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1.
Small ; 20(26): e2309035, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38234137

RESUMEN

Lanthanide-doped upconversion nanoparticles (UCNPs) hold promise for single-molecule imaging owing to their excellent photostability and minimal autofluorescence. However, their limited water dispersibility, often from the hydrophobic oleic acid ligand during synthesis, is a challenge. To address this, various surface modification strategies' impact on single-particle upconversion luminescence are studied. UCNPs are made hydrophilic through methods like ligand exchange with dye IR806, HCl or NOBF4 treatment, silica coating (SiO2 or mesoporous mSiO2), and self-assembly with polymer of DSPE-PEG or F127. The studies revealed that UCNPs modified with NOBF4 and DSPE-PEG exhibited notably higher single-particle brightness with minimal quenching (3% and 8%, respectively), followed by SiO2, F127, IR806, mSiO2, and HCl (84% quenching). HCl disrupted UCNPs's crystal lattice, weakening luminescence, while mSiO2 absorbed solvent molecules, causing luminescence quenching. Energy transfer to IR806 also reduced the brightness. Additionally, a prevalence of upconversion red emission over green is observed, with the red-to-green ratio increasing with irradiance. UCNPs coated with DSPE-PEG exhibited the brightest single-particle luminescence in water, retaining 48% of its original emission due to a lower critical micelle concentration and superior water protection. In summary, the investigation provides valuable insights into the role of surface chemistry on UCNPs at the single-particle level.

2.
Nano Lett ; 23(11): 5209-5216, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37227052

RESUMEN

Upconversion nanoparticles (UCNPs) doped with lanthanides have limited brightness due to their small absorption cross section to light. However, using organic sensitizers can significantly enhance their light absorption ability. Unfortunately, the practical application of organic sensitizers has been hindered by poor stability and aggregation-caused quenching (ACQ). To address these issues, we developed a novel squaraine-based dye, SQ-739, for sensitizing upconversion luminescence (UCL). This dye has a maximum absorption at 739 nm, and shows 1 order of magnitude and 2-fold improved chemical- and photostability, compared to the commonly used cyanine-based dye IR-806, respectively. When SQ-739 is used to sensitize UCNPs, the resulting SQ-739-UCNPs exhibit excellent photostability and reduced ACQ in the presence of polar solvents. Moreover, at the single particle level, the SQ-739-UCNPs exhibit a 97-fold increase in UCL emission compared to bare UCNPs. This squaraine dye-based system represents a new design strategy for developing highly stable and efficient NIR upconversion probes.

3.
Clin Immunol ; 257: 109811, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37858752

RESUMEN

BACKGROUND: To explore the specific marker of CD8+ T cell subsets which are closely related to the prognosis and immunotherapy of patients with colon cancer. METHODS: 18 kinds of immune cell expression profile data sets were obtained from GEO database. Compared with other immune cell types, the specific markers of CD8 (+) T cells (TI-CD8) in colorectal cancer were screened. Regression analyses were used to further screen prognostic related genes and construct a prognostic evaluation model. The patients were stratified and analyzed according to the risk scores, KRAS mutation status, stage, lymphatic infiltration and other indicators. The landscape of infiltration level, mutation and copy number variation of immune subsets in high and low TI-CD8Sig score groups were compared and analyzed. The difference of drug response between high and low TI-CD8Sig score groups was analyzed. Differential expression of the model genes was verified by the HPA database. RESULTS: Six prognostic-related CD8T cell-specific gene targets were further screened, and the prognostic evaluation model was constructed. The AUC value of the model is >0.75. FAT3 and UNC13C showed a high mutation state in the low-risk group, while USH2A, MUC5B et al. specifically showed a high mutation state in the high-risk group. Compared with the low-risk group, the high-risk group had lower effective rate of drug response. The expression of PD-1 gene was positively correlated with the level of TI-CD8Sig score. CONCLUSION: The risk assessment model based on CD8T cell-specific marker genes can effectively predict the prognosis and the drug response of patients with CRC.


Asunto(s)
Neoplasias del Colon , Variaciones en el Número de Copia de ADN , Humanos , Neoplasias del Colon/genética , Neoplasias del Colon/terapia , Linfocitos T CD8-positivos , Pronóstico , Inmunoterapia , Aprendizaje Automático , Microambiente Tumoral
4.
Opt Express ; 31(15): 25318-25338, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37475340

RESUMEN

Accurate and complete 3D measurement of complex high dynamic range (HDR) surfaces has been challenging for structured light projection technique. The behavior of spraying a layer of diffuse reflection material, which will inevitably incur additional thickness. Existing methods based on additional facilities will increase the cost of hardware system. The algorithms-based methods are cost-effective and nondestructive, but they generally require redundant patterns for image fusion and model training, which fail to be suitable for practicing automated 3D measurement for complex HDR surfaces. In this paper, a HDR surface 3D reconstruction method based on sharing demodulation phase unwrapping mechanism and multi-indicators guided phase fusion strategy is proposed. The division of the exposure interval is optimized via the image entropy to generate an optimal exposure sequence. The combination of temporal-spatial binary (TSB) encoding fringe patterns with time-integration strategy and the variable exposure mode of digital mirror device (DMD)-based projector with a minimum projection exposure time of 233µs enables the proposed approach to broadly adapt complex HDR surfaces. We propose an efficient phase analysis solution called sharing mechanism that wrapped phase sequences from captured different intensity fringe images are unwrapped through sharing the same group of misaligned Gray code (MGC) decoding result. Finally, a phase sequences fusion model guided by multi-indicators, including exposure quality, phase gradient smoothness and pixel effectiveness, is established to obtain an optimum phase map for final 3D reconstruction. Comparative experiments indicate that the proposed method can completely restore the 3D topography of HDR surfaces with the images reduction of at least 65% and the measurement integrity is maintained at over 98% while preserving the measurement accuracy and excluding the outliers.

5.
Funct Integr Genomics ; 22(6): 1331-1344, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35941266

RESUMEN

Basic helix-loop-helix (bHLH) is the second largest family of transcription factors that widely exist in plants and animals, and plays a key role in a variety of biological processes. As an important forage crop worldwide, little information is available about the bHLH family in orchardgrass (Dactylis glomerata L.), although a huge number of bHLH family have been identified and characterized in plants. In this study, we performed genome-wide analysis of bHLH transcription factor family of orchardgrass and identified 132 DgbHLH genes. The phylogenetic tree was constructed by using bHLH proteins of orchardgrass, with Arabidopsis thaliana and Oryza sativa bHLH proteins, to elucidate their homology and classify them into 22 subfamilies. The results of conserved motifs and gene structure support the classification of DgbHLH family. In addition, chromosomal location and gene duplication events of DgbHLH genes were further studied. Transcriptome data exhibited that DgbHLH genes were differentially expressed in different tissues of orchardgrass. We analyzed the gene expression level of 12 DgbHLH genes in orchardgrass under three types of abiotic stresses (heat, salt, and drought). Finally, heterologous expression assays in yeast indicated that DgbHLH46 and DgbHLH128 may enhance the resistance to drought and salt stress. Furthermore, DgbHLH128 may also be involved in abiotic stress by binding to the MYC element. Our study provides a comprehensive assessment of DgbHLH family of orchardgrass, revealing new insights for enhancing gene utilization and improving forage performance.


Asunto(s)
Arabidopsis , Dactylis , Animales , Dactylis/genética , Dactylis/metabolismo , Tolerancia a la Sal/genética , Sequías , Filogenia , Arabidopsis/genética , Arabidopsis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Estrés Fisiológico/genética , Plantas , Regulación de la Expresión Génica de las Plantas
6.
Microb Pathog ; 162: 105356, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34915138

RESUMEN

AhyI is homologous to the protein LuxI and is conserved throughout bacterial species including Aeromonas hydrophila. A. hydrophila causes opportunistic infections in fish and other aquatic organisms. Furthermore, this pathogennot only poses a great risk for the aquaculture industry, but also for human public health. AhyI (expressing acylhomoserine lactone) is responsible for the biosynthesis of autoinducer-1 (AI-1), commonly referred to as a quorum sensing (QS) signaling molecule, which plays an essential role in bacterial communication. Studying protein structure is essential for understanding molecular mechanisms of pathogenicity in microbes. Here, we have deduced a predicted structure of AhyI protein and characterized its function using in silico methods to aid the development of new treatments for controlling A.hydrophila infections. In addition to modeling AhyI, an appropriate inhibitor molecule was identified via high throughput virtual screening (HTVS) using mcule drug-like databases.The AhyI-inhibitor N-cis-octadec-9Z-enoyl-l-Homoserine lactone was selected withthe best drug score. In order to understand the pocket sites (ligand binding sites) and their interaction with the selected inhibitor, docking (predicted protein binding complex) servers were used and the selected ligand was docked with the predicted AhyI protein model. Remarkably, N-cis-octadec-9Z-enoyl-l-Homoserine lactone established interfaces with the protein via16 residues (V24, R27, F28, R31, W34, V36, D45, M77, F82, T101, R102, L103, 104, V143, S145, and V168), which are involved with regulating mechanisms of inhibition. These proposed predictions suggest that this inhibitor molecule may be used as a novel drug candidate for the inhibition of auto-inducer-1 (AI-1) activity.The N-cis-octadec-9Z-enoyl-l-Homoserine lactone inhibitor molecule was studied on cultured bacteria to validate its potency against AI-1 production. At a concentration of 40 µM, optimal inhibition efficiency of AI-1 was observedin bacterial culture media.These results suggest that the inhibitor molecule N-cis-octadec-9Z-enoyl-l-Homoserine lactone is a competitive inhibitor of AI-1 biosynthesis.


Asunto(s)
Aeromonas hydrophila , Proteínas Bacterianas , 4-Butirolactona/análogos & derivados , Animales , Humanos , Percepción de Quorum
7.
BMC Infect Dis ; 22(1): 353, 2022 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-35397512

RESUMEN

BACKGROUND: The incidence of sparganosis, especially intracranial live sparganosis is very low in China. Due to the lack of typical clinical manifestations, it is difficult to make a clear preoperative diagnosis of the disease, which often leads to delays the disease and serious consequences. CASE PRESENTATION: A 23-year-old man presented with a 17-year history of intermittent seizures and right extremity numbness and weakness. Magnetic resonance imaging (MRI) showed patchy, nodular and line-like enhancement. Enzyme-linked immunosorbent assay (ELISA) detected positive antibodies to Spirometra mansoni in peripheral blood and cerebrospinal fluid (CSF). In addition, during the operation, an ivory-colored live sparganosis was removed under the precise positioning of neuronavigation, and the patient was diagnosed with cerebral sparganosis. The patient began praziquantel and sodium valproate treatment after the operation, and was followed up for 3 months. There was no recurrence of epilepsy, and the weakness and numbness of the right limb improved. CONCLUSION: Nonspecific clinical manifestations often make the diagnosis of cerebral sparganosis difficult, and a comprehensive diagnosis should be made based on epidemiological history, clinical manifestations, ELISA results and imaging findings. Surgery is the preferred method for the treatment of cerebral sparganosis, and more satisfactory results can be achieved under the precise positioning of neuronavigation.


Asunto(s)
Esparganosis , Spirometra , Adulto , Animales , Humanos , Hipoestesia/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Praziquantel/uso terapéutico , Esparganosis/diagnóstico , Esparganosis/tratamiento farmacológico , Esparganosis/cirugía , Adulto Joven
8.
Appl Opt ; 61(30): 9028-9036, 2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36607032

RESUMEN

3D measurement methods of a high-dynamic-range (HDR) surface based on adaptive fringe projection have aroused extensive research interest. They tend to pixel-wise adjust the fringe projection intensity to ensure full-field phase quality in light or dark regions, which has two problems: (1) traditional image intensity-based temporal phase unwrapping (TPU) is susceptible to noise in dark regions, and (2) it is time-consuming to project orthogonal fringe patterns for coordinate mapping and 3D reconstruction. Aiming to address these issues, we present an efficient adaptive fringe projection method where misaligned Gray code patterns are adopted to remove the phase error induced by low-frequency fringe patterns. Compared with traditional image intensity-based TPU, misaligned Gray-code-based TPU provides a better noise-suppression effect in dark regions, as Gray codes are generally better preserved than image intensity. Moreover, the images captured in the coordinate mapping process are shared for optimal projection intensity calculation and 3D reconstruction to reduce the number of total projection patterns, thus improving measurement efficiency. Extensive contrast experiments are conducted to demonstrate that the proposed method retrieves the 3D shapes of micro-scale HDR surfaces with high accuracy and a minimum number of projection patterns on the premise of high measurement integrity.

9.
Brain Behav Immun ; 98: 283-298, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34455059

RESUMEN

OBJECTIVE: Cognitive impairment is a common neurological disease of which NLRP3-related neuroinflammation has been demonstrated to be an essential mediator. Previous studies have indicated that long non-coding RNAs (lncRNAs) are critical for the development of neurological disorders. However, the roles and functions of lncRNA 4344 in neuroinflammation during cognitive impairment are unknown and need to be further elucidated. METHODS: Lipopolysaccharide (LPS)-induced rat cognitive impairment and rat microglia (RM) cell inflammation models were established in vitro and in vivo. The Morris water maze test was used to evaluate the cognitive behavior of the rats. Gene expression was assessed using real-time quantitative polymerase chain reaction, and protein levels using enzyme-linked immunosorbent assay, or western blot analysis. The targeting relationship between lncRNA 4344, miR-138-5p, and NLRP3 was identified using bioinformatics analysis and a dual-luciferase reporter gene assay. Hematoxylin-Eosin and Nissl stainings, terminal deoxynucleotidyl transferase dUTP nick end labeling, or immunofluorescence staining assays were performed to detect pathological changes, neuronal apoptosis, or positive cells in hippocampal tissues, respectively. RESULTS: The expression levels of lncRNA 4344 and NLRP3 were upregulated in the hippocampal tissues of LPS-treated rats and RM cells, and showed a strong positive correlation between each other. LncRNA 4344 overexpression further enhanced the expression of NLRP3 and its downstream genes (caspase-1, IL-1ß, and IL-18), as well as neuronal apoptosis in LPS-stimulated RM cells, whereas lncRNA 4344 silencing attenuated the inflammatory injuries. Moreover, miR-138-5p was the direct target of lncRNA 4344 and was downregulated in the RM cell inflammation model. We also found that miR-138-5p directly reduced the expression of NLRP3 and its downstream genes. Subsequently, the results of the animal experiments showed that the lncRNA 4344/miR-138-5p/NLRP3 axis plays an essential role in regulating the cognitive behavior, pathological changes and apoptosis of hippocampal neurons, expression of inflammation-related factors (NLRP3, caspase-1, IL-1ß, and IL-18), and microglial activation in LPS-induced cognitive impairment rats. CONCLUSION: Our results demonstrated for the first time that lncRNA 4344 regulates NLRP3-related neuroinflammation and cognitive impairment by targeting miR-138-5p, providing a possible target for the treatment of diseases characterized by a cognitive deficit.


Asunto(s)
Disfunción Cognitiva , MicroARNs , ARN Largo no Codificante , Animales , Disfunción Cognitiva/genética , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Enfermedades Neuroinflamatorias , ARN Largo no Codificante/genética , Ratas
10.
BMC Anesthesiol ; 20(1): 193, 2020 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-32758153

RESUMEN

BACKGROUND: There is no consensus on whether intraoperative hypotension is associated with postoperative cognitive impairment. Hence, we performed a meta-analysis to evaluate the correlation of intraoperative hypotension and the incidence of postoperative delirium (POD) or postoperative cognitive dysfunction (POCD). METHODS: We searched PubMed, Embase, and Cochrane Library databases to find randomized controlled trials (RCTs) in which reported the relationship between intraoperative hypotension and POD or POCD. The retrieval time is up to January 2020, without language restrictions. Quality assessment of the eligible studies was conducted by two researchers independently with the Cochrane evaluation system. RESULTS: We analyzed five eligible RCTs. Based on the relative mean arterial pressure (MAP), participants were divided into low-target and high-target groups. For the incidence of POD, there were two studies with 99 participants in the low-target group and 94 participants in the high-target pressure group. For the incidence of POCD, there were four studies involved 360 participants in the low-target group and 341 participants in the high-target group, with a study assessed both POD and POCD. No significant difference between the low-target and the high-target group was observed in the incidence of POD (RR = 3.30, 95% CI 0.80 to 13.54, P = 0.10), or POCD (RR = 1.26, 95% CI 0.76 to 2.08, P = 0.37). Furthermore, it also demonstrates that intraoperative hypotension prolonged the length of ICU stay, but did not increased the mortality, the length of hospital stay, and mechanical ventilation (MV) time. CONCLUSIONS: There is no significant correlation between intraoperative hypotension and the incidence of POD or POCD.


Asunto(s)
Hipotensión/fisiopatología , Complicaciones Intraoperatorias/fisiopatología , Complicaciones Cognitivas Postoperatorias/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Humanos , Hipotensión/diagnóstico , Hipotensión/epidemiología , Unidades de Cuidados Intensivos/tendencias , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/epidemiología , Tiempo de Internación/tendencias , Complicaciones Cognitivas Postoperatorias/diagnóstico , Complicaciones Cognitivas Postoperatorias/epidemiología
11.
BMC Microbiol ; 15: 214, 2015 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-26474554

RESUMEN

BACKGROUND: Bacteria use transcriptional regulation to respond to environmental stresses. Specifically, exposure to antibacterial drugs is deemed to be an atypical stress, and altering transcriptional regulation in response to such stress can increase bacterial drug resistance. However, only a few transcription factors that regulate drug resistance have been reported. RESULTS: In the present study, a GntR family transcription factor, encoded by the MSMEG_0535 (Ms0535) gene, was shown to be an isoniazid (INH) resistance regulator in Mycobacterium smegmatis. When the Ms0535 gene was overexpressed, cells showed a significant increase in INH resistance. First, the interaction between Ms0535 and its own promoter was determined, and a conserved 26-bp palindromic DNA binding motif was identified using electrophoretic mobility shift and DNaseI footprinting assays. Second, quantitative reverse transcription-PCR assays showed that Ms0535 acted as a transcriptional activator, and positively regulated its own expression, as well as that of a permease encoded by the MSMEG_0534 (Ms0534) gene. Similar to the case for the Ms0535 gene, a recombinant Ms0534-overexpressing strain also exhibited increased INH resistance compared with the wild-type strain. Furthermore, we showed that Ms0535 and Ms0534 deletion strains were more sensitive to INH than the wild-type strain. Interestingly, overexpressing Ms0534 in the Ms0535 deletion strain enhanced its INH resistance. In contrast, the Ms0534 deletion strain was still sensitive to INH even when Ms0535 was overexpressed. These findings suggest that Ms0534 is an effector protein that affects INH resistance in M. smegmatis. CONCLUSIONS: In summary, the GntR transcriptional regulator Ms0535 positively regulates INH resistance by transcriptionally regulating the expression of the Ms0534 permease in M. smegmatis. These results improve our understanding of the role of transcriptional regulation in INH drug resistance in mycobacteria.


Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Regulación Bacteriana de la Expresión Génica , Isoniazida/farmacología , Proteínas de Transporte de Membrana/metabolismo , Mycobacterium smegmatis/efectos de los fármacos , Factores de Transcripción/metabolismo , Proteínas de Transporte de Membrana/genética , Mycobacterium smegmatis/genética , Factores de Transcripción/genética
12.
Nanoscale Adv ; 6(11): 2945-2953, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38817426

RESUMEN

Single-particle detection and sensing, powered by Förster resonance energy transfer (FRET), offers precise monitoring of molecular interactions and environmental stimuli at a nanometric resolution. Despite its potential, the widespread use of FRET has been curtailed by the rapid photobleaching of traditional fluorophores. This study presents a robust single-particle FRET platform utilizing upconversion nanoparticles (UCNPs), which stand out for their remarkable photostability, making them superior to conventional organic donors for energy transfer-based assays. Our comprehensive research demonstrates the influence of UCNPs' size, architecture, and dye selection on the efficiency of FRET. We discovered that small particles (∼14 nm) with a Yb3+-enriched outermost shell exhibit a significant boost in FRET efficiency, a benefit not observed in larger particles (∼25 nm). 25 nm UCNPs with an inert NaLuF4 shell demonstrated a comparable level of emission enhancement via FRET as those with a Yb3+-enriched outermost shell. At the single-particle level, these FRET-enhanced UCNPs manifested an upconversion green emission intensity that was 8.3 times greater than that of their unmodified counterparts, while maintaining notable luminescence stability. Our upconversion FRET system opens up new possibilities for developing more effective high-brightness, high-sensitivity single-particle detection, and sensing modalities.

13.
J Biochem ; 176(1): 43-54, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38444151

RESUMEN

Protection against oxidative stress is a vital defense mechanism for Mycobacterium tuberculosis within the host. However, few transcription factors that control bacterial antioxidant defense are known. Here, we present evidence that SdrR, encoded by the MSMEG_5712 (Ms5712) gene, functions as an oxidative stress response regulator in Mycobacterium smegmatis. SdrR recognizes an 11-bp motif sequence in the operon's upstream regulatory region and negatively regulates the expression of short-chain dehydrogenases/reductases (SDR). Overexpressing sdrR inhibited SDR expression, which rendered the strain oxidative more stress-sensitive. Conversely, sdrR knockout alleviates SDR repression, which increases its oxidative stress tolerance. Thus, SdrR responds to oxidative stress by negatively regulating sdr expression. Therefore, this study elucidated an underlying regulatory mechanism behind mycobacterial oxidative stress adaptation.


Asunto(s)
Antioxidantes , Proteínas Bacterianas , Mycobacterium smegmatis , Estrés Oxidativo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Mycobacterium smegmatis/metabolismo , Mycobacterium smegmatis/genética , Antioxidantes/metabolismo , Regulación Bacteriana de la Expresión Génica , Mycobacterium tuberculosis/metabolismo , Operón
14.
Front Mol Biosci ; 11: 1420585, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818356

RESUMEN

[This corrects the article DOI: 10.3389/fmolb.2023.1270979.].

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124328, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38669986

RESUMEN

We designed and developed the probe W-3 for detection of Cu2+. The results showed probe can selectively detect Cu2+, accompanied by noticeable color change. The probe can detect the Cu2+ in water samples and drinks based on absorption detection. In addition, the combination of portable test paper and the smartphone platform obtained great convenience for on-site and visual detection of Cu2+, with satisfactory sensitivity and reliability. More importantly, the fluorescence probe W-3 can be used for the detection of Cu2+ in cells and mice. Therefore, the W-3 provided potential chemical tools for detecting Cu2+ in vitro and vivo.


Asunto(s)
Cobre , Colorantes Fluorescentes , Espectrometría de Fluorescencia , Cobre/análisis , Colorantes Fluorescentes/química , Animales , Espectrometría de Fluorescencia/métodos , Humanos , Ratones , Imagen Óptica/métodos , Células HeLa , Límite de Detección
16.
Anal Chim Acta ; 1315: 342817, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38879215

RESUMEN

Diabetes has become one of the most common endocrine and metabolic diseases threatening human health, which can induce mitochondrial dysfunction and exacerbate the excessive production of reactive oxygen species (ROS). Among them, ONOO- level fluctuation was closely related to diabetes. Hence, it is of great significance to develop a near-infrared fluorescence probe for visualizing ONOO- level fluctuations in diabetes. In this paper, we constructed a fluorescence probe YBL with dicyano-isophorone derivative as fluorophore and diphenyl phosphate as ONOO- response site, which can detect ONOO- with the low detection limit (39.8 nM) and exhibit excellent selectivity and sensitivity. The probe YBL has been applied to monitor intracellular ONOO- level fluctuations. Meanwhile, the image results showed that high sugar promoted the increase of ONOO- level in cells. More important, the probe YBL can be used for imaging in mice, and the results showed that content of ONOO- was increased in diabetic mice. Therefore, the probe YBL provided a tool for understanding diabetes progression by imaging ONOO-.


Asunto(s)
Diabetes Mellitus Experimental , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Ratones , Humanos , Diabetes Mellitus Experimental/inducido químicamente , Imagen Óptica , Rayos Infrarrojos , Límite de Detección
17.
Anal Methods ; 16(24): 3831-3838, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38828794

RESUMEN

We designed and prepared probe W-1 for the detection of H2O2. W-1 showed excellent selectivity for H2O2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2 concentration (0-100 µM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H2O2 fluctuation of the diabetic process in mice, and the results showed an increase in H2O2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.


Asunto(s)
Diabetes Mellitus Experimental , Colorantes Fluorescentes , Peróxido de Hidrógeno , Mitocondrias , Peróxido de Hidrógeno/metabolismo , Animales , Mitocondrias/metabolismo , Colorantes Fluorescentes/química , Ratones , Humanos , Colorimetría/métodos , Imagen Óptica/métodos
18.
Biosens Bioelectron ; 254: 116233, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38518563

RESUMEN

Intracellular microenvironment (viscosity and polarity) and peroxynitrite ions (ONOO-) are involved in maintaining cell morphology, cell function, and signaling so that it is crucial to explore their level changes in vitro and vivo. In this work, we designed and synthesized a mitochondria-targeted fluorescence probe XBL for monitoring the dynamic changes of viscosity, polarity, and ONOO- based on TICT and ICT mechanism. The fluorescence spectra showed obvious changes for polarity at 500 nm as well as ONOO- and viscosity at 660 nm, respectively. The XBL can image simultaneously viscosity, polarity, and ONOO- in cells, and the results showed excess ONOO- leaded to the increase of viscosity in mitochondrial. The ferroptosis process was accompanied by increase of intracellular viscosity and ONOO- levels (or decrease of polarity), which allowed us to better understand the relevant physiological and pathological processes. The XBL can distinguish normal cells and cancerous cells by the fluorescence intensity changes in green and red channels, and image viscosity in inflamed mice. Thus, XBL can provided the chemical tool to understand the physiological and pathological mechanisms of disease by simultaneous detection of viscosity, polarity and ONOO-.


Asunto(s)
Técnicas Biosensibles , Colorantes Fluorescentes , Ratones , Animales , Viscosidad , Células RAW 264.7 , Mitocondrias , Ácido Peroxinitroso
19.
Biomed Pharmacother ; 157: 113927, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36462316

RESUMEN

The G protein-coupled P2Y12 receptor (P2Y12R) was cloned in platelets and found to play a key role in maintaining platelet function in hemostasis and thrombosis, and these effects could be mediated by the P2Y12R. However, it has recently been found that P2Y12R-mediated the progression of tumor through interactions between platelets and tumor and stromal cells, as well as through products secreted by platelets. During tumor progression, tumor cells or other cells in the tumor microenvironment (such as immune cells) can secrete large amounts of ATP into the extracellular matrix, and extracellular ATP can be hydrolyzed into ADP. ADP is a P2Y12R activator and plays an important regulatory role in the proliferation and metastasis of tumor cells. P2Y12R is involved in platelet-cancer cell crosstalk and become a potential target for anticancer therapy. Moreover, tumor progression can induce pain, which seriously affects the quality of life of patients. P2Y12R is expressed in microglia and mediates the activities of microglial and participates in the occurrence of cancer pain. Conversely, inhibiting P2Y12R activation and down-regulating its expression has the effect of inhibiting tumor progression and pain. Therefore, P2Y12R can be a common therapeutic target for both. In this article, we explored the potential link between P2Y12R and cancer, discussed the intrinsic link of P2Y12R in cancer pain and the pharmacological properties of P2Y12R antagonists in the treatment of both.


Asunto(s)
Dolor en Cáncer , Neoplasias , Humanos , Antagonistas del Receptor Purinérgico P2Y/farmacología , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Dolor en Cáncer/metabolismo , Calidad de Vida , Plaquetas , Dolor/metabolismo , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Microambiente Tumoral
20.
Genes Dis ; 10(5): 2109-2124, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37492736

RESUMEN

This study aims to identify the inflammatory factor-related genes which help to predict the prognosis of patients with colorectal cancer. GSEA (Gene Set Enrichment Analysis) was used to acquire inflammation-related genes and the corresponding expression information was collected from TCGA database to determine the DEGs (differentially-expressed genes) in CRC patients. We conducted enrichment analysis and PPI (protein-protein interaction) of these DEGs. Besides, key genes that are both differentially-expressed and prognosis-related were screened out, which were used to establish the prognostic model. We obtained 79 DEGs and 19 prognostic genes, 10 prognostic-related differential genes were eventually screened. These genes were used to construct the prognostic model. We also identified that the immune infiltration score of macrophages between different risk groups was significantly different and similar distinction was witnessed in immune function score of APC (antigen-presenting cell) co-stimulation and type I IFN (interferon) response.

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