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1.
Molecules ; 29(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38930884

RESUMO

Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of D-mannitol-cerium-quercetin/rutin coordination polymer nanoparticles (MCQ/R NPs) as a potential treatment for ALI. The MCQ/R NPs, which integrate rutin and quercetin for their therapeutic potential and D-mannitol for its pulmonary targeting, displayed exceptional efficacy. By utilizing cerium ions for optimal nanoparticle assembly, the MCQ/R NPs demonstrated an average size of less than 160 nm. Impressively, these nanoparticles outperformed conventional treatments in both antioxidative capabilities and biocompatibility. Moreover, our in vivo studies on LPS-induced ALI mice showed a significant reduction in lung tissue inflammation. This groundbreaking research presents MCQ/R NPs as a promising new approach in ALI therapeutics.


Assuntos
Lesão Pulmonar Aguda , Cério , Manitol , Nanopartículas , Polímeros , Quercetina , Lesão Pulmonar Aguda/tratamento farmacológico , Quercetina/farmacologia , Quercetina/química , Animais , Manitol/química , Manitol/uso terapêutico , Nanopartículas/química , Camundongos , Polímeros/química , Cério/química , Cério/farmacologia , Cério/uso terapêutico , Rutina/química , Rutina/farmacologia , Rutina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/química , Humanos , Sinergismo Farmacológico , Modelos Animais de Doenças , Lipopolissacarídeos
2.
Small ; 19(43): e2302829, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37356081

RESUMO

Herein, a direct-contact photocurrent-direction-switching photoelectrochemical (PEC) biosensing platform for the ultrasensitive and selective detection of soluble CD146 (sCD146) is reported for the first time via in situ formation of carbon nitride quantum dots (CN QDs)/titanium dioxide (TiO2 ) nanodiscs with the double-supported 3D DNA walking amplification. In this platform, metal organic frameworks (MOFs)-derived porous TiO2 nanodiscs exhibit excellent anodic photocurrent, whereas a single-stranded auxiliary DNA (ssDNA) as biogate is absorbed onto the TiO2 nanodiscs to block active sites. Subsequently, with the help of intermediate DNAs from target sCD146-induced double-supported 3D DNA walking signal amplification, the ssDNA can leave away from the surface of TiO2 nanodiscs due to the specific hybridization with intermediate DNAs. Afterward, the successful direct contact of CN QDs on TiO2 nanodiscs by porosity and electrostatic adsorption, leads to the effective photocurrent-direction switching from anodic to cathodic photocurrent. Based on direct-contact photocurrent-direction-switching CN QDs/TiO2 nanodiscs system and double-supported 3D DNA walking signal amplification, sCD146 is detected sensitively with a wide linear range (10 fg mL-1 to 5 ng mL-1 ) and a low limit of detection (2.1 fg mL-1 ). Also, the environmentally friendly and direct-contact photocurrent-direction-switching PEC biosensor has an application prospect for cancer biomarker detection.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Pontos Quânticos/química , Técnicas Eletroquímicas/métodos , Titânio/química , DNA , DNA de Cadeia Simples , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , Limite de Detecção
3.
Mol Cell Biochem ; 478(5): 1031-1044, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36214894

RESUMO

Protein arginine methyltransferase 5 (PRMT5) is overexpressed in lung carcinoma, which promotes tumor cell proliferation, survival, migration and invasion. Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling, which are mainly used to stop in cancer pain and bleeding. Here we found that cell viability and colony formation were inhibited after the incubation of AMI-1. Meanwhile, AMI-1 suppressed cell migration, enhanced apoptosis, induced cell cycle arrest, inhibited PRMT5 expression and histone H3R8 and H4R3 symmetric di-methylation (H3R8me2s and H4R3me2s) accumulation, down-regulated the expression of eukaryotic translation initiation factor 4E (eIF4E) in lung carcinoma cells. Moreover, AMI-1 suppressed tumor growth, decreased H3R8me2s and H4R3me2s accumulation, down-regulated eIF4E expression and increased p53 expression in lung carcinoma xenografts of BALB/c nude mice. Of note, combined and CKI markedly enhanced the anticancer efficacy CKI in lung carcinoma. The above findings demonstrated that AMI-1 has established antineoplastic activity and this role may be associated with affecting the function of eIF4E via inhibiting PRMT5 activity or protein levels in lung carcinoma. This study highlights evidence of novel selective anticancer activity of AMI-1 in combination with CKI in lung carcinoma.


Assuntos
Antineoplásicos , Carcinoma , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Fator de Iniciação 4E em Eucariotos/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Camundongos Nus , Proteína-Arginina N-Metiltransferases/genética
4.
Toxicol Appl Pharmacol ; 435: 115829, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34919946

RESUMO

Type I co-activator-associated arginine methyltransferase 1 (CARM1) and type II protein arginine methyltransferase 5 (PRMT5) are highly expressed in multiple cancers including liver cancer and their overexpression contributes to poor prognosis, thus making them promising therapeutic targets. Here, we evaluated anti-tumor activity of ribavirin in hepatocellular carcinoma (HCC). We found that ribavirin significantly inhibited the proliferation of HCC cells in a time- and dose-dependent manner. Furthermore, ribavirin suppressed the growth of subcutaneous and orthotopic xenograft of HCC in mice, decreased vascular endothelial growth factor (VEGF) and peritoneal permeability to reduce ascites production, and prolonged the survival of mice in HCC ascites tumor models. Mechanistically, ribavirin potently down-regulated global protein expression of CARM1 and PRMT5, and concurrently decreased accumulation of H3R17me2a and H3R8me2s/H4R3me2s. However, ribavirin did not affect the activity and mRNA levels of both CARM1 and PRMT5 in vivo and in vitro HCC cells. In addition, our ChIP results shown that ribavirin inhibited CARM1 which in turn decreased the H3R17me2a, binds to the eukaryotic translation initiation factor 4E (eIF4E) and VEGF promoter region, and reduced the relative mRNA expression level of eIF4E and VEGF in HCC cells. Our findings suggested a potential therapeutic strategy for patients with HCC through inhibition of the abnormal activation/expression of both CARM1 and PRMT5.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Ascite/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Ribavirina/farmacologia , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Fator de Iniciação 4E em Eucariotos/biossíntese , Fator de Iniciação 4E em Eucariotos/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteína-Arginina N-Metiltransferases/genética , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Anal Chem ; 93(45): 15200-15208, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34723514

RESUMO

Exosome concentration and exosomal proteins are regarded as promising cancer biomarkers. Herein, a waxberry-like magnetic bead (magnetic-nanowaxberry) which has huge surface area and strong affinity was synthesized to couple with aptamer for exosome capture and recovery. Subsequently, we developed a fluorescent assay for the sensitive, accurate, and simultaneous quantification of exosome and cancer-related exosomal proteins [epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM)] by using triple-colored probes to recognize EGFR and EpCAM or spontaneously anchor to the lipid bilayer. In this design, the interference of soluble proteins can be avoided due to the dual recognition strategy. Moreover, the lipid-based quantification of exosome concentration can improve the accuracy. Besides, the simultaneous detection mode can save samples and simplify the operation steps. Consequently, the assay shows high sensitivity (the limits of detection are down to 0.96 pg/mL for EGFR, 0.19 pg/mL for EpCAM, and 2.4 × 104 particles/µL for exosome), high specificity, and satisfactory accuracy. More importantly, this technique is successfully used to analyze exosomes in plasma to distinguish cancer patients from healthy individuals. To improve the diagnostic efficacy, the deep learning was used to exploit the potential pattern hidden in data obtained by the proposed method. Also, the accuracy for the intelligent diagnosis of cancer can achieve 96.0%. This study provides a new avenue for developing new biosensors for exosome analysis and intelligent disease diagnosis.


Assuntos
Técnicas Biossensoriais , Exossomos , Neoplasias , Biomarcadores Tumorais , Aprendizado Profundo , Humanos , Fenômenos Magnéticos
6.
Toxicol Appl Pharmacol ; 415: 115450, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33577917

RESUMO

Eukaryotic translation initiation factor 4E (eIF4E) and protein arginine methyltransferase 5 (PRMT5) are frequently overexpressed in colorectal cancer (CRC) tissues and associated with poor prognosis. Ribavirin, the only clinically approved drug known to target eIF4E, is an anti-viral molecule currently used in hepatitis C therapy. The potential of ribavirin to treat CRC remains largely unknown. Ribavirin treatment in CRC cell lines drastically inhibited cell proliferation and colony formation, induced S phase arrest and reduced cyclin D1, cyclin A/E and proliferating cell nuclear antigen (PCNA) levels in vitro, and suppressed tumorigenesis in mouse model of colitis-associated CRC. Mechanistically, ribavirin treatment significantly reduced PRMT5 and eIF4E protein levels and the accumulation of symmetric dimethylation of histone 3 at arginine 8 (H3R8me2s) and that of histone 4 at arginine 3 (H4R3me2s). Importantly, inhibition of PRMT5 by ribavirin resulted in promoted H3R8 methylation in eIF4E promoter region. Our results demonstrate the anti-cancer efficacy of ribavirin in CRC and suggest that the anti-cancer efficacy of ribavirin may be mediated by downregulating PRMT5 levels but not its enzymatic activity.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Metilação de DNA/efeitos dos fármacos , Fator de Iniciação 4E em Eucariotos/metabolismo , Histonas/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Ribavirina/farmacologia , Animais , Neoplasias Associadas a Colite/tratamento farmacológico , Neoplasias Associadas a Colite/enzimologia , Neoplasias Associadas a Colite/genética , Neoplasias Associadas a Colite/patologia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação para Baixo , Fator de Iniciação 4E em Eucariotos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Camundongos Endogâmicos ICR , Regiões Promotoras Genéticas , Proteína-Arginina N-Metiltransferases/genética , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos
7.
Anal Chem ; 90(15): 9480-9486, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29992808

RESUMO

Taking the zeolitic imidazolate framework (ZIF-67) as the precursor, p-type semiconducting Co3O4-Au polyhedra were synthesized and used as the signal amplifier to construct a sensitive photoelectrochemical (PEC) sensor for caspase-3 activity assay. Here, the n-type semiconductor Bi2S3-modified indium-tin oxide (ITO) slice was used as the photoelectrode. After immobilization of the biotin-DEVD-peptide (biotin-Gly-Asp-Gly-Asp-Glu-Val-Asp-Cys) onto the Bi2S3 surface, the streptavidin-labeled Co3O4-Au polyhedra were introduced to the sensing platform via the specific interaction between biotin and streptavidin. The Co3O4-Au polyhedra can not only quench the photocurrent of the Bi2S3 because of the competitive consumption of electron donors and exciting light energy (p-n-type semiconductor quenching effect), but also act as peroxidase mimetics to produce catalytic precipitate. Additionally, the steric hindrance effect from the Co3O4-Au polyhedra will decrease the PEC response of the Bi2S3. Ingeniously, the precipitates can not only deposit on the ITO electrode to decrease the photocurrent of PEC sensor, but also act as electron acceptors to scavenge the photogenerated electrons of Co3O4-Au polyhedra, leading to enhanced quenching ability of the Co3O4-Au polyhedra. When caspase-3 exists, caspase-3 can specifically recognize and cleave the biotin-DEVD-peptide, resulting in the increase of PEC response. Based on the multifunctional Co3O4-Au polyhedra, caspase-3 is detected sensitively with a linear range from 0.5 to 50 ng mL-1 and limit of detection down to 0.10 ng mL-1. The Co3O4-Au polyhedra provide a novel signal amplifier to construct PEC sensing platform and may have potential applications in bioanalysis, disease diagnostics, and clinical biomedicine.

8.
Analyst ; 143(12): 2799-2806, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29862398

RESUMO

The sensitive and specific determination of nucleic acids is very important in clinical diagnosis and biological studies. In this work, an ultrasensitive photoelectrochemical (PEC) biosensor has been developed for DNA detection based on a "signal-on" sensing strategy and a three-stage cascade signal amplification method (catalytic hairpin assembly (CHA), hybridization chain reaction (HCR) and alkaline phosphatase (ALP)-triggered in situ generation of ascorbic acid (AA)). Here, CHA hairpin 1 (CHA-HP1) is opened by the target DNA (T-DNA) owing to the hybridization between T-DNA and CHA-HP1, and then the opened CHA-HP1 hybridizes with CHA hairpin 2 (CHA-HP2) to displace the T-DNA, generating a CHA-HP1/CHA-HP2 complex. The displaced T-DNA triggers the next cycle of CHA, resulting in the generation of numerous CHA-HP1/CHA-HP2 complexes. Subsequently, one end of the CHA-HP1/CHA-HP2 complex hybridizes with the capture DNA immobilized on the indium tin oxide/TiO2/CdS : Mn electrode. After the introduction of dual-biotin labeled HCR hairpin 1 (HCR-HP1-Bio) and dual-biotin labeled HCR hairpin 2 (HCR-HP2-Bio), the other end of the CHA-HP1/CHA-HP2 complex opens HCR-HP1-Bio. The opened HCR-HP1-Bio triggers the HCR reaction between HCR-HP1-Bio and HCR-HP2-Bio, leading to the formation of long nicked duplex DNA structures. The dual-biotin modified HCR-hairpins can anchor more streptavidin-ALP to catalyze 2-phospho-l-ascorbic acid trisodium salt to yield more AA, leading to a larger PEC response. The proposed PEC biosensor shows superior analytical performance for T-DNA detection with a linear response ranging from 0.1 fM to 100 pM and a detection limit of 0.052 fM, and may provide a powerful biosensing platform for bioanalysis and early disease diagnosis.


Assuntos
Técnicas Biossensoriais , DNA/análise , Hibridização de Ácido Nucleico , Biotina , Técnicas Eletroquímicas , Limite de Detecção , Processos Fotoquímicos , Estreptavidina
10.
Planta ; 243(3): 719-31, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26669597

RESUMO

MAIN CONCLUSION: Phosphorylation and dephosphorylation events were initiated in wheat scab resistance. The putative FHB-responsive phosphoproteins are mainly involved in three functional groups and contain at least one tyrosine, serine, or threonine phosphorylation site. Fusarium head blight (FHB), caused by Fusarium graminearum, is a severe disease in wheat. Protein phosphorylation plays an important role in plant-pathogen interactions, however, a global analysis of protein phosphorylation in response to FHB infection remains to be explored. To study the effect of FHB on the phosphorylation state of wheat proteins, proteins extracted from spikes of a resistant wheat cultivar after 6 h of inoculation with F. graminearum or sterile H2O were separated by two-dimensional gel electrophoresis, and then the immunodetection of putative phosphoproteins was conducted by Western blotting using specific anti-phosphotyrosine antibody, anti-phosphothreonine antibody and anti-phosphoserine antibody. A total of 35 phosphorylated signals was detected and protein identities of 28 spots were determined. Functional categorization showed that the putative FHB-responsive phosphoproteins were mainly involved in defense/stress response, signal transduction, and metabolism. The phosphorylation status of proteins associated with signaling pathways mediated by salicylic acid, calcium ions, small GTPase, as well as with detoxification, reactive oxygen species scavenging, antimicrobial compound synthesis, and cell wall fortification was regulated in wheat spikes in response to F. graminearum infection. The present study reveals dynamics of wheat phosphoproteome in response to F. graminearum infection and suggests an important role of protein Ser/Thr/Tyr phosphorylation in fundamental mechanisms of wheat scab resistance.


Assuntos
Resistência à Doença , Fusarium/fisiologia , Interações Hospedeiro-Patógeno , Fosfoproteínas/metabolismo , Doenças das Plantas/imunologia , Triticum/metabolismo , Parede Celular/metabolismo , Eletroforese em Gel Bidimensional , Regulação da Expressão Gênica de Plantas , Fosfoproteínas/genética , Fosforilação , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Salicílico/metabolismo , Triticum/imunologia , Triticum/microbiologia
11.
Anal Methods ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973362

RESUMO

Herein, a new dual-model photoelectrochemical (PEC)/electrochemical (EC) sensor based on Z-scheme titanium dioxide (TiO2) disk/methylene blue (MB) sensibilization for the detection of kanamycin (Kana) was developed. Metal-organic framework-derived porous TiO2 disks were synthesized and exhibited excellent anodic photocurrent under visible light excitation. Subsequently, amino-labeled double-stranded DNA (dsDNA) was introduced into the modified electrode. Photocurrent was enhanced with MB embedded in dsDNA to form Z-scheme TiO2/MB sensibilization. When the target, Kana, was present, it specifically bound to the aptamer in the dsDNA, leading to the disruption of the dsDNA structure and the release of MB. This release of MB and the increase in target spatial resistance resulted in a significant weakening of PEC signal and a decreased oxidation peak current of MB. The PEC sensor successfully detected Kana in the range of 2-1000 pM with an LOD of 0.17 pM. Meanwhile, the EC sensor for Kana detection showed a linear range of 5-500 pM with an LOD of 1.8 pM. Additionally, the sensor exhibited excellent selectivity, reproducibility, stability, and good recoveries when applied to milk and honey samples. As a result, this method has the potential for application in ensuring food safety through the rapid determination of antibiotics in food.

12.
Talanta ; 273: 125878, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38492286

RESUMO

Long non-coding RNA (LncRNA) as an emerging tumor biomarker plays a key factor in the early diagnosis of cancer. Herein, an innovative signal-switchable photoelectrochemical (PEC) biosensor based on ZrO2@CuO bimetallic oxides and T7 Exo-assisted signal amplification is reported for the ultrasensitive and selective detection of lncRNA (HOX gene antisense intergenic RNA, HOTAIR) in cancer cells. Firstly, MOFs-derived TiO2 nanodisks as an excellent photoactive material show an anodic background signal. When target lncRNA exists, the abundant auxiliary DNA1 is freed from T7 Exo-assisted cycle signal amplification, and then competitively hybridizes with auxiliary DNA2 on the electrode. Subsequently, bimetallic MOFs-derived ZrO2@CuO octahedra with a high specific surface area and porous structure are introduced into TiO2 nanodisks-modified biosensor, which appears a cathodic photocurrent and achieves a switchable signal. The developed signal-switchable PEC biosensor shows ultrasensitive detection of lncRNA HOTAIR with a detection limit of 0.12 fM, and can eliminate the false interference. Importantly, the established PEC biosensor has good correlation with RT-qPCR analysis (P < 0.05) for the quantification of lncRNA HOTAIR in cancer cells, which has great potential application for biomarker detection in the early diagnosis of cancer.


Assuntos
Técnicas Biossensoriais , Neoplasias , RNA Longo não Codificante , Técnicas Eletroquímicas , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Limite de Detecção , Neoplasias/diagnóstico , Neoplasias/genética
13.
Ann Transl Med ; 11(2): 72, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36819526

RESUMO

Background: Myocardial ischemia-reperfusion is a common pathological feature of many heart and vascular diseases, but the molecular mechanism of this process is still unclear, and there is no effective way to protect cardiomyocytes. The aim of this study was to examine the effects and underlying molecular mechanisms of Lycium barbarum polysaccharide (LBP) on myocardial ischemia-reperfusion injury in cardiomyocytes. Methods: The cardiomyocyte cell line H9c2 were used to establish an in vitro hypoxia/reoxygenation (H/R) model. After treatment with LBP and/or the SIRT3 inhibitor 3-TYP, cell morphology was observed under the light microscopy. The Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect cell proliferation, and flow cytometry was performed to assess cell apoptosis. The lysine (166)-acetylation of CypD1 was determined by co-immunoprecipitation assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the lactate dehydrogenase (LDH) level in the culture medium. Na+-K+-ATPase activity, Ca2+-ATPase activity, and nitric oxide (NO) levels were measured. Results: LBP alleviated cell damage and upregulated STIR3 expression in a dose-dependent manner. Upregulated SIRT3 expression and suppressed acetylation of CypD were also observed in H/R-induced H9c2 cells treated with LBP. Indeed, LBP remarkably reversed the inhibition of proliferation and cell apoptosis in H/R-induced H9c2 cells by activating SIRT3/CypD signaling. Blockade of SIRT3 with SIRT3 inhibitor (3-TYP) inhibited the protective effect of LBP on H9c2 cells. LBP markedly alleviated the H/R-induced increase of LDH release, and the decrease of Na+-K+-ATPase activity, Ca2+-ATPase activity, and NO levels. Inhibition of SIRT3 restored the protective effects of LBP. Conclusions: LPB induced deacetylation of CypD by upregulating SIRT3, thereby protecting mitochondrial function and relieving H/R-induced injury in cardiomyocytes.

14.
Anal Chim Acta ; 1277: 341644, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37604608

RESUMO

Herein, a novel silver ion-loaded gold microemulsion assemblies (Au/Ag+ MAs) mediated multifunctional signal amplification strategy was proposed to construct a sensitive immobilization-free photoelectrochemical (PEC)/colorimetric biosensor for carcinoembryonic antigen (CEA) detection. Through the sandwiched reaction among CEA, the CEA aptamer (DNA1) loaded on the Au nanoparticles (NPs) functionalized iron oxide (Fe3O4) nanospheres and another CEA aptamer (DNA2) immobilized on Au/Ag+ MAs, a complex is formed and acquired by magnetic separation. Then, Au/Ag+ MAs of the complex are disassembled into Au NPs and Ag+ ions driven by an acetone response, and the obtained demulsification solution is transferred to the cadmium sulfide/cadmium telluride (CdS/CdTe) photoactive composites modified electrode. Based on the multiple inhibition functions (blocking effect of oleylamine; energy transfer effect of Au NPs; and electron snatching effect of Ag+), the photocurrent of the electrode decreases obviously, resulting in the ultrasensitive detection of CEA (a detection limit of 16 fg mL-1). Interestingly, the ion-exchange reactions between CdS/CdTe composites and Ag+ ions generate silver sulfide/silver telluride (Ag2S/Ag2Te) composites, and a color change of composites can be distinguished directly, leading to a quick visual detection of CEA. Compared with the traditional single-modal assay for CEA, such dual-modal PEC/colorimetric assay is a more accurate and reliable due to different mechanisms and independent signal conversion. This work will offer a new perspective for the applications of various self-assemblies in PEC bioanalysis.


Assuntos
Compostos de Cádmio , Nanopartículas Metálicas , Pontos Quânticos , Antígeno Carcinoembrionário , Colorimetria , Ouro , Prata , Telúrio
15.
Chem Biol Interact ; 370: 110305, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36529159

RESUMO

Ribavirin is a common antiviral drug, especially for patients with hepatitis C. Our recent studies demonstrated that ribavirin showed anti-tumor activity in colorectal cancer and hepatocellular carcinoma, but its effects on lung cancer remains unclear. This study aimed to evaluate the anti-tumor activity of ribavirin against lung cancer and elucidate the underlying mechanism. We established orthotopic mouse model of lung cancer (LLC and GLC-82) and employed an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics approach. We found that ribavirin significantly inhibited the proliferation and colony formation of lung cancer cells. Tumor sizes of orthotopic lung cancer in ribavirin-treated groups were also significantly lower than those in control groups. Metabolomics analysis revealed that ribavirin mainly affected 5 metabolic pathways in orthotopic lung tumor models, taurine and hypotaurine metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism, arginine biosynthesis and arachidonic acid metabolism. Furthermore, we identified 5 upregulated metabolites including ß-nicotinamide adenine dinucleotide (NAD+), nicotinamide (NAM), taurine, ornithine and citrulline, and 7 downregulated metabolites including 1-methylnicotinamide (MNAM), S-adenosyl-l-homocysteine (SAH), N1-Methyl-2-pyridone-5-carboxamide (2PY), homocysteine (Hcy), linoleic acid, arachidonic acid (AA) and argininosuccinic acid in ribavirin-treated groups. These results provide new insight into the anti-tumor mechanism of ribavirin for lung cancer.


Assuntos
Neoplasias Pulmonares , Ribavirina , Camundongos , Animais , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Ácido Araquidônico , Ácido Linoleico , Metabolômica/métodos , Neoplasias Pulmonares/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos , Niacinamida , Taurina , Biomarcadores
16.
Front Pharmacol ; 14: 1113810, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36992829

RESUMO

Objective: To investigate the effects and mechanisms of Paeoniae radix rubra-Angelicae sinensis radix (P-A) drug pair in the treatment of rheumatoid arthritis (RA). Methods: Mass spectrometry was employed to accurately characterize the main components of the P-A drug pair. Network pharmacology was used to analyze the main components and pathways of the P-A drug pair in the treatment of RA, and Discovery Studio software was used to molecularly dock the key proteins on the pathway with their corresponding compounds. The levels of serum TNF-a, IL-1ß, and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). The histopathology of the ankle joint was observed by hematoxylin-eosin (HE) staining, and the positive expression of p-PI3K, p-IKK, p-NF-κB, and p-AKT in the synovial tissue of the ankle joint was detected by immunohistochemical analysis. Finally, the expression of PI3K, IKK, and AKT and their phosphorylation levels were determined by western blot in each group of rats. Results: Network pharmacology combined with molecular docking analysis revealed that the pharmacodynamic mechanism of the P-A drug pair for the treatment of RA may be related to the contents of caffeic acid, quercetin, paeoniflorin, and baicalein in the regulation of the expression of the PI3K/AKT/NF-κB signaling pathway and the targets of PIK3CA, PIK3R1, AKT1, HSP90AA1 and IKBKB in the pathway. Compared with the model group, the P-A drug pair significantly improved the pathological changes of the synovial tissue and reduced feet swelling in RA model rats. Moreover, it regulated the levels of TNF-α, IL-1ß, and IL-6 in serum (p < 0.05). The results of the immunohistochemical analysis and western blot showed that the expression of PI3K, IKK, NF-κB, and AKT decreased after phosphorylation in the synovial tissue (p < 0.05). Conclusion: The P-A drug pair exhibited an inhibitory effect on the hyperactivation of the PI3K/AKT/NF-κB signaling pathway in the synovial membrane of RA rats. The mechanism may be related to the downregulation of the phosphorylation levels PI3K, IKK, NF-κB, and AKT, which in turn decreased inflammatory cell infiltration and synovial membrane proliferation.

17.
ACS Omega ; 8(17): 15741-15750, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37151502

RESUMO

Ochratoxin A (OTA) is a common mycotoxin, and it is a significant threat to human health throughout the food chain. In this study, a sensitive and specific fluorescent sensor based on magnetic separation technology combined with chain displacement amplification was developed for fast and easy detection of OTA in food. The designed strand displacement amplification can improve the sensitivity for the detection, and the magnetic nanomaterials can provide a large surface area, thus enhancing the capture efficiency of the target from the sample. Based on those designs, the experimental results showed that the proposed method displayed excellent performance. The linearity range was 0.5-128.0 ng/mL. The detection limit was 0.125 ng/mL; the relative standard deviations were 3.92-7.71%. Additionally, the developed method was satisfactorily applied to determine OTA in wheat, corn, and red wine samples at three spiked levels (1.0, 8.0, and 64.0 ng/mL). The recoveries ranged from 85.45 to 107.8% for wheat flour, 101.34 to 108.35% for corn flour, and 91.15 to 93.80% for red wine, respectively. Compared with high-performance liquid chromatography, the proposed method showed a lower limit of detection and equal recovery. Hence, the designed method is a potential and good detecting tool for OTA residue analysis in complex matrix samples.

19.
Methods Appl Fluoresc ; 11(3)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37015242

RESUMO

In recent years, tetracyclines (TCs) is a hot research topic. Herein, we report an interesting discovery using the complexation of oxytetracycline and metal ions. In this study, according to the properties of Fe3O4nanoparticles (Fe3O4NPs) as a nanoenzyme, it can be used to catalyze the oxidation of KI by H2O2to produceI3-,while at the same timeI3-binds to rhodamine 6G (Rh6G) to form a conjoined particle (Rh6G ∼ I3)n, leading to a decrease in the fluorescence intensity of Rh6G. However, in the presence of TCs, Fe3O4NPs have a synergistic effect with TCs, leading to enhanced catalytic activity, as well as better selectivity compared to the activity of other reducing enzymes. Consequently,the fluorescent signal based on a resonance scattering effect between Rh6G andI3-is dependent on the concentration of TCs, thus achieving highly facile and robust detection of TCs. The limits of detection (LOD) of the method were 20 nM, 10 nM and 40 nM for oxytetracycline(OTC), tetracycline(TC) and chlortetracycline(CTC), respectively. Most importantly, the method can be successfully applied to the detection of TCs in milk, eggs, and honey. The recoveries of spiked samples ranged from 83.11 to 118.95%. Thus, a stable, hands-on strategy for the detection of TCs is proposed, which has potential applications in the field of food safety and environmental protection.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Oxitetraciclina , Antibacterianos , Tetraciclina , Tetraciclinas , Fluorescência , Nanopartículas Magnéticas de Óxido de Ferro/química
20.
Lab Chip ; 23(6): 1694-1702, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36789765

RESUMO

Exosomes are seen as promising biomarkers for minimally invasive liquid biopsies and disease surveillance. However, the complexity of body fluids, inherent heterogeneity, and tiny size of exosomes impede their extraction, consequently restricting their clinical application. In this study, in order to efficiently isolate exosomes from clinical samples, an irregular serpentine channel microfluidic chip (ExoSIC) was designed to continuously separate exosomes from plasma based on a magnetic-nanowaxberry (MNWB). In the ExoSIC, irregular serpentine microchannels are utilized to increase fluid chaotic mixing, hence improving exosome capture efficiency. In comparison to commonly used spherical magnetic particles, the designed MNWB can not only enhance the capture efficiency of exosomes, but also possess a size-exclusion effect to improve exosome purity. Consequently, the ExoSIC exhibited a large yield (24 times higher than differential centrifugation), optimum purity (greater than precipitation and similar to differential centrifugation), and high specificity. Furthermore, the ExoSIC was utilized for plasma-based cancer diagnosis by multiplex monitoring of five exosomal biomarkers (exosomal concentration, EGFR, EpCAM, SAA1 and FV), and the AUC reached 0.791. This work provides a comprehensive framework for exosome-based cancer diagnostics in order to meet clinical requirements for exosome isolation and downstream analysis.


Assuntos
Exossomos , Neoplasias , Humanos , Microfluídica , Biomarcadores , Neoplasias/diagnóstico , Fenômenos Magnéticos
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