RESUMEN
Emodin is an important anthraquinone compound with good anti-inflammatory activity in Chinese traditional medicine rhubarb. Detailed spatial distribution information in bio-tissues plays an important role in revealing the pharmacodynamics, toxicology and chemical mechanism of emodin. Herein, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) analytical method was established to obtain information on the spatial and temporal changes of emodin in multiple mouse tissue sections (heart, liver, spleen, lung, kidney, and brain) after intraperitoneal injection of emodin in mice. The measurements were accomplished in the negative ion mode in the range of m/z 250-285 Da with a spatial resolution on 40 µm. It was found that emodin was predominantly distributed in the arteriolar vascular region of the heart, the capsule region of the spleen, and the cortex of the kidney. Moreover, the MALDI-TOF-MSI result implied that emodin might be distributed in the brain. These more detailed spatial distribution information provides the significant reference for investigating the action mechanism of emodin, which cannot be obtained from conventional LC-MS analysis. The distribution trend of emodin in the results of MALDI-TOF-MSI analysis agreed with the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) results well, demonstrating the complementarity and reliability of the established MALDI-TOF-MSI method. Our work provided a label-free molecular imaging method to investigate the precise spatial distribution of emodin in various organs, which prove great potential in studying the effective substances and mechanism of rhubarb.
RESUMEN
ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.
Asunto(s)
Neoplasias de la Mama , Quempferoles , Nanopartículas , Silicio , beta-Galactosidasa , Femenino , Humanos , beta-Galactosidasa/metabolismo , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Colorimetría , Quempferoles/química , Quempferoles/farmacología , Células MCF-7 , Estructura Molecular , Nanopartículas/química , Tamaño de la Partícula , Silicio/químicaRESUMEN
Residues of endocrine disrupting steroid hormones in food might cause various diseases like cardiovascular diseases and breast and prostate cancers. Monitoring steroid hormone levels plays a vital role in ensuring food safety and exploring the pathogenic mechanism of steroid hormone-related diseases. Based on the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction, a novel chemoselective probe, Azo-N3, which contains a reactive site N3, an imidazolium salt-based MS tag, and an azobenzene-based photoswitchable handle, was designed and synthesized to label ethynyl-bearing steroid hormones. The probe Azo-N3 was applied for the highly selective and sensitive detection of four ethynyl-bearing steroid hormones in food samples (milk, egg, and pork) by using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The ionization efficiency of the labeled analytes could be increased by 6-105-fold, and such a labeled method exhibited satisfactory detection limits (0.04-0.2 µg/L), recovery (80.6-122.4%), and precision (RSDs% lower than 6.9%). Interestingly, the efficient immobilization of the probe Azo-N3 onto α-cyclodextrin (α-CD)-modified magnetic particles to construct a solid supported chemoselective probe Fe3O4-CD-Azo-N3 and UV light-controlled release of the labeled analytes from a magnetic support can be achieved by taking advantage of the photoswitched host-guest inclusion between the azobenzene unit and α-CD. The potential applications of Fe3O4-CD-Azo-N3 for labeling, capturing, and the photocontrolled release of the labeled steroid hormones were fully investigated by mass spectrometry imaging analysis. This work not only provides a sensitive and accurate method to detect steroid hormones in food but also opens a new avenue in designing solid supported chemoselective probes.
Asunto(s)
Hormonas , Espectrometría de Masas en Tándem , Humanos , Masculino , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Esteroides/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
ß-Glucosidase (ß-Gluco) is an enzyme that is crucial to numerous diseases, including cancer, and in sector of industries, it is used in the manufacturing of food. Measuring its enzymatic activity is critical for biomedical studies and other activities. Herein, we have developed a novel and precise fluorescent sensing method for measuring ß-Gluco activity based on the production of yellow-green fluorescent quercetin-silicon nanoparticles (Q-SiNPs) produced from quercetin (QN) as a reducing agent and 3-[2-(2-aminoethyl amino) ethylamino] propyl-trimethoxy silane (AEEA) as a silane molecule. ß-Gluco hydrolyzed quercetin-3-O-ß-d-glucopyranoside (QO-ß-DG) to produce QN, which was then used to produce Q-SiNPs. Reaction parameters, including temperature, time, buffer, pH, and probe concentration, were carefully tuned in this study. Subsequently, the fluorescence intensity was performed, showing good linearity (R2 = 0.989), a broad linear dynamic range between 0.5 and 12 U L-1, and a limit of detection (LOD) as low as 0.428 U L-1, which was proven by fluorescence measurements. Most importantly, various parameters were detected and characterized with or without ß-Gluco. The designed probe was successively used to assess ß-Gluco activity in human serum and moldy bread. However, the mathematical findings revealed recoveries for human serum ranging from 99.3 to 101.66% and for moldy bread from 100.11 to 102.5%. Additionally, Q-SiNPs were well suited to being incubated in vitro with L929 and SiHa living cells, and after using an Olympus microscope, imaging showed good fluorescence cell images, and their viability evinced minimal cytotoxicity of 77% for L929 and 88% for SiHa. The developed fluorescence biosensor showed promise for general use in diagnostic tests. Therefore, due to this outstanding sensing modality, we anticipate that this research can provide a novel schematic project for creating simple nanostructures with a suitable plan and a green synthetic option for enzyme activity and cell imaging.
Asunto(s)
Celulasas , Nanopartículas , Humanos , Quercetina , Silicio/química , Silanos , Nanopartículas/química , Colorantes Fluorescentes/químicaRESUMEN
Herein, we developed a class of functionalized silicon nanoparticles (F-SiNPs) bio-probes named thiol-conjugated F-SiNPs. They combine excellent biocompatibility with small dimensions (<10 nm) and biological usefulness with sustained and robust fluorescence (3.32% photoluminescent quantum yield). Identifying 3-Mercaptopropionic acid (3-MPA), which lowers the quantity of gamma-aminobutyric acid in the brain, and mercury (Hg2+) was a crucially important step since their excessive levels are a sign of several disorders. Using F-SiNPs as a fluorescent bio-probe, we provided an "off-on" technique for sensitively and selectively determining Hg2+ and 3-MPA in this study. The 3-(2-aminoethylamino) propyl (dimethoxymethylsilane) and basic fuchsin as precursors were hydrothermally treated to produce the F-SiNPs exhibiting green fluorescence. Our results suggest that Hg2+ reduced the fluorescence of F-SiNPs because of strong ionic interactions and metal-ligand binding among many thiols and carboxyl groupings at the surface of Hg2+ and F-SiNPs. Additionally, the resultants demonstrated that after being quenched by Hg2+, the produced F-SiNPs led to the distinctive "off-on" response to 3-MPA. Moreover, the method could detect Hg2+ and 3-MPA with limits of detection of 0.065 µM and 0.017 µM, respectively. The technique employed is quick, easy, affordable, and environmentally friendly. The sensing platform has successfully determined Hg2+ and 3-MPA in urine, water, and human serum samples.
Asunto(s)
Mercurio , Nanopartículas , Humanos , Silicio , Ácido 3-Mercaptopropiónico , Colorantes Fluorescentes , Espectrometría de Fluorescencia/métodos , Compuestos de SulfhidriloRESUMEN
Hydroxyapatite (HA) bioceramic coating has been extensively applied for the modification of metallic implants to improve their biocompatibility and service life after implantation. Unfortunately, HA coating often suffers from high friction, severe wear, and bacterial invasion, which restrict its application in artificial joints. According to a bioinspired soft/hard combination strategy, a novel HA composite coating that is infiltrated with a vancomycin-loaded graphene oxide (GO) hybrid supramolecular hydrogel is developed via vacuum infiltration and a subsequent host-guest interaction-induced self-assembly process. The holes of textured HA ceramic coating act just like a "magic pocket", offering a stable container to form and store GO hybrid hydrogels and even to recycle wear debris as well. The drug-loaded hybrid hydrogels stored in textured HA coating possess a unique shear force and/or frictional heat triggered gel-sol transition and sustained drug release behavior, acting like the extrusion of synovial fluid during articular cartilage movement, leading to a remarkable self-lubrication, anti-wear performance, and promising antibacterial property against Staphylococcus aureus. The friction coefficient and wear rate of composite coating reduced by nearly five times and three orders of magnitude compared with textured HA coating, respectively, which benefited from the synergistic lubricate effect of cyclodextrin-based pseudopolyrotaxane supramolecular hydrogel and GO lubricants.
Asunto(s)
Grafito , Hidrogeles , Antibacterianos/farmacología , Durapatita/farmacología , Grafito/farmacología , Hidrogeles/farmacologíaRESUMEN
Inspired by the structure and dynamic weeping lubricating mechanism of articular cartilage, a novel composite coating composed of a textured Y2O3-stabilized ZrO2 (YSZ) ceramics reservoir and silver nanoparticles (AgNPs) hybrid supramolecular hydrogel was developed on the basis of a soft/hard combination strategy. The precursor solution including the poly(ethylene glycol) (PEG)-modified AgNPs and α-cyclodextrins (α-CDs) could be infiltrated deep into (50-60 µm) the pores of a textured YSZ ceramics substrate by a vacuum infiltration method, in situ forming a supramolecular hydrogel within the pores through host-guest inclusion between α-CDs and PEG chains distributed onto the surface of AgNPs. The AgNPs hybrid hydrogel showed thixotropic and thermoresponsive gel-sol transition behavior, low cytotoxicity, and excellent drug-loading capacity, as well as significant antibacterial properties. The textured YSZ ceramics not only provided a hard supporting skeleton and stable reservoir to protect the supramolecular hydrogel from destruction under load-bearing or shear condition, but also allowed retaining the stimuli-responsive gel-sol transition property and drug-release capability of the infiltrated hydrogel, endowing the composite coating with excellent antibacterial properties, and self-lubrication and wear-resistance performance. The composite coating in this work brings a new insight into the design of antibacterial and self-lubricating ceramic coatings for artificial joint applications.
Asunto(s)
Antibacterianos/farmacología , Cerámica/farmacología , Escherichia coli/efectos de los fármacos , Hidrogeles/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Cerámica/síntesis química , Cerámica/química , Hidrogeles/síntesis química , Hidrogeles/química , Sustancias Macromoleculares/síntesis química , Sustancias Macromoleculares/química , Sustancias Macromoleculares/farmacología , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Tamaño de la PartículaRESUMEN
Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.