RESUMEN
Hydrogen peroxide (H2O2) has always been a topic of great interests attributed to its vital role in biological process. H2O2 is known as a major reactive oxygen species (ROS) which is involve in numerous physiological processes such as cell proliferation, signal transduction, differentiation, and even pathogenesis. A plenty of diseases development such as chronic disease, inflammatory disease, and organ dysfunction are found to be relevant to abnormality of H2O2 production. Thus, imminent and feasible strategies to modulate and detect H2O2 level in vitro and in vivo have gained great importance. To date, the boronate-based chemical structure probes have been widely used to address the problems from the above aspects because of the rearranged chemical bonding which can detect and quantify ROS including hydrogen peroxide (H2O2) and peroxynitrite (ONOO-). This present article discusses boronate-based probes based on the chemical structure difference as well as reactivities to H2O2 and ONOO-. In this review, we also focus on the application of boronate-based probes in the field of cell imaging, prodrugs nanoplatform, nanomedicines, and electrochemical biosensors for disease diagnosis and treatment. In a nutshell, we outline the recent application of boronate-based probes and represent the prospective potentiality in biomedical domain in the future.
Asunto(s)
Neoplasias , Profármacos , Humanos , Peróxido de Hidrógeno , Colorantes Fluorescentes/química , Especies Reactivas de Oxígeno , Nanomedicina , Estudios Prospectivos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológicoRESUMEN
The purpose of this study was to develop a colorimetric assay for detecting hydrogen peroxide (H2 O2 ) through a combination of using an aryl boronate (AB) derivative and gold nanoparticles (AuNPs). The unique optical property of AuNPs is applied to design a detection probe. The aggregation of AuNPs could be directly observed as a color change by the naked eye. A mannoside-boronate-sulfide (MBS) ligand was designed that contains an arylboronate (AB), a mannoside, and a thiol group. The thiol group bonds covalently with the surface of AuNPs to obtain MBS@AuNPs. The mannoside moiety recognizes concanavalin A (Conâ A), a lectin with four carbohydrate recognition sites that can specifically recognize the non-reducing end of an α-D-mannoside or α-D-glucoside structure. The AB structure on MBS first reacts with H2 O2 and then inserts an oxygen atom in the B-H bond, which triggers intramolecular electron rearrangement to cleave the covalent bond, resulting in a MBSt mixture. The MBS or MBSt is then modified to citrate-coated AuNPs (c-AuNPs) to have MBS@AuNPs or MBSt@AuNPs. When the MBS@AuNPs are incubated with Conâ A, the Conâ A recognizes multiple mannosides on the surface of the MBS@AuNPs. Subsequently, the MBS@AuNPs aggregate and the solution's color changes from red to purple, but this color change does not occur in the case of MBSt@AuNPs. The phenomenon can be observed by the naked eye.
RESUMEN
Topological insulators (TI) have extremely high potential in spintronic applications. Here, a topological insulators thin-film (TITF) spin valve with the use of the segment gate-controlled potential exhibits a huge magnetoresistance (MR) value higher than 1000% at room temperature which is more than 50 times the MR of typical topological insulators (TI) spin-valves. A high spin-polarized current is provided by the band structure generated by the tunable segment potential. The results reveal a very large resistance difference between the parallel and antiparallel configurations. The MR effect is strongly influenced by the thin-film thickness, the gate potential, the gate size, and the distribution. The proposed results will help to not only improve the room-temperature performance of the spin-valves but also enhance the applications of magnetic memories and spintronic devices.
RESUMEN
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to metastasis. Paraspeckle component 1 (PSPC1) upregulation has been identified as an HCC pro-metastatic activator associated with poor patient prognosis, but with a lack of targeting strategy. Here, we report that PSPC1, a nuclear substrate of PTK6, sequesters PTK6 in the nucleus and loses its metastasis driving capability. Conversely, PSPC1 upregulation or PSPC1-Y523F mutation promotes epithelial-mesenchymal transition, stemness, and metastasis via cytoplasmic translocation of active PTK6 and nuclear translocation of ß-catenin, which interacts with PSPC1 to augment Wnt3a autocrine signaling. The aberrant nucleocytoplasmic shuttling of active PTK6/ß-catenin is reversed by expressing the PSPC1 C-terminal interacting domain (PSPC1-CT131), thereby suppressing PSPC1/PTK6/ß-catenin-activated metastasis to prolong the survival of HCC orthotopic mice. Thus, PSPC1 is the contextual determinant of the oncogenic switch of PTK6/ß-catenin subcellular localizations, and PSPC1-CT131 functions as a dual inhibitor of PSPC1 and PTK6 with potential for improving cancer therapy.
Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas de Unión al ARN/metabolismo , beta Catenina/metabolismo , Adulto , Anciano , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Línea Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Hígado/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Masculino , Ratones , Persona de Mediana Edad , Mutación , Proteínas de Unión al ARN/genética , Transducción de Señal , Regulación hacia Arriba , Proteína Wnt3A/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto JovenRESUMEN
A detection and degradation platform was developed to optically quantify the 6-enolate, 8-keto-dG, an important tautomer of mitochondrial mutated DNA 8-oxo-dG. We first found that 6-enolate, 8-keto-dG offers particular fluorescence emission under the conditions between pH â¼ 7 and â¼11. Thus, a mitochondria-targeting photosensitizer NV-12P was prepared to offer simultaneously photoinduced electron transfer and fluorescence resonance energy transfer (FRET) with 6-enolate, 8-keto-dG. Furthermore, NV-12P can also generate a reactive oxygen species to degrade 6-enolate, 8-keto-dG under irradiation conditions. This is the first publication about optical characterization, concentration detection and photodegradation of 6-enolate, 8-keto-dG, either in biological or in vitro applications.
Asunto(s)
8-Hidroxi-2'-Desoxicoguanosina/análisis , 8-Hidroxi-2'-Desoxicoguanosina/química , ADN Mitocondrial/genética , Mutación , Fotólisis , ADN Mitocondrial/química , Electroquímica , Transferencia Resonante de Energía de Fluorescencia , Células HeLa , Humanos , Modelos Moleculares , Conformación de Ácido NucleicoRESUMEN
Transmembrane pressure across the glomerular filter barrier may underlie renal failure. However, studies of renal failure have been difficult owing to a lack of in vitro models to capture the transmembrane pressure in a controlled approach. Here we report a microfluidic platform of podocyte culture to investigate transmembrane pressure induced glomerular leakage. Podocytes, the glomerular epithelial cells essential for filtration function, were cultivated on a porous membrane supplied with transmembrane pressure ΔP. An anodic aluminum oxide membrane with collagen coating was used as the porous membrane, and the filtration function was evaluated using dextrans of different sizes. The results show that dextran in 20 kDa and 70 kDa can penetrate the podocyte membrane, whereas dextran in 500 kDa was blocked until ΔP ≥ 60 mmHg, which resembles the filtration function when ΔP was in the range of a healthy kidney (ΔP < 60 mmHg) as well as the hypertension-induced glomerular leakage (ΔP ≥ 60 mmHg). Additionally, analysis showed that synaptopodin and actin were also downregulated when ΔP > 30 mmHg, indicating that the dysfunction of renal filtration is correlated with the reduction of synaptopodin expression and disorganized actin cytoskeleton. Taking together, our microfluidic platform enables the investigation of transmembrane pressure in glomerular filter membrane, with potential implications for drug development in the future.
RESUMEN
BACKGROUND: Pericardial adipose tissue (PAT) volume is highly associated with the presence and severity of cardiometabolic diseases, but the underlying mechanism is unknown. We previously demonstrated that a high-fat diet (HFD) induced metabolic dysregulation, cardiac fibrosis and accumulation of more PAT in minipigs. This study used our obese minipig model to investigate the characteristics of PAT and omental visceral fat (VAT) induced by a HFD, and the potential link between PAT and HFD-related myocardial fibrosis. MATERIALS AND METHODS: Five-month-old Lee-Sung minipigs were made obese by feeding a HFD for 6 months. RESULTS: The HFD induced dyslipidemia, cardiac fibrosis and more fat accumulation in the visceral and pericardial depots. The HFD changes the fatty acid composition in the adipose tissue by decreasing the portion of linoleic acid in the VAT and PAT. No arachidonic acid was detected in the VAT and PAT of control pigs, whereas it existed in the same tissues of obese pigs fed the HFD. Compared with the control pigs, elevated levels of malondialdehyde and TNFα were exhibited in the plasma and PAT of obese pigs. HFD induced greater size of adipocytes in VAT and PAT. Higher levels of GH, leptin, OPG, PDGF, resistin, SAA and TGFß were observed in obese pig PAT compared to VAT. CONCLUSION: This study demonstrated the similarities and dissimilarities between PAT and VAT under HFD stimulus. In addition, this study suggested that alteration in PAT contributed to the myocardial damage.
Asunto(s)
Tejido Adiposo/fisiología , Obesidad/fisiopatología , Adipocitos/patología , Adipoquinas/metabolismo , Tejido Adiposo/patología , Animales , Composición Corporal/fisiología , Tamaño de la Célula , Dieta Alta en Grasa , Dislipidemias/etiología , Dislipidemias/patología , Dislipidemias/fisiopatología , Ácidos Grasos/química , Femenino , Fibrosis/fisiopatología , Grasa Intraabdominal/patología , Grasa Intraabdominal/fisiología , Metabolismo de los Lípidos/fisiología , Masculino , Miocardio/patología , Obesidad/patología , Estrés Oxidativo/fisiología , Pericardio/fisiología , Porcinos , Porcinos EnanosRESUMEN
A water-soluble pH sensor, 2-(6-(4-aminostyryl)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-N, N-dimethylethanamine (ADA), was synthesized based on the molecular design of photoinduced electron transfer (PET) and intramolecular charge transfer (ICT). The fluorescence emission response against a pH value is in the range 3-6, which is suitable for labelling intracellular pH-dependent microenvironments. After biological evolution, ADA is more than a pH biosensor because it is also an endocytosis pathway tracking biosensor that labels endosomes, late endosomes, and lysosome pH gradients. From this, the emissive aggregates of ADA and protonated-ADA in these organs were evaluated to explore how this probe stresses emission colour change to cause these unique cellular images.
Asunto(s)
Colorantes Fluorescentes/química , Imagen Óptica , Orgánulos/química , Células Cultivadas , Colorantes Fluorescentes/síntesis química , Humanos , Concentración de Iones de Hidrógeno , Estructura MolecularRESUMEN
Unlike traditional binary nanostructures that construct chemotherapy drugs and photodynamic therapy photosensitizers, we introduce a molecule with a chemo-photodynamic dual therapy function. A water-soluble aggregation-induced emission enhancement (AIEE) fluorogen, NV-12P, was designed and synthesized based on asymmetric 1,6-disubstituted naphthalene and can generate particular reactive oxygen species to undergo type I photodynamic therapy under irradiation. Furthermore, this compound can specifically localize in mitochondria and, after biological evaluation, can cause mitochondrial dysfunction and potent cytotoxicity to cancer cells but not normal cells. We conclude that this compound is a potential dual-toxic efficacy molecule because it exhibits selective dark cytotoxicity and efficient photodamage in cancer cells. Additionally, we also supported the optimal combinational treatment course for the best chemo-phototherapy efficacy.
Asunto(s)
Fármacos Fotosensibilizantes/química , Células HeLa , Humanos , Mitocondrias , Fotoquimioterapia , Especies Reactivas de OxígenoRESUMEN
The G-quadruplex structures in the telomere of a chromosome can not only protect the internal chromosome sequences by preventing the improper activation of DNA-damage-response pathways but also become targets for cancer treatments. In this manuscript, we wish to prove the existence of G-quadruplex structure formation, rather than G-quadruplex sequence, in chromosome of human cancer cells. Based on our studies, the fluorescent mapping of G-quadruplex structures in the chromosome is possible with the combination of G-quadruplex targeting fluorophore (BMVC, 3, 6-bis-(1-methyl-4-vinylpyridinium)-carbazole diiodide) and duplex-binding fluorophores (Hoechst or propidium iodide). By means of an applicable incubation time between cell cycle period and proper staining procedure to the chromosome, FRET (fluorescence resonance energy transfer) between G-quadruplex targeting fluorophore and duplex-binding fluorophore can increase the signal contrast of the fluorescent color and the fluorescent mapping of quadruplex structures can be easily observed using fluorescence microscopy. These observations are further supported by basic spectral analysis, titration binding assay, gel electrophoresis binding competition assay and confocal microscopy.