RESUMO
The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus (S. aureus) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTSâ¢+). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL-1. Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.
Assuntos
Toxinas Bacterianas , Técnicas Biossensoriais , Técnicas Eletroquímicas , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/análise , Estruturas Metalorgânicas/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Peroxidase/metabolismo , Peroxidase/química , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/metabolismoRESUMO
BACKGROUND: Current therapies cannot completely reverse advanced atherosclerosis. High levels of amino acids, induced by Western diet, stimulate mTORC1 (mammalian target of rapamycin complex 1)-autophagy defects in macrophages, accelerating atherosclerotic plaque progression. In addition, autophagy-lysosomal dysfunction contributes to plaque necrotic core enlargement and lipid accumulation. Therefore, it is essential to investigate the novel mechanism and molecules to reverse amino acid-mTORC1-autophagy signaling dysfunction in macrophages of patients with advanced atherosclerosis. METHODS: We observed that Gpr137b-ps (G-protein-coupled receptor 137B, pseudogene) was upregulated in advanced atherosclerotic plaques. The effect of Gpr137b-ps on the progression of atherosclerosis was studied by generating advanced plaques in ApoE-/- mice with cardiac-specific knockout of Gpr137b-ps. Bone marrow-derived macrophages and mouse mononuclear macrophage cell line RAW264.7 cells were subjected to starvation or amino acid stimulation to study amino acid-mTORC1-autophagy signaling. Using both gain- and loss-of-function approaches, we explored the mechanism of Gpr137b-ps-regulated autophagy. RESULTS: Our results demonstrated that Gpr137b-ps deficiency led to enhanced autophagy in macrophages and reduced atherosclerotic lesions, characterized by fewer necrotic cores and less lipid accumulation. Knockdown of Gpr137b-ps increased autophagy and prevented amino acid-induced mTORC1 signaling activation. As the downstream binding protein of Gpr137b-ps, HSC70 (heat shock cognate 70) rescued the impaired autophagy induced by Gpr137b-ps. Furthermore, Gpr137b-ps interfered with the HSC70 binding to G3BP (Ras GTPase-activating protein-binding protein), which tethers the TSC (tuberous sclerosis complex) complex to lysosomes and suppresses mTORC1 signaling. In addition to verifying that the NTF2 (nuclear transport factor 2) domain of G3BP binds to HSC70 by in vitro protein synthesis, we further demonstrated that HSC70 binds to the NTF2 domain of G3BP through its W90-F92 motif by using computational modeling. CONCLUSIONS: These findings reveal that Gpr137b-ps plays an essential role in the regulation of macrophage autophagy, which is crucial for the progression of advanced atherosclerosis. Gpr137b-ps impairs the interaction of HSC70 with G3BP to regulate amino acid-mTORC1-autophagy signaling, and these results provide a new potential therapeutic direction for the treatment of advanced atherosclerosis.
Assuntos
Aterosclerose , Placa Aterosclerótica , RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/metabolismo , Aterosclerose/patologia , Placa Aterosclerótica/patologia , Macrófagos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Autofagia/fisiologia , Aminoácidos/metabolismo , Lipídeos , Mamíferos/genéticaRESUMO
Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of immune cells in the intima of arteries. Experimental and clinical evidence shows that both innate and adaptive immunity orchestrate the progression of atherosclerosis. The heterogeneous nature of immune cells within atherosclerosis lesions is important. Studies utilizing high-dimensional mass spectrometry and single-cell RNA sequencing of leukocytes from atherosclerotic lesions show the diversity and adaptability of these immune cell subtypes. Their migration, compositional changes, phenotypic alterations, and adaptive responses are key features throughout atherosclerosis progression. Understanding how these immune cells and their subtypes affect atherogenesis would help to develop novel therapeutic approaches that control atherosclerosis progression. Precise targeting of specific immune system components involved in atherosclerosis, rather than broad suppression of the immune system with anti-inflammatory agents, can more accurately regulate the progress of atherosclerosis with fewer side effects. In this review, we cover the most recent advances in the field of atherosclerosis to understand the role of various immune cells on its development. We focus on the complex network of immune cells and the interaction between the innate immune system and adaptive immune system.
Assuntos
Imunidade Adaptativa , Aterosclerose , Imunidade Inata , Humanos , Aterosclerose/imunologia , Animais , Progressão da DoençaRESUMO
AIMS: Blood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis. METHODS AND RESULTS: Immunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4-/-, and Il13-/- mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-ß receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries. CONCLUSION: Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.
Assuntos
Aterosclerose , Calcificação Vascular , Masculino , Humanos , Animais , Camundongos , Eosinófilos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas Sanguíneas/análise , Osteogênese , Receptores de Proteínas Morfogenéticas Ósseas/metabolismo , Interleucina-13/metabolismo , Proteínas Granulares de Eosinófilos/metabolismo , Ribonucleases/metabolismo , Aterosclerose/metabolismo , Camundongos KnockoutRESUMO
Enantioselective identification of chiral molecules is of paramount importance in medical science, biochemistry, and pharmaceutics owing to the configuration-dependent activities of enantiomers. However, the identical physicochemical properties of enantiomers remain challenging in chiral sensing. In this study, inspired by the peroxidase-mimicking activity of Fe(III)-based nanomaterials, an enantioselective artificial architecture is constructed on TiO2 nanochannels. Homochiral Ti-based metal-organic frameworks (MOFs) use a 2,2'-bipyridine-5,5'-dicarboxylic acid ligand as the artificial enzyme skeleton, Fe(III) as peroxidase-mimicking centers, and l-tartaric acid (TA) as a chiral recognition selector. Using l-/d-cystine as model enantiomers, the chiral moieties of l-TA on Ti-MOFs allow stereoselective recognition of guest molecules through hydrogen bonds formed between chiral cystine and the host. In a tris(2-carboxyethyl)phosphine hydrochloride-containing environment, the disulfide bonds in cystine molecules are further cleaved, and the HS-tails react with Fe(III) active sites, causing the loss of peroxidase-like performance of nanochannels. Benefitting from the nanochannel architecture's current-potential (I-V) properties, the selective recognition of cystine enantiomers is directly monitored through the peroxidase-like activity change-induced ionic current signatures. This study provides a new and universal strategy for distinguishing disulfide- and thiol-containing chiral molecules.
Assuntos
Estruturas Metalorgânicas , Nanoestruturas , Cistina , Estereoisomerismo , Depressão , Compostos FérricosRESUMO
Chiral recognition is a crucial issue in the biomedical and pharmaceutical research communities. Due to the need for expensive equipment, reagents, and external energy, enantiomer identification is difficult to perform outside of a laboratory. Based on water evaporation-induced hydrovoltaic effect, a power-free sensing platform with sensitive chiral recognition capability is proposed for the discrimination of enantiomers. The chiral recognizer was bovine serum albumin (BSA), a naturally occurring protein. Using arginine (Arg) enantiomers as the sensing targets, the difference in enantioselectivity between l-Arg and d-Arg on a BSA-modified porous carbon substrate can be measured directly from the output voltage. By combining the cyclization reaction between NO and O-phenylenediamine (OPD), it has been discovered that the sensitivity and specificity of enantioselective identification can be significantly enhanced based on the surface charges. The limit of detection (LOD) could be as low as 76.0 nM. In addition, the proposed chips are extremely flexible and can function under deformation without sacrificing output performance. This self-powered chiral recognition chip paves a new path for the detection of chiral molecules at any time, any place, and it also has excellent potential for use in flexible wearable technology.
Assuntos
Arginina , Dispositivos Eletrônicos Vestíveis , Arginina/química , Estereoisomerismo , Água , Soroalbumina BovinaRESUMO
Enantioselective identification of chiral molecules is regarded as one of the key issues in biological and medical sciences because of their configuration-dependent effects on biological systems. In this study, we developed an electrochemical platform based on a tandem recognition-reaction zone design in TiO2 nanochannels for the specific recognition of reducing enantiomers. In this system, MIL-125(Ti) Ti-metal-organic frameworks, in situ grown in TiO2 nanochannels, provided a homochiral recognition environment via postmodification with l-tartaric acid (l-TA); MnO2 nanosheets possessing both glucose oxidase (GOD)- and peroxidase (POD)-mimicking activities served as the target-reactive zone at the end of the nanochannels. The use of penicillamine (Pen) enantiomers as model-reducing targets facilitated the passage of d-Pen through the homochiral recognition zone, owing to its lower affinity with l-TA. The passed Pen molecules reached the responsive zone and induced a target concentration-dependent MnO2 disassembly. Such target recognition event impaired the cascade GOD- and POD-like activities of MnO2. Combining the enantioselectivity of the recognition nanochannels with the cascade enzyme-like activity of MnO2 toward glucose and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate), the quantitative identification of l- and d-Pen was achieved through the changes in transmembrane ionic current induced by the generated charged products. This recognition-reaction zone design paves an effective way for developing a promising electrochemical platform for the identification of reducing enantiomers with improved selectivity and sensitivity.
Assuntos
Compostos de Manganês , Óxidos , Estereoisomerismo , Glucose Oxidase , PenicilaminaRESUMO
Enzyme-mimicking nanoparticles play a key role in important catalytic processes, from biosensing to energy conversion. Therefore, understanding and tuning their performance is crucial for making further progress in biological applications. We developed an efficient and sensitive electrochemical method for the real-time monitoring of the glucose oxidase (GOD)-like activity of single nanoparticle through collision events. Using brush-like sulfonate (-SO3-)-doped polyaniline (PANI) decorated on TiO2 nanotube arrays (TiNTs-SPANI) as the electrode, we fabricated a proton reservoir with excellent response and high proton-storage capacity for evaluating the oxidase-like activity of individual Au nanoparticles (AuNPs) via instantaneous collision processes. Using glucose electrocatalysis as a model reaction system, the GOD-like activity of individual AuNPs could be directly monitored via electrochemical tests through the nanoparticle collision-induced proton generation. Furthermore, based on the perturbation of the electrical double layer of SPANI induced by proton injection, we investigated the relationship between the measured GOD-like activities of the plasmonic nanoparticles (NPs) and the localized surface plasmon resonance (LSPR) as well as the environment temperature. This work introduces an efficient platform for understanding and characterizing the catalytic activities of nanozymes at the single-nanoparticle level.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Oxirredutases , Ouro/química , Técnicas Biossensoriais/métodos , Prótons , Nanopartículas Metálicas/química , Glucose Oxidase/químicaRESUMO
Glutathione (GSH) plays a vital role in many physiological processes, and its abnormal levels have been found to be associated with several diseases. In contrast to traditional methods using electron donor-containing electrolytes for photoelectrochemical (PEC) sensing, in this study, a target-driven electron donor generation in a PEC electrode was developed to detect GSH. Using well-aligned TiO2 nanotube arrays (TNTs) as the PEC substrate, mesoporous MIL-125(Ti) was grown in the TNTs through an in situ solvothermal method and subsequent two-step annealing treatment. The accommodation capacity of mesoporous MIL-125(Ti) allows a well loading of cystine and Pt nanoclusters (NCs). Taking advantage of the specific cleavage ability of disulfide bonds by GSH, cystine was converted to cysteine, which served as the electron donor for the PEC process. Benefiting from the confinement effect of mesoporous MIL-125(Ti), cysteine was effectively oxidized to cysteine sulfinic acid by the photogenerated holes. Importantly, the highly active Pt NCs decorated in the mesopores not only improved the charge transfer but also accelerated the above oxidation reaction. The synergistic effect of these factors enabled the efficient separation of the photogenerated electron-hole pairs, which induced a significant photocurrent increase and in turn led to the high-sensitivity detection of GSH. Consequently, the proposed PEC biosensor exhibited excellent performance in the detection of GSH in serum specimens. The target-driven electron donor generation designed in this study might open a new route for developing sensitive and selective PEC biosensors with application in complex biological environments.
Assuntos
Cisteína , Cistina , Elétrons , Eletrodos , GlutationaRESUMO
Accurate detection of trace biomarkers in biological samples is a key task in diagnostic testing, but it remains challenging due to the high concentration of other physiologically relevant interferences. This work presents a new electrochemiluminescence (ECL) sensing device based on a bio-inspired nanochannel membrane (NM) guarded with two differential gates. The recognition event at the aptamer gate is followed by the permitting of stimulator transport toward the metal-organic framework (MOF) gate. Proof of concept application is evaluated using cytochrome C (Cytc) as the analyte, and glucose, a commonly existing nutriment as the stimulator. The oxidase-mimic plasmonic nanoparticles induce an effective release of ECL luminophore from the MOF gate. This cascade-gates guarded NM can effectively separate biological matrices from the detection cell. Consequently, the proposed system can achieve direct sensing of 1.0 nm Cytc in undiluted serum within the threshold concentrations of leukemia and lymphoma, making it attractive for point-of-care applications.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , Nanopartículas , Medições Luminescentes , Biomarcadores , Técnicas Eletroquímicas , Limite de DetecçãoRESUMO
RATIONALE: Blood eosinophil count and ECP (eosinophil cationic protein) associate with human cardiovascular diseases. Yet, whether eosinophils play a role in cardiovascular disease remains untested. The current study detected eosinophil accumulation in human and murine abdominal aortic aneurysm (AAA) lesions, suggesting eosinophil participation in this aortic disease. OBJECTIVE: To test whether and how eosinophils affect AAA growth. METHODS AND RESULTS: Population-based randomized clinically controlled screening trials revealed higher blood eosinophil count in 579 male patients with AAA than in 5063 non-AAA control (0.236±0.182 versus 0.211±0.154, 109/L, P<0.001). Univariate (odds ratio, 1.381, P<0.001) and multivariate (odds ratio, 1.237, P=0.031) logistic regression analyses indicated that increased blood eosinophil count in patients with AAA served as an independent risk factor of human AAA. Immunostaining and immunoblot analyses detected eosinophil accumulation and eosinophil cationic protein expression in human and murine AAA lesions. Results showed that eosinophil deficiency exacerbated AAA growth with increased lesion inflammatory cell contents, matrix-degrading protease activity, angiogenesis, cell proliferation and apoptosis, and smooth muscle cell loss using angiotensin-II perfusion-induced AAA in Apoe-/- and eosinophil-deficient Apoe-/-ΔdblGATA mice. Eosinophil deficiency increased lesion chemokine expression, muted lesion expression of IL (interleukin) 4 and eosinophil-associated-ribonuclease-1 (mEar1 [mouse EOS-associated-ribonuclease-1], human ECP homolog), and slanted M1 macrophage polarization. In cultured macrophages and monocytes, eosinophil-derived IL4 and mEar1 polarized M2 macrophages, suppressed CD11b+Ly6Chi monocytes, and increased CD11b+Ly6Clo monocytes. mEar1 treatment or adoptive transfer of eosinophil from wild-type and Il13-/- mice, but not eosinophil from Il4-/- mice, blocked AAA growth in Apoe-/-ΔdblGATA mice. Immunofluorescent staining and immunoblot analyses demonstrated a role for eosinophil IL4 and mEar1 in blocking NF-κB (nuclear factor-κB) activation in macrophages, smooth muscle cells, and endothelial cells. CONCLUSIONS: Eosinophils play a protective role in AAA by releasing IL4 and cationic proteins such as mEar1 to regulate macrophage and monocyte polarization and to block NF-κB activation in aortic inflammatory and vascular cells.
Assuntos
Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/prevenção & controle , Eosinófilos/metabolismo , Remodelação Vascular , Transferência Adotiva , Idoso , Angiotensina II , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Células Cultivadas , Dilatação Patológica , Modelos Animais de Doenças , Eosinófilos/transplante , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Monócitos/metabolismo , NF-kappa B/metabolismo , Fenótipo , Ribonucleases/metabolismoRESUMO
The space-agile optical composite detection (SOCD) system with a pointing mirror possesses flexible and fast response ability. Like other space telescopes, if the stray light is not properly eliminated, it may result in a false response or noise that floods the real light signal due to the low illuminance and large dynamic range of the target. The paper shows the optical structure layout, the decomposition of the optical processing index and roughness control index, the stray light suppression requirements, and the detailed stray light analysis process. The pointing mirror and ultra-long afocal optical path increase the difficulty of stray light suppression in the SOCD system. This paper presents the design method of a special-shaped aperture diaphragm and entrance baffle, black baffle surface testing, simulating, selection, and stray light suppression analysis process. The special-shaped entrance baffle has a significant effect on the suppression of stray light and reduced dependence on the platform posture of the SOCD system.
RESUMO
In recent years, an increasing number of scientists have focused on conducting experiments on laser ablation of bone tissue. The purpose of this study was to summarize the prognosis of tissue and the extent of thermal damage in past hard tissue ablation experiments, and review the evidence for the feasibility of laser osteotomy in surgery. An electronic search of PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science (WOS) for relevant English-language articles published through June 2023 was conducted. This review includes 48 literature reports on laser ablation of hard tissues from medical and biological perspectives. It summarizes previous studies in which the ideal ablation rate, depth of ablation, and minimal damage to bone tissue and surrounding soft tissues were achieved by changing the laser type, optimizing the laser parameter settings, or adding adjuvant devices. By observing their post-operative healing and inflammatory response, this review aims to provide a better understanding of pulsed laser ablation of hard tissues. Previous studies suggest that laser osteotomy has yielded encouraging results in bone resection procedures. We believe that low or even no thermal damage can be achieved by experimentally selecting a suitable laser type, optimizing laser parameters such as pulse duration and frequency, or adding additional auxiliary cooling devices. However, the lack of clinical studies makes it difficult to conclusively determine whether laser osteotomy is superior in clinical applications.
Assuntos
Terapia a Laser , Prognóstico , Terapia a Laser/efeitos adversos , Osso e Ossos , Osteotomia , ChinaRESUMO
It is important to detect cancer biomarkers at an early stage of tumor development for the effective diagnosis and treatment of cancer. As a well-known probe for detecting superoxide (·O2-) radicals, nitro blue tetrazolium (NBT) can rapidly react with ·O2- to form a hydrophobic formazan precipitate. In this study, by deliberately utilizing this reaction, Pt asymmetrically decorated on a TiO2 nanochannel membrane (Pt/TiNM) is explored to fabricate an electrochemical immunosensing platform with outstanding selectivity and ultrahigh sensitivity. Using NBT as the substrate, hydrophobic formazan precipitation induces a substantial block of ionic diffusion flux in nanochannels. Using alpha fetoprotein (AFP) as the target analyte, the established immunorecognition event was used to induce MoS2-Ab2 conjugates. Thanks to the excellent light-shielding ability of MoS2 nanosheets, the production of ·O2- radicals from the photocatalysis of Pt/TiNM is effectively depressed because of the attenuated arrival of light. The reduced formazan precipitation results in ionic transport changes in nanochannels, which in turn enables the selective recognition of AFP down to 2 ng mL-1. This target-modulated sensing strategy is also capable of sensing other immune targets, thus paving a new way for designing nanochannel-based sensing platforms.
Assuntos
Técnicas Biossensoriais , alfa-Fetoproteínas , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Formazans , Molibdênio , Nitroazul de TetrazólioRESUMO
Chiral enantiomers have different effects on biological processes. Enantiomer separation is significant and necessary. Herein, a photothermal (PT) effect-derived enantioselective desorption strategy based on homochiral Au/TiO2 nanotubes (NTs) is developed. Using 3,4-dihydroxyphenylalanine (DOPA) as the model enantiomer, an obvious selective desorption of L/D-DOPA can be achieved by the NIR light-triggered local temperature enhancement. Molecular docking simulation further verifies that the distinct affinity precipitated by the different hydrogen bonds between homochiral sorbent and target enantiomers is the origin of enantioselective desorption. This desorption strategy provides a green and alternative approach for the selective separation of chiral molecules.
Assuntos
Nanotubos , Simulação de Acoplamento Molecular , Estereoisomerismo , Titânio/químicaRESUMO
BACKGROUND: Recent study has shown that the transient receptor potential vanilloid 2 (TRPV2) channel was exclusively upregulated in patients with atrial fibrillation (AF), and that this overexpression might be detrimental for occurrence and maintenance of AF. We aimed to characterize the expression levels of TRPV2 mRNA in peripheral blood mononuclear cells (PBMCs) with/without early recurrence of atrial fibrillation (ERAF) after radiofrequency catheter ablation (RFCA), and to find a reliable predictor for ERAF. METHODS: 65 patients of AF, who underwent RFCA successfully, then divided into two groups according to ERAF during following 3 months. PBMCs were isolated from whole blood by Ficoll gradient centrifugation before and after RFCA. Gene set enrichment analysis was performed to evaluate TRPV channels expression levels and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping was used for pathway enrichment analysis. RESULTS: There was no significant difference in the TRPV2 mRNA expression level between the two groups before RFCA, while without ERAF group of TRPV2 expression was markedly reduced compared to ERAF group after RFCA. Moreover, the number of TRPV2 expression was confirmed as an independent predictor for the first time through receiver operating characteristic and Kaplan-Meier survival curve analysis. It should be pointed out that the above results were only used to predict ERAF, and have no predictive significance for late recurrence of atrial fibrillation according to the current data. Additionally, ERAF was inversely correlated with P wave dispersion. KEGG mapping further clustered 41 pathways, revealing that ''cyclic guanosine monophosphate-protein kinase G signaling pathway'' was significantly enriched. CONCLUSIONS: We firstly assume that downregulated expression of peripheral TRPV2 appear in patients without ERAF after RFCA. TRPV2 may thus represent a novel predictor of early phase after successful radiofrequency ablation.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/genética , Fibrilação Atrial/cirurgia , Leucócitos Mononucleares , Recidiva , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , RNA Mensageiro/genética , Canais de Cátion TRPV/genéticaRESUMO
Imidazole and tetrazole derivatives are widely used as clinical drugs since they possess a variety of pharmaceutical function. Zinc and iron are essential trace elements of the human body, with less toxicity and good biocompatibility. In this paper, two new essential metal mononuclear complexes [M(H2tmidc)2(H2O)2]·2H2O (M = Zn (1), Fe (2)) were synthesized through the reaction of 2-((1H-tetrazol-1-yl)methylene)-1H-imidazole-4,5-dicarboxylic acid (H3tmidc) and ZnSO4·7H2O or FeSO4·7H2O. The crystal structures were determined by means of the X-ray single crystal diffraction technique. Results from fluorescence investigations show that both complexes could interact with BSA as well as HSA through the static quenching mechanism. van der Waals forces and hydrogen bonds play important roles in the interaction of complexes and BSA/HSA since both ΔH and ΔS values are negative. The results of molecular docking are consistent with those in experimental studies. Furthermore, the anticancer activity of H3tmidc and both complexes against Eca-109 were preliminarily evaluated and the results show that both complexes have better anticancer activity than the corresponding ligand H3tmidc.
Assuntos
Complexos de Coordenação , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Humanos , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , TermodinâmicaRESUMO
Enantioselective identification of chiral molecules is important for biomedical and pharmaceutical research. However, owing to identical molecular formulas and chemical properties of enantiomers, signal transduction and amplification are still the two major challenges in chiral sensing. In this study, we developed an enantioselective membrane by integrating homochiral metal-organic frameworks (MOFs) with nanochannels for the sensitive identification and quantification of chiral compounds. The membrane was designed using a TiO2 nanochannel membrane (TiNM) as the metal ion precursor of MOFs (using MIL-125(Ti)) and incorporating l-glutamine (l-Glu) into the framework of MIL-125(Ti). Using 3,4-dihydroxyphenylalanine (DOPA) as the model analyte, the as-prepared homochiral l-Glu/MIL-125(Ti)/TiNM exhibits a remarkable chiral recognition to d-DOPA than l-DOPA. More importantly, benefiting from the highly enlarged surface area and confinement effect provided by the MOFs-in-nanochannel architecture, the discrimination for chiral recognition is largely amplified through the chelation interaction of Fenton-like activity of Fe3+ onto DOPA. Using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) as the substrate, the positively charged ABTSâ¢+ product via Fenton-like reaction induces significant ionic transport changes in nanochannels, which in turn provides information about chiral recognition. This innovative signal amplification strategy on homochiral nanochannels might pave a new way for sensitive monitoring and chiral recognition.
Assuntos
Estruturas Metalorgânicas , Di-Hidroxifenilalanina , Estereoisomerismo , TitânioRESUMO
The high cost and easy denaturation of natural enzymes under environmental conditions hinder their practical usefulness in sensing devices. In this study, peroxidase (POD)-like metal-organic frameworks (MOFs) were in situ grown in the nanochannels of an anodized TiO2 membrane (TiO2NM) as an electrochemical platform for multitarget sensing. By directly using a nanochannel wall as the precursor of metal nodes, Ti-MOFs were in situ derived on the nanochannel wall. Benefitting from the presence of bipyridine groups on the ligands, the MOFs in the nanochannels provide plenty of sites for Fe3+ anchoring, thus endowing the resulting membrane (named as Fe3+:MOFs/TiO2NM) with remarkable POD-like activity. Such Fe3+-induced POD-like activity is very sensitive to thiol-containing molecules owing to the strong coordination effect of thiols on Fe3+. Most importantly, the POD-like activity of nanochannels can be in situ characterized by the current-potential (I-V) properties via catalyzing the oxidation of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) substrate to the corresponding positively charged product ABTSâ¢+. As a proof-of-concept application, the free-standing POD-like membranes were applied as a label-free assay in sensing cysteine, as well as monitoring acetylcholinesterase (AChE) activity through the generated thiol-containing product. Furthermore, based on the toxicity effect of organophosphorus (OP) compounds on AChE, the robust membranes were successfully utilized to evaluate the toxicity of diverse OP compounds. The POD-like nanochannels open up an innovative way to expand the application of nanochannel-based electrochemical sensing platforms in drug inspection, food safety, and environmental pollution.
Assuntos
Estruturas Metalorgânicas , Oxirredução , Peroxidase , TitânioRESUMO
Enantioselective sensing of chiral molecules is an important issue for both biomedical research and the pharmaceutical industry. Here, an enantioselective photoelectrochemical (PEC) sensor was constructed by integrating TiO2 nanotubes (NTs) with metal-organic frameworks (MOFs) for the identification of enantiomers. TiO2 NTs prepared by electrochemical anodization can not only be used as the PEC platform but also as the metal-ion precursor to react with terephthalic acid (BDC) to form MIL-125(Ti) in situ. A postsynthetic exchange (PSE) method was used for exchanging the ligand of MIL-125 by 2-aminoterephthalic acid (BDC-NH2) for further functionalization. Homochirality was then successfully introduced into achiral MIL-125-NH2 by postsynthetic modification (PSM) with l-histidine (l-His). The resulting homochiral metal-organic frameworks (MOF)-in-NT architecture exhibits excellent discrimination ability for the chiral recognition of 3,4-dihydroxyphenylalanine (l/d-DOPA) enantiomers. Moreover, by adjusting the charge-carrier separation-induced photocurrent variation mechanism, the as-proposed homochiral PEC electrode exhibits a broad application potential for the discrimination of enantiomers. Because of the construction of binder-free monochiral MOF-in-NT structure directly on a Ti-metal substrate, the valuable feature is that the PEC sensing platform can be used directly, thereby providing a stable, simplified, and low-cost sensing device for the recognition of chiral enantiomers.