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In this work, various novel pyridinyl- and pyridinium-modified Aza-BODIPY PSs were designed and constructed based on monoiodo Aza-BODIPY PSs (BDP-4 and BDP-15) in an attempt to construct "structure-inherent organelles-targeted" PSs to endow potential organelle-targeting ability. Pyridinyl PSs displayed potent photodynamic efficacy, and monorigidified PSs were very effective. The monorigidified PS 20 with meta-pyridinyl moiety displayed the most potent photoactivity and negligible dark toxicity with a favorable dark/phototoxicity ratio (>4800). To our surprise, monorigidified PS with meta-pyridinyl moiety (e.g., 20) was lipid droplet-targeted. 20 showed good cellular uptake and intracellular ROS generation compared with BDP-15. The preliminary cell death process exploration indicated that 20 resulted in lipid peroxidation and induced cell death through an iron-independent ferroptosis-like cell death pathway. In vivo antitumor efficacy experiments manifested that 20 significantly inhibited tumor growth and outperformed BDP-15 and Ce6 even under a single low-dose light irradiation (30 J/cm2).
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Chemotherapy is one of the primary and indispensable intervention against cancers though it is always accompanied by severe side effects especially cachexia. Cachexia is a fatal metabolic disorder syndrome, mainly characterized by muscle loss. Oxidative stress is the key factor that trigger cachectic muscle loss by inducing imbalance in protein metabolism and apoptosis. Here, we showed an oral compound (Z526) exhibited potent alleviating effects on C2C12 myotube atrophy induced by various chemotherapeutic agents in vitro as well as mice muscle loss and impaired grip force induced by oxaliplatin in vivo. Furthermore, Z526 also could ameliorate C2C12 myotube atrophy induced by the combination of chemotherapeutic agents with conditioned medium of various tumor cells in vitro as well as mice muscle atrophy of C26 tumor-bearing mice treated with oxaliplatin. The pharmacological effects of Z526 were based on its potency in reducing oxidative stress in cachectic myocytes and muscle tissues, which inhibited the activation of NF-κB and STAT3 to decrease Atrogin-1-mediated protein degradation, activated the AKT/mTOR signaling pathway to promote protein synthesis, regulated Bcl-2/BAX ratio to reduce Caspase-3-triggered apoptosis. Our work suggested Z526 to be an optional strategy for ameliorating cachexia muscle atrophy in the multimodality treatment of cancers.
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Antineoplásicos , Apoptose , Caquexia , Atrofia Muscular , Estresse Oxidativo , Animais , Caquexia/tratamento farmacológico , Caquexia/patologia , Caquexia/induzido quimicamente , Caquexia/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/efeitos adversos , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Masculino , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , NF-kappa B/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Linhagem Celular Tumoral , Fator de Transcrição STAT3/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos BALB C , Linhagem Celular , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologiaRESUMO
Developing effective near-infrared (NIR) photosensitizers (PSs) has been an attractive goal of photodynamic therapy (PDT) for cancer treatment. In this study, we synthesized N, N-diethylaminomethylphenyl-containing Aza-BODIPY photosensitizers and comprehensively investigated their photophysical/photochemical properties, as well as cell-based and animal-based anti-tumor studies. Among them, BDP 1 has strong NIR absorption at 680 nm and higher singlet oxygen yield in PBS which showed favorable pH-activatable and lysosome-targeting ability. BDP 1 could be easily taken up by tumor cells and showed negligible dark activity (IC50 > 50 µM), however strong phototoxicity upon exposure to light irradiation. The acceptable fluorescence emission from BDP 1 allowed convenient in vivo fluorescence imaging for organ distribution studies in mice. After PDT treatment with upon single time PDT treatment at the beginning using relatively low light dose (54 J/ cm2), BDP 1 (2 mg/kg, 0.1 mL) was found to have strong efficacy to inhibit tumor growth and even to ablate off tumor without causing body weight loss. Therefore, pH-activatable and lysosome-targeted PS may become an effective way to develop potent PDT agent.
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Neoplasias , Fotoquimioterapia , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Compostos de Boro/química , Neoplasias/tratamento farmacológico , LisossomosRESUMO
Collagen is abundant but exposed in tumor due to the abnormal tumor blood vessels, thus is considered as a tumor-specific target. The A3 domain of von Willebrand factor (vWF A3) is a kind of collagen-binding domain (CBD) which could bind collagen specifically. Previously we reported a chemosynthetic CBD-SIRPαFc conjugate, which could block CD47 and derived tumor-targeting ability by CBD. CBD-SIRPαFc conjugate represented improved anti-tumor efficacy with increased MHC II+ M1 macrophages, but the uncertain coupling ratio remained a problem. Herein, we produced a vWF A3-SIRPαFc fusion protein through eukaryotic expression system. It was examined at both molecular and cellular levels with its collagen affinity, uninfluenced original affinity to targets and phagocytosis-promoting function compared to unmodified SIRPαFc. Living imaging showed that vWF A3-SIRPαFc fusion protein derived the improved accumulation and retention in tumor than SIRPαFc. In the MC38 allograft model, vWF A3-SIRPαFc demonstrated a superior tumor-suppressing effect, characterized by increased MHC II+ M1 macrophages and T cells (particularly CD4+ T cells). These results revealed that vWF A3-SIRPαFc fusion protein derived tumor-targeting ability, leading to improved anti-tumor immunotherapeutic efficacy compared to SIRPαFc. Altogether, vWF A3 improved the anti-tumor efficacy and immune-activating function of SIRPαFc, supporting targeting tumor collagen as a possible targeted strategy.
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Neoplasias , Fator de von Willebrand , Sítios de Ligação , Fator de von Willebrand/química , Fator de von Willebrand/metabolismo , Colágeno/metabolismo , Fagocitose , Imunoterapia , Ligação Proteica , Neoplasias/terapiaRESUMO
Mito-tracker deep red (MTDR) as a commercially available mitochondria-targeting probe was easily bleached upon imaging. We designed and synthesized a family of meso-pyridinium BODIPY and introduced lipophilic methyl or benzyl as the head moiety to develop a mitochondria-targeting deep red probe. Moreover, we changed the substitution of the 3,5-phenyl moieties with the methoxy or methoxyethoxyethyl group to balance hydrophilicity. The designed BODIPY dyes possessed long absorption and good fluorescence emission. Among them, meso ortho-pyridinium BODIPYs with benzyl head and glycol substitution on phenyl moiety (3h) with favorable Stokes shift were found to have the best mitochondrial targeting performance. 3h was easily uptaken by cells and was less toxic and more photostable than MTDR. An immobilizable probe (3i) was further developed, and nice mitochondria targeting properties under the damaging condition of mitochondria membrane potential were maintained. BODIPY 3h or 3i may become alternative long-wavelength mitochondria targeting probes apart from MTDR and be suitable for long-term mitochondrial tracking studies.
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Compostos de Boro , Corantes Fluorescentes , Humanos , Células HeLa , MitocôndriasRESUMO
In order to develop and optimize nano drug delivery systems (NDDSs), it is crucial to understand their in vivo fate. We previously found that P2 (Aza-BODIPY) and P4 (BODIPY) as aggregation-caused quenching (ACQ) probes could be used to unravel the biofate of various nanoparticles owing to their water-sensitive emission. However, previous studies also found that quenched ACQ probe aggregates showed repartition into hydrophobic physiologically relevant constituents, resulting in fluorescence re-illumination. In this paper, we screened various types of fluorophores for ACQ and their re-illumination performance and focused on Aza-BODIPY dyes. BODIPY and Aza-BODIPY dyes were identified to be advantageous over other fluorophores. Some BODIPY and Aza-BODIPY dyes were selected as potential probes with improved performance against re-illumination. The best performing probes were Aza-C7 and Aza-C8. Aza-C7-loaded PMs were found to have decreased fluorescence re-illumination properties over P2 and DiR.
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Compostos de Boro , Sistemas de Liberação de Fármacos por Nanopartículas , Compostos de Boro/química , Corantes Fluorescentes/químicaRESUMO
In this study, we linked classical organelle-targeting groups, such as triphenylphosphonium, pentafluorobenzene, and morpholine, to our previously reported potent monoiodo Aza-BODIPY photosensitizer (BDP-15). They were conveniently prepared and retained the advantages of Aza-BODIPY PS with intense NIR absorption, moderate quantum yield, potent photosensitizing efficiency, and good stability. The in vitro antitumor assessment indicated that mitochondria-targeting and lysosome-targeting groups were more effective than ER-targeting groups. Considering undesirable dark toxicity of triphenylphosphonium-modified PSs, compound 6 containing amide-linked morpholine possessed a favorable dark/phototoxicity ratio (>6900 for tumor cells) and was localized in lysosomes with Pearson's coefficient of 0.91 to Lyso-Tracker Green DND-26. 6 exhibited significantly increased intracellular ROS production and resulted in early/late apoptosis and necrosis to disrupt tumor cells. Moreover, in vivo antitumor efficacy exploration suggested that even under a slightly low dose of light (30 J/cm2) and single-time photoirradiation, 6 retarded tumor growth dramatically and displayed much better PDT activity over BDP-15 and Ce6.
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Dermatite Fototóxica , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/efeitos da radiação , Fotoquimioterapia/métodos , Compostos de Boro/farmacologia , Compostos de Boro/efeitos da radiação , Lisossomos , Dermatite Fototóxica/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Abnormal intracellular peroxynitrite (ONOO-) concentration is related to oxidative damage, which is correlated with many pathological consequences, such as local inflammation and other diseases. In this work, a series of resorufin benzyl ether-based fluorescent probes were designed using boronate as a recognizing moiety installed on a phenyl moiety for ONOO- detection via a self-immolation mechanism. The location of the boronate as well as the substitution patterns on the phenyl moiety were investigated and the responding behaviors of the designed probes to ONOO-, other reactive oxygen species, and biothiols were examined. It was found that all the immolative probes were inevitably dominated by ONOO-. Compared with other probes, p-Borate possessed favorable selectivity and high sensitivity to ONOO-. Moreover, p-Borate was successfully used to detect ONOO- in cells and inflamed mice.
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Boratos , Corantes Fluorescentes , Camundongos , Animais , Ácido Peroxinitroso , Espécies Reativas de Oxigênio , Estresse OxidativoRESUMO
Due to the overwhelming percentage of poorly water-soluble drugs, pharmaceutical industry is in urgent need of efficient approaches for solubilization and permeability improvement. Salts consisting of lipophilic fatty acid anions and hydrophilic choline cations are found to be surface active and able to form ionic co-aggregates (ICAs) in water. Choline oleate-based ICAs significantly enhance oral absorption of paclitaxel (PTX) as compared with cremophor EL-based micelles (MCs). Aggregation-caused quenching probes enable tracking of intact ICAs in in vivo transport and cellular interaction. Prolonged intestinal retention of ICAs than MCs implies stronger solubilizing capability in vivo. Ex vivo imaging of major organs and intestinal tracts suggests transepithelial transport of intact ICAs. Cellular studies support the enhanced absorption of PTX and transmembrane transport of intact ICAs. In conclusion, ICAs, consisting of lipophilic ions and hydrophilic counter-ions, are of great potential in delivery of poorly water-soluble drugs by enhancing solubility and permeability.
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The identification of sentinel lymph node (SLN) is an important method for prognostic evaluation and minimally invasive staging of metastatic tumors. Here, we report a series of near-infrared fluorescent heptamethylamine dyes (series A, B and C) with central cycloalkene ring modified by tyrosine or N-Boc tyrosine via ether linkage. N-Boc tyrosine/tyrosine modification provided enhanced absorption coefficient and fluorescence quantum yield in DMSO, however with slight hypsochromic shift compared to the mother dyes in DMSO. In PBS, series A and B were found to be more fluorescent than ICG and showed brighter images. Compound A1 was found to exhibit the most favorable imaging performance among all the dyes investigated and was selected for in vivo sentinel lymph node mapping experiments in mice. A1 showed faster response and stronger fluorescence emission than FDA-approved ICG. The lymph node tracing with A1 could be assisted by MB staining. Ex vivo imaging of harvested organs indicated that similar metabolic characteristics of A1 and ICG. Overall, A1 is advantageous over ICG and is very promising for non-invasive lymph node imaging.
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Biópsia de Linfonodo Sentinela , Linfonodo Sentinela , Animais , Corantes , Dimetil Sulfóxido , Corantes Fluorescentes , Verde de Indocianina , Camundongos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Tirosina , ÁguaRESUMO
Aza-dipyrromethene boron difluoride (Aza-BODIPY) dyes have attracted much interest in recent decades. In this manuscript, we provide a facile way to access pyridine-substituted pyrroles. A series of 1/7-pyridinyl and pyridinium near-infrared (NIR) Aza-BODIPYs with/without rigidity were constructed and their spectroscopic properties were extensively investigated. These pyridinyl Aza-BOIDIPYs displayed slight bathochromic shifts and maintained bright NIR emission. Pyridinium Aza-BODIPYs showed increased bathochromic shift, however, the molar extinction coefficients and fluorescence quantum yields were decreased owing to ICT effect. The impacts followed the order of pyridin-4-ium>pyridin-2-ium>pyridin-3-ium, which was in consistence with their ICT strength. MO calculation was performed to provide possible explanation to the red-shifted absorption/emission, and apparent charge separation in pyridin-4-ium Aza-BODIPYs. The pyridinium Aza-BODIPY localized in lysosome and potentially avoided harmful ''alkalinizing effects'' of traditional lysosome-targeting fluorescent dyes containing amine moiety. We are working on construction of pyridinyl and pyridinium Aza-BODIPY photosensitizers against microbials or tumors.
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Corantes Fluorescentes , Pirróis , Aminas , Compostos de Boro/química , Fluorescência , Corantes Fluorescentes/química , Fármacos Fotossensibilizantes , Piridinas , Pirróis/químicaRESUMO
Lysosomes are important organelles in physiological and pathological processes. It is of great significance to understand the mechanism of lysosome and monitor its movement and action at cellular level. Traditional lysosome trackers include Lyso-Tracker Green and Lyso-Tracker Red. However, both of them are tend to be photobleached easily and affected by pH variation, which is not conducive for long-term and real-time tracing of lysosomes in changeable environment. Herein, we designed a series of meso amide BODIPY based lysosome-targeting fluorescent probes. It was discovered that introduction of methyl group on amide is able to change the fluorescence characteristics of meso amide BODIPY. Among BODIPYs developed, Lyso-Me-1 exhibited outstanding lysosome-targeting ability in comparison with Lyso-Tracker Green confirmed by confocal microscope colocalization experiment. Moreover, continuous scanning of confocal microscope demonstrated that Lyso-Me-1 displayed improved photostability compared with Lyso-Tracker Green and Lyso-Tracker Red.
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Amidas , Corantes Fluorescentes , Compostos de Boro , LisossomosRESUMO
The discovery of novel photosensitizers with potent phototoxicity and desirable water solubility is an urgent task for photodynamic therapy. Herein, a series of amino acid-modified aza-BODIPY photosensitizers were synthesized and evaluated. These new PSs exhibited enhanced aqueous solubility, increased 1O2 generation efficiency, and an improved photo-dark toxicity ratio. Aspartic acid-modified PS of 1a, which possessed intense NIR absorption and high 1O2 quantum yield, demonstrated the most potent efficacy toward the investigated tumor cell lines without using an emulsifier. Subcellular localization, cell-based ROS production, and cell death pathway of 1a were studied. In vivo fluorescence imaging and ex vivo organ distribution assays manifested that 1a possessed reasonable distribution and clearance. In vivo PDT studies indicated that 1a revealed advantages over Ce6 and our previously optimized PS of BDP-4. It not only afforded an excellent PDT effect with a low drug dose under only single-time photoirradiation but also induced an antitumor immunological response.
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Aminoácidos/química , Compostos de Boro/síntese química , Compostos de Boro/farmacologia , Melanoma/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Animais , Ácido Aspártico/química , Linhagem Celular Tumoral , Descoberta de Drogas , Feminino , Humanos , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio , Relação Estrutura-Atividade , Frações Subcelulares/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Degradation of neonicotinoid insecticide dinotefuran (DIN) in dielectric barrier discharge (DBD) non-thermal plasma combined with lanthanum-doped titanium dioxide (La-TiO2) system was investigated. A La-TiO2 catalyst was prepared by the sol-gel method and characterized by SEM, XRD, and DRS. The effects of various factors (initial concentration, initial pH, input power, and addition of metal ions) on the removal rate of DIN were evaluated. The results indicated that when the initial concentration, input power, initial pH, and Fe2+ catalyst ions were 100â mg/L, 150 W, 10.5 and 50â mg/L, respectively, the DIN degradation efficiency was improved to 99.0% by coupling 10â wt% La-TiO2 at 180 min. La-TiO2 showed excellent catalytic performance on DIN degradation in a DBD system. The removal rate decreased with the presence of H2O2 and a scavenger, manifesting that HOâ plays an imperative role in the degradation process. Furthermore, intermediate products were analyzed by MS and the possible degradation pathway of DIN was proposed.
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Peróxido de Hidrogênio , Lantânio/química , Titânio , Catálise , Guanidinas , Peróxido de Hidrogênio/química , Neonicotinoides , Nitrocompostos , Titânio/químicaRESUMO
Antimicrobial photodynamic therapy (aPDT) has emerged as a novel and promising approach for the treatment of pathogenic microorganism infections. The efficacy of aPDT depends greatly on the behavior of the photosensitizer. Herein, we report the design, preparation, antimicrobial photodynamic activities, as well as structure-activity relationships of a series of photosensitizers modified at the meso position of a 1,3,5,7-tetramethyl BODIPY scaffold with various pyridinyl and pyridinium moieties. The photodynamic antimicrobial activities of all photosensitizers have been tested against Staphylococcus aureus, Escherichia coli, Candida albicans, and Methicillin-resistant S. aureus (MRSA). The methyl meso-(meta-pyridinium) BODIPY photosensitizer (3c) possessed the highest phototoxicity against these pathogens at minimal inhibitory concentrations (MIC) ranging from 0.63 to 1.25 µM with a light dose of 81 J/cm2. Furthermore, 3c exhibited an impressive antimicrobial efficacy in S. aureus-infected mice wounds. Taken together, these findings suggest that 3c is a promising candidate as the antimicrobial photosensitizer for combating pathogenic microorganism infections.
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Anti-Infecciosos/farmacologia , Compostos de Boro/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Anti-Infecciosos/química , Compostos de Boro/química , Candida albicans/efeitos dos fármacos , Linhagem Celular Transformada , Relação Dose-Resposta à Radiação , Escherichia coli/efeitos dos fármacos , Humanos , Técnicas In Vitro , Luz , Camundongos , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Self-microemulsifying drug delivery systems (SMEDDSs) have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules. However, information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare. Aggregation-caused quenching (ACQ) fluorescent probes are utilized to visualize the in vivo behaviors of SMEDDSs, because the released probes during lipolysis are quenched upon contacting water. Two SMEDDSs composed of medium chain triglyceride and different ratios of Tween-80 and PEG-400 are set as models, meanwhile Neoral® was used as a control. The SMEDDS droplets reside in the digestive tract for as long as 24 h and obey first order kinetic law of lipolysis. The increased chain length of the triglyceride decreases the lipolysis of the SMEDDSs. Ex vivo imaging of main tissues and histological examination confirm the trans-epithelial transportation of the SMEDDS droplets. Approximately 2%-4% of the given SMEDDSs are transported via the lymph route following epithelial uptake, while liver is the main termination. Caco-2 cell lines confirm the cellular uptake and trans-epithelial transport. In conclusion, a fraction of SMEDDSs can survive the lipolysis in the gastrointestinal tract, permeate across the epithelia, translocate via the lymph, and accumulate mainly in the liver.
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In vitroâin vivo correlation (IVIVC) of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients. Nevertheless, in vivo dissolution profiles have never been accurately portrayed. The current practice of IVIVC has to resort to in vivo absorption fractions (F a). In this proof-of-concept study, in vivo dissolution of a model poorly water-soluble drug fenofibrate (FNB) was investigated by fluorescence bioimaging. FNB crystals were first labeled by near-infrared fluorophores with aggregation-caused quenching properties. The dyes illuminated FNB crystals but quenched immediately and absolutely once been released into aqueous media, enabling accurate monitoring of residual drug crystals. The linearity established between fluorescence and crystal concentration justified reliable quantification of FNB crystals. In vitro dissolution was first measured following pharmacopoeia monograph protocols with well-documented IVIVC. The synchronicity between fluorescence and in vitro dissolution of FNB supported using fluorescence as a measure for determination of dissolution. In vitro dissolution correlated well with in vivo dissolution, acquired by either live or ex vivo imaging. The newly established IVIVC was further validated by correlating both in vitro and in vivo dissolution with F a obtained from pharmacokinetic data.
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Together, the number of waves, wave vectors, amplitudes, and additional phases constitute the coherent wave group configuration and determine the pattern of the interference field. Identifying an appropriate wave group configuration is key to generating vortex lattices via interferometry. Previous studies have approached this task by first assigning the four elements, then calibrating the vortex state of the interference field. However, this method has failed to progress beyond generating third-order vortex lattices, which are insufficient for some practical applications. Therefore, this study proposes a method for determining the proper wave group configurations corresponding to arbitrary-order vortex lattices. We adopt a goal-driven approach: First, we set a vortex lattice as the target field and model it, before decomposing the target field into a sum of multiple harmonics using Fourier transforms. These harmonics constitute the wave group required to generate the target vortex lattice. As vortex lattices of any order can be set as the target field, the proposed method is compatible with any mode order. Simulations and experiments were conducted for fourth- and fifth-order vortex lattices, thus demonstrating the effectiveness of the proposed method.
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ABSTRACT: Dysfunction of vascular smooth muscle cells (VSMCs) assumes a fundamental part in the pathogenesis of atherosclerosis (AS). Circular RNA granulin precursor (circ_GRN) was identified to promote the proliferation and invasion of human VSMCs (HVSMCs) in an in vitro AS model. However, the underlying mechanisms remain unclear. Levels of circ_GRN, microRNA (miR)-214-3p, and forkhead box protein O1 (FOXO1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. The proliferation, migration, and inflammatory response of HVSMCs were evaluated by using flow cytometry, colony formation, Cell Counting Kit-8, Western blot, transwell assays, and enzyme-linked immunosorbent assay, respectively. The binding interaction between miR-214-3p and circ_GRN or FOXO1 was detected by dual-luciferase reporter assay. In this study, we found that circ_GRN was elevated in the serum of AS and oxidized low-density lipoprotein (ox-LDL)-induced HVSMCs. The in vitro AS model was established by exposing HVSMCs to ox-LDL, and we found circ_GRN knockdown reversed ox-LDL-evoked cell proliferation, migration, and inflammation. In a mechanical study, miR-214-3p directly bound to circ_GRN or FOXO1, and circ_GRN could regulate FOXO1 expression by competitively binding to miR-214-3p. Importantly, we demonstrated that miR-214-3p inhibition attenuated the protective effects of circ_GRN knockdown on ox-LDL-induced HVSMCs; besides that, miR-214-3p overexpression abolished ox-LDL-triggered HVSMC proliferation, migration, and inflammation, which were counteracted by FOXO1 upregulation. In conclusion, circ_GRN promoted the proliferation, migration, and inflammation of HVSMCs through miR-214-3p/FOXO1 axis in ox-LDL-induced AS model in vitro, suggesting the potential involvement in an AS process, which provided a potential candidate for future clinic intervention in AS.
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Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Proteína Forkhead Box O1/metabolismo , Mediadores da Inflamação/metabolismo , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , RNA Circular/metabolismo , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Estudos de Casos e Controles , Células Cultivadas , Proteína Forkhead Box O1/genética , Regulação da Expressão Gênica , Humanos , Lipoproteínas LDL/toxicidade , MicroRNAs/genética , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , RNA Circular/genética , Transdução de Sinais , Remodelação VascularRESUMO
This work investigated the preparation of Ti/Sb-SnO2 electrode co-doped with graphene and europium and the electrochemical degradation of clothianidin in aqueous solution with Ti/Sb-SnO2-Eu&rGO electrode. The physicochemical properties of different electrodes were characterized by using the scanning electron microscopy, X-ray diffraction, oxygen evolution potential and cyclic voltammetry tests. The results indicated that the Ti/Sb-SnO2-Eu&rGO electrodes have a compact structure and fine grain size and have a higher oxygen evolution overpotential than Ti/Sb-SnO2-None, Ti/Sb-SnO2-Eu and Ti/Sb-SnO2-rGO electrodes. Among the four electrodes, the Ti/Sb-SnO2-Eu&rGO electrode showed the highest efficiency and was chosen as the experimental electrode. The main influence factors on the degradation of clothianidin, such as initial pH, electrolyte concentration, current density and initial concentration of clothianidin, were analyzed. The results showed that the removal rate of clothianidin can reach 96.44% under the optimal conditions for 120 min treatment. Moreover, a possible degradation pathway including the fracture of internal bonds of clothianidin such as the N-N bond, the C-N bond that connects nitroguanidine to the thiazole ring and mineralization was elucidated by intermediate products identified by HPLC-MS method and Fourier transform infrared spectroscopy (FTIR). This paper introduces the Ti/Sb-SnO2-Eu&rGO electrode into an electrocatalytic degradation system and could provide basic data and technique support and guidance for the clothianidin wastewater pollution control.