or left lobar of the liver as well as the main right or left branch of the portal vein. The remaining three patients showed severe atrophy of the whole liver and portal vein, resulting in widening of the liver fissure. A paired t-test was used to compare the changes in portal pressure gradient between before and after the PTIPS operation. The rebleeding rate, treatment efficacy, complications, and technical success rate were all assessed during follow-up. Results: All six PTIPS procedures were performed successfully, with no severe procedural-related complications observed. None of the patients experienced VB during a mean follow-up of 22.8 (range, 18.0-28.0) months. The mean portosystemic pressure gradient decreased from 28.3 â€‹± â€‹4.3 â€‹mmHg pre-procedure to 12.3 â€‹± â€‹2.6 â€‹mmHg immediately post-procedure (P â€‹< â€‹0.001). At follow-up, one patient was found to have developed grade 2 hepatic encephalopathy thrice during the first year, according to the West Haven criteria. However, this was resolved following medical treatment. Conclusions: When the patient's portal venous anatomy is unconducive to the performance of TIPS using the transjugular approach, PTIPS can be considered as a safe, effective complementary surgical approach for patients with VB.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34809421

RESUMO

Exploring the hydrophobicity of robust conductors is significant for electronic devices to simultaneously be used in a wet environment and extreme conditions. However, a combination of conductivity, strong mechanical properties, and hydrophobicity in one material is hindered by the inherent features of the materials. A new kind of robust hydrophobic conductor is designed in transition-metal diborides (TMdBs: TiB2, ZrB2, and HfB2) to break through this challenge. The results calculated by density functional theory indicate that high hardness comes from high shear and bulk modulus, which is consistent with experimental results (TiB2, 25.0 GPa; ZrB2, 17.5 GPa; HfB2, 21.5 GPa). The theoretical calculated results reveal that edge sides have a lower surface energy than basal plane (001) in TMdBs. Hence, the edge sides are exposed with a needle-like morphology in TMdBs. Moreover, needle-like surfaces exhibiting hydrophobicity have water contact angles of 132.0° (TiB2), 116.8° (ZrB2), and 114.0° (HfB2). The hydrophobicity arises from a lower surface free energy of edge sides in TMdBs and a rough surface that reduces the contact area of water and a solid. This work develops a new kind of robust functional material in TMdBs.

17.
Chem Commun (Camb) ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34816823

RESUMO

Autophagy-based protein degradation is emerging as a promising technology for anti-diseases and innovative drug discovery. Here, we demonstrate a novel type of autophagy-targeting chimera (AUTAC) to degrade protein by targeting autophagy key protein LC3. The best compound 10f powerfully degraded BRD4 protein through the autophagy pathway and exhibited good anti-proliferative activity in multiple tumor cells, providing a powerful toolbox for medicinal chemists to study disease-related targets with autophagy-based degradation.

18.
Bioresour Technol ; : 126369, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838633

RESUMO

This study integrated spores and magnetite (Fe3O4) to form magnetic mycelium pellets (MMP) as bio-carriers immobilized with denitrifying bacteria in a bioreactor. Different carbon-to-nitrogen (C/N) ratios and hydraulic retention time (HRT) were established for investigating the performance of the bioreactor. The nitrate removal efficiency was 98.14% at C/N=2.0 and HRT=6 h. Gas chromatography (GC) results indicated that the main component of the produced gas was N2. Fe3O4 was well-integrated into MMP according to X-ray diffraction (XRD) results and infrared spectrometer (FTIR) analysis. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) showed that bacteria were successfully immobilized on MMP. Fluorescence excitation-emission matrix (EEM) indicated that functional bacteria GF2 might enhance the metabolic activity of the microbial community in the bioreactor and microbial activity was highest at C/N=2.0. Pseudomonas stutzeri sp. GF2 might be immobilized and had a major role in the bioreactor according to high throughput sequencing results.

19.
J Colloid Interface Sci ; 608(Pt 2): 1257-1267, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34739989

RESUMO

In this study, a series of one-dimensional (1D)/two-dimensional (2D) heterostructure hybrids were fabricated through the in situ growth of a Co and Ni bimetallic zeolitic imidazolate framework (CoNi-ZIF) around N-doped carbon nanotubes (N-CNTs). The hybrids were further exploited as effective supercapacitor materials. The N-CNTs were prepared by carbonizing a mixture of glucose and the melamine-cyanuric acid complex at a high temperature (900 °C) under N2 atmosphere and applied as the template for the in situ synthesis of CoNi-ZIF nanosheets (NSs). The 1D N-CNTs in the hybrids can act as the high-way for charge transfer to boost the faradaic reactions. Changing the usage of metal precursors not only provided abundant redox reaction sites in 2D CoNi-ZIF NSs but also modulated the microstructures and chemical components of the hybrids. The integration of the features of N-CNTs and CoNi-ZIF NSs can result in a synergistic effect between N-CNTs and CoNi-ZIF NSs. Therefore, the obtained CoNi-ZIFs and N-CNTs hybrid (CoNi-ZIF@N-CNT) exhibited superior electrochemical capacitive performance. Comparison revealed that the CoNi-ZIF@N-CNT-2 hybrid, which was prepared with a 1:1 mass ratio of Co(NO3)2·6H2O and Ni(NO3)2·6H2O, displayed the largest specific capacitance of 1118F g-1 at 1 A g-1, which was higher than the capacitance of most reported metal-organic framework (MOF)-based supercapacitor electrodes. Moreover, the asymmetric supercapacitor based on the CoNi-ZIF@N-CNT-2 electrode exhibited a high energy density of 51.1 Wh kg-1 at the power density of 860.1 W kg-1 and good cycle stability. This work can provide a facile and effective way for the fabrication of heterostructured 1D/2D nanostructures based on 2D MOFs for advanced energy storage.

20.
Front Cardiovasc Med ; 8: 750186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722681

RESUMO

Background: Doxorubicin (Dox) is one of the most effective chemotherapy agents used in the treatment of solid tumors and hematological malignancies. However, it causes dose-related cardiotoxicity that may lead to heart failure in patients. Luteolin (Lut) is a common flavonoid that exists in many types of plants. It has been studied for treating various diseases such as hypertension, inflammatory disorders, and cancer. In this study, we evaluated the cardioprotective and anticancer effects of Lut on Dox-induced cardiomyopathy in vitro and in vivo to explore related mechanisms in alleviating dynamin-related protein (Drp1)-mediated mitochondrial apoptosis. Methods: MTT and LDH assay were used to determine the viability and toxicity of cardiomyocytes treated with Dox and Lut. Flow cytometry was used to examine ROS levels, and electron and confocal microscopy was employed to assess the mitochondrial morphology. The level of apoptosis was examined by Hoechst 33258 staining. The protein levels of myocardial fission protein and apoptosis-related protein were examined using Western blot. Transcriptome analysis of the protective effect of Lut against Dox-induced cardiac toxicity in myocardial cells was performed using RNA sequencing technology. The protective effects of Lut against cardiotoxicity mediated by Dox in zebrafish were quantified. The effect of Lut increase the antitumor activity of Dox in breast cancer both in vitro and in vivo were further employed. Results: Lut ameliorated Dox-induced toxicity in H9c2 and AC16 cells. The level of oxidative stress was downregulated by Lut after Dox treatment of myocardial cells. Lut effectively reduced the increased mitochondrial fission post Dox stimulation in cardiomyocytes. Apoptosis, fission protein Drp1, and Ser616 phosphorylation were also increased post Dox and reduced by Lut. In the zebrafish model, Lut significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, in the mouse model, Lut prevented Dox-induced cardiotoxicity and enhanced the cytotoxicity in triple-negative breast cancer by inhibiting proliferation and metastasis and inducing apoptosis.

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