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1.
Mol Cell Biochem ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743321

RESUMO

The aim is to investigate the relationship between serum coagulation parameters (PT, APTT, D-D and FDP) before hospitalization and recurrence of chronic subdural hematoma (CSDH). 236 patients with CSDH who were diagnosed for the first time and had complete medical records were followed up for at least 90 days. Fifty patients (21.2%) had relapsed. Univariate analysis was conducted including general data, imaging data and test results. Serum coagulation parameters (PT, APTT, D-D and FDP) were detected for all CSDH patients. The study identified several factors that exhibited a significant correlation with chronic subdural hematoma (CSDH) recurrence. These factors included advanced age (p = 0.01), hypertension (p = 0.04), liver disease (p = 0.01), anticoagulant drug use (p = 0.01), antiplatelet drug use (p = 0.02), bilateral hematoma (p = 0.02), and single-layer hematoma (p = 0.01). In addition, the presence of fibrin/fibrinogen degradation products (FDP) exceeding 5 mg/L demonstrated a significant relationship with CSDH recurrence (P < 0.05). Notably, the combined assessment of D-dimer (D-D) and FDP exhibited a significant difference, particularly regarding recurrence within 30 days after surgery (P < 0.05). The simultaneous elevation of serum FDP and D-D levels upon admission represents a potentially novel predictor for CSDH recurrence. This finding is particularly relevant for patients who experience recurrence within 30 days following surgical intervention. Older individuals with CSDH who undergo trepanation and drainage should be closely monitored due to their relatively higher recurrence rate.

2.
Aging (Albany NY) ; 16(8): 6990-7008, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38613810

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) comprises primary and secondary injuries, the latter of which induces increased inflammation and apoptosis and is more severe. Activating transcription factor 6 (ATF6) is a type-II transmembrane protein in the endoplasmic reticulum (ER). ATF6 target genes could improve ER homeostasis, which contributes to cryoprotection. Hence, we predict that ATF6 will have a protective effect on brain tissue after ICH. METHOD: The ICH rat model was generated through autologous blood injection into the right basal ganglia, the expression of ATF6 after ICH was determined by WB and IF. The expression of ATF6 was effectively controlled by means of intervention, and a series of measures was used to detect cell death, neuroinflammation, brain edema, blood-brain barrier and other indicators after ICH. Finally, the effects on long-term neural function of rats were measured by behavioral means. RESULT: ATF6 was significantly increased in the ICH-induced brain tissues. Further, ATF6 was found to modulate the expression of cystathionine γ-lyase (CTH) after ICH. Upregulation of ATF6 attenuated neuronal apoptosis and inflammation in ICH rats, along with mitigation of ICH-induced brain edema, blood-brain barrier deterioration, and cognitive behavior defects. Conversely, ATF6 genetic knockdown induced effects counter to those aforementioned. CONCLUSIONS: This study thereby emphasizes the crucial role of ATF6 in secondary brain injury in response to ICH, indicating that ATF6 upregulation may potentially ameliorate ICH-induced secondary brain injury. Consequently, ATF6 could serve as a promising therapeutic target to alleviate clinical ICH-induced secondary brain injuries.


Assuntos
Fator 6 Ativador da Transcrição , Barreira Hematoencefálica , Hemorragia Cerebral , Cistationina gama-Liase , Modelos Animais de Doenças , Ratos Sprague-Dawley , Animais , Hemorragia Cerebral/metabolismo , Ratos , Fator 6 Ativador da Transcrição/metabolismo , Fator 6 Ativador da Transcrição/genética , Masculino , Cistationina gama-Liase/metabolismo , Cistationina gama-Liase/genética , Barreira Hematoencefálica/metabolismo , Apoptose , Edema Encefálico/metabolismo , Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia
3.
Mycology ; 15(1): 85-90, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558838

RESUMO

Invasive aspergillosis (IA) is the most severe type of Aspergillus infection. Yunnan has developed agriculture, and the proportion of triazole-resistant A. fumigatus induced by triazole fungicides is much higher than that in other regions of China. Inhalation of triazole-resistant A. fumigatus is one of the main factors inducing IA. We gathered five strains of A. fumigatus from the sputum or bronchoalveolar lavage fluid (BALF) of patients with IA in Yunnan. Subsequent testing showed that all of these strains were resistant to triazoles and harboured mutations in the tandem repeat sequence of the cyp51A promoter region, suggesting that they may be triazole-resistant A. fumigatus present in the environment.

4.
Talanta ; 274: 126120, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38640603

RESUMO

Peroxynitrite (ONOO-) and cell plasma membrane (CPM) are two key factors in cell pyroptosis during the progression of abdominal aortic aneurysm (AAA). However, their combined temporal and spatial roles in initiating AAA pathogenesis remain unclear. Herein, we developed a two-photon fluorescence probe, BH-Vis, enabling real-time dynamic detection of CPM and ONOO- changes, and revealing their interplay in AAA. BH-Vis precisely targets CPM with reduced red fluorescence intensity correlating with diminished CPM tension. Concurrently, a blue shift of the fluorescence signal of BH-Vis occurs in response to ONOO- offering a reliable ratiometric detection mode with enhanced accuracy by minimizing external testing variables. More importantly, two photon confocal imaging with palmitic acid (PA) and ganglioside (GM1) manipulation, which modulating cell pyroptosis, showcases reliable fluorescence fluctuations. This groundbreaking application of BH-Vis in a mouse AAA model demonstrates its significant potential for accurately identifying cell pyroptosis levels during AAA development.


Assuntos
Aneurisma da Aorta Abdominal , Membrana Celular , Imagem Óptica , Ácido Peroxinitroso , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/patologia , Ácido Peroxinitroso/metabolismo , Animais , Camundongos , Membrana Celular/metabolismo , Membrana Celular/química , Humanos , Corantes Fluorescentes/química , Piroptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Masculino , Fótons
5.
J Hazard Mater ; 469: 134003, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38492394

RESUMO

In this study, we have effectively prepared a novel fluorescent probe named HDXM based on benzopyran derivatives for the ultrafast detection (within 3 s) of SO2 derivatives or biogenic amines. HDXM showed a noticeable color change after the addition of SO2 derivatives (from purple to colorless) or biogenic amines (from purple to blue), indicating that HDXM can identify two analytes with the naked eye. It is worth noting that HDXM can be used to detect SO2 derivatives in actual sugar samples, and to image HSO3-/SO32- in living cells. More importantly, sensing labels (HDXM-loaded filter paper or agarose hydrogel) enable real-time visual monitoring of salmon freshness through colorimetric and fluorescence dual channels. Compared with the Chinese national standard method, the sensing label is an effective tool for evaluating the freshness of fish. Benefiting from its excellent solubility and fluorescence performance, HDXM can be used as a versatile fluorescent material in various applications, including flexible films, glass coatings, impregnating dyes, printing, and fingerprint ink. HDXM is expected to be a promising and valuable multifunctional tool for food safety and fluorescent materials.


Assuntos
Aminas Biogênicas , Corantes Fluorescentes , Animais , Fluorescência , Alimentos Marinhos/análise , Carboidratos , Peixes
6.
J Cancer Res Clin Oncol ; 149(17): 16043-16053, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37688630

RESUMO

Gastric cancer is a kind of tumor with strong heterogeneity. Long noncoding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors. In this study, we divided all TCGA gastric cancer patients into the whole, intestinal and diffuse cohorts for further analysis, and constructed competitive endogenous RNA network and evaluated immune cells using CIBERSORTx. The support vector machines recursive feature elimination (SVM-RFE) was used for screening significant signatures and the support vector machines (SVM) for establishing model predicting the lymph node metastasis. The performance of SVM model was good in the intestinal and diffuse cohort, while the model in the whole cohort was relatively poor. Some important co-expression patterns between immune cells and ceRNAs network indicated significant correlation CD70 with dendritic cells and so on. Our research inferred competing endogenous RNA network of lymph node metastasis and built an excellent predicting model.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , RNA , Metástase Linfática , Neoplasias Gástricas/genética , RNA Longo não Codificante/genética , MicroRNAs/genética , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica
7.
Aging (Albany NY) ; 15(17): 9041-9058, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37698533

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and disability rate, and neuroinflammation is involved in secondary brain injury. Galectin-3 (Gal-3) is one of the scaffold proteins of Galectins. Studies have indicated that Gal-3 plays an important role in the physiological and pathological state of the nervous system. Here we focus on the role of Gal-3 in ICH, especially in neuroinflammation. METHODS: Injection of autologous blood into the right basal ganglia was used to simulate ICH injury, and the level of Gal-3 in brain was regulated by related means. The changes of Gal-3 were detected by western blot and immunofluorescence, the level of neuroinflammation by immunofluorescence staining and ELISA. Apoptosis and neuron loss were detected by TUNEL staining FJB staining and Nissl staining, and neurological deficits were judged by neurobehavioral tests. RESULTS: The protein level of Gal-3 increased at 24 h after ICH. Downregulation of Gal-3 level can reduce the infiltration of M1-type microglia and peripheral inflammatory cells, thus alleviating post-ICH neuroinflammation, and reducing cell apoptosis and neuron loss in brain tissue. ICH-induced neurological damage was rescued. Meanwhile, the promotion in the expression level of Gal-3 increased neuroinflammatory activation and nerve cell death, aggravating ICH-induced brain injury. CONCLUSIONS: This study proves that Gal-3 is involved in neuroinflammation and nerve damage after ICH. Gal-3 expression should not be encouraged early on to prevent neuroinflammation. which provides a new possibility for clinical treatment for ICH patients.


Assuntos
Lesões Encefálicas , Galectina 3 , Humanos , Receptor 4 Toll-Like , Microglia , Doenças Neuroinflamatórias , Galectinas , Hemorragia Cerebral , Fenótipo , Hemorragias Intracranianas
8.
Materials (Basel) ; 16(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37445040

RESUMO

In this paper, the response characteristics of wave propagation in entangled metallic wire materials (EMWMs) are investigated by acoustic emission. The frequency, amplitude of wave emission, and the pre-compression force of the specimen can be adjusted in the experimental setup. EMWM specimens fabricated from stainless steel wires and with different design parameters are tested in this work. The results show that waves of different amplitudes propagate in EMWMs with approximate linear characteristics and the fluctuation coefficient of wave passing ratios is calculated below 15%. The response spectrum of passing waves shows a distinct single-peak characteristic, with the peak response at approximately 14 kHz. The parameters of pre-compression force, porosity, wire diameter, helix diameter, specimen height, and the layered structure of specimens have no significant effect on the frequency characteristics but moderately affect the wave passing ratios. Notably, EMWMs exhibit a lower wave passing ratio (ranging from 0.01 to 0.18) compared to aluminum alloy and natural rubber. The characteristics of response spectrums can be successfully reproduced by the finite element simulation. This work demonstrates EMWMs' potential as an acoustic frequency vibration isolation material, offering excellent performance and engineering design convenience.

9.
J Cancer Res Clin Oncol ; 149(14): 13163-13173, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37474682

RESUMO

BACKGROUND: Accumulating evidence suggests that anoikis resistance is a key process in cancer cell metastasis, making it an attractive therapeutic target. Therefore, anoikis may become a new treatment for gastric cancer. METHODS: We used the univariate Cox regression method to screen gastric cancer-related anoikis genes, and a prognostic risk model was established. We analyzed differences between high- and low-risk groups in terms of tumor infiltrating immune cells, gene mutation signatures, and treatment of gastric cancer. Analysis of model associated genes at single-cell resolution was performed. RESULTS: We filtered to 12 anoikis-related genes and built a prognostic risk model using seven of them, which performed well in multiple datasets. Patients with CCDC178 mutations had a worse prognosis. We also found that patients at low risk were more likely to benefit from chemotherapy and immunotherapy. ERBB2 was found to be highly expressed in epithelial cells and fibroblasts. Our analysis also indicated that gastric cancer samples with high infiltration of iCAFs had a worse prognosis. CONCLUSION: Seven anoikis-related genes were selected to establish a risk model. The model can be used to predict the prognosis of patients and guide the drug treatment, which provides a new idea for the evaluation and treatment of gastric cancer patients.

10.
Biosens Bioelectron ; 237: 115453, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37331101

RESUMO

As one of the important means for eukaryotic cells to maintain homeostasis, autophagy allows for transporting deformed biomacromolecules and damaged organelles to lysosome for digestion and degradation. The process of autophagy entails the merging of autophagosomes and lysosomes, culminating in the breakdown of biomacromolecules. This, in turn, leads to a change in lysosomal polarity. Therefore, fully understanding the changes of lysosomal polarity during autophagy is of significance to the study of membrane fluidity and enzymatic reaction. However, the shorter emission wavelength has greatly damaged the imaging depth, thus seriously limiting its biological application. Therefore, in this work, a near infrared in and out lysosome-targeted polarity-sensitive probe NCIC-Pola was developed. The fluorescence intensity of NCIC-Pola showed an approximate 1160-fold increase when the polarity decreased under two-photon excitation (TPE). In addition, the excellent fluorescence emission wavelength (692 nm) enabled the deep imaging analysis of scrap leather induced autophagy in vivo.


Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes , Corantes Fluorescentes/metabolismo , Autofagia , Microscopia de Fluorescência/métodos , Imagem Óptica , Lisossomos/metabolismo
11.
World J Stem Cells ; 15(4): 150-164, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37180997

RESUMO

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar-capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.

12.
Talanta ; 256: 124304, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36739743

RESUMO

As a novel pattern of regulated cell death (RCD), Ferroptosis is induced by lipid peroxide-dependent iron accumulation, which is associated with reactive oxygen species (ROS). Ferroptosis regulates cell death via ROS accumulation-related lipid peroxides accumulation, affecting the structure and polarity of lipid droplets (LDs). Compared with reactive fluorescent probes, environment-sensitive fluorescent probes allow for maximum preservation of the intracellular environment while monitoring metabolic activity in situ, resulting in more accurate monitoring results. In this study, a polarity-sensitive two-photon fluorescent probe with anchoring capacity in LDs, LIP-Pola, is reported and applied to monitor the polarity of LDs during cell Ferroptosis by in situ imaging analysis of cell Ferroptosis via LDs polarity changes. Additionally, Paclitaxel is shown to increase the Ferroptosis level from data of cells and tumor tissue sections, suggesting that Paclitaxel may deactivate tumor cells by regulating Ferroptosis.


Assuntos
Antineoplásicos , Ferroptose , Gotículas Lipídicas/metabolismo , Espécies Reativas de Oxigênio , Corantes Fluorescentes/química , Peróxidos Lipídicos/metabolismo , Peróxidos Lipídicos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo
13.
Front Public Health ; 10: 974281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339220

RESUMO

Objective: To explore the effectiveness of formative evaluation in the mentoring of student nursing interns in an emergency department. Methods: A total of 144 intern nursing students in the emergency department of a tertiary care hospital in Fuzhou were selected as the study subjects from July 2020 to February 2021. Adopting quasi-experimental studies methods, the students were divided into the experiment group (n = 74) and the control group (n = 70), based on their practicing rotation times. Formative evaluation methods such as in-person interviews, clinical scenario simulations, and clinical operation skills exams were conducted in the experiment group, while traditional summative evaluation methods were adopted for the control group. At the end of the intern period, a unified examination paper on professional knowledge concerning the emergency department, a cardiopulmonary resuscitation skill assessment, and a self-rating scale of self-directed learning was employed to evaluate professional theory performance, clinical practice ability, self-directed learning ability, and academic satisfaction among the nursing students, respectively. Results: The professional theoretical performance, clinical practice ability assessment scores, academic satisfaction, and self-directed learning abilities of the nursing students were significantly higher in the experiment group compared with the control group (P < 0.05). Conclusion: The application of formative evaluation during the mentoring of student intern nurses in an emergency department improved their professional theoretical performance, clinical practice skills, academic satisfaction, and self-directed learning abilities.


Assuntos
Tutoria , Estudantes de Enfermagem , Humanos , Competência Clínica , Aprendizagem , Serviço Hospitalar de Emergência
14.
Front Cell Infect Microbiol ; 12: 949840, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36250052

RESUMO

Odontogenic brain and pulmonary abscesses are extremely rare infectious diseases. It is mainly caused by the upward or downward transmission of local infection or blood-borne spread. In recent years, with the wide application of some novel testing methods in clinical practice, the diagnosis of unexplained infections such as odontogenic abscesses in different organs has gradually become clear. We report a case of a 21-year-old male who was healthy and had not received any oral treatment before onset. He started with acute gastroenteritis-related symptoms, then developed meningitis-related symptoms seven days later with septic shock. No obvious abscess lesions were found on head computed tomography (CT) at admission, and the etiology was not clear by routine examination, which was very easy to misdiagnose as a serious infection caused by intestinal pathogens. But odontogenic pathogens were found both in his blood and cerebrospinal fluid through metagenomic next-generation sequencing (mNGS) analysis. Subsequently, rechecked imaging examination displayed multiple brain and pulmonary abscesses. Finally, it was diagnosed as an odontogenic brain and pulmonary abscess. After an extremely lengthy anti-infection course (13 weeks of intravenous antibiotics plus 2 weeks of oral antibiotics) and surgery, the patient was improved and discharged from the hospital. From this case, we could see that the development of new diagnostic technologies such as mNGS plays an important role in the early and confirmed diagnosis of diseases previously difficult to diagnose such as odontogenic polymicrobial infections and ultimately helps to improve the prognosis of these patients.


Assuntos
Gastroenterite , Abscesso Pulmonar , Adulto , Antibacterianos , Encéfalo/diagnóstico por imagem , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Metagenoma , Adulto Jovem
15.
Front Genet ; 13: 922074, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035150

RESUMO

Background: Increasing evidences show a clinical significance in the interaction between hypoxia and prostate cancer. However, reliable prognostic signatures based on hypoxia have not been established yet. Methods: We screened hypoxia-related gene modules by weighted gene co-expression network analysis (WGCNA) and established a hypoxia-related prognostic risk score (HPRS) model by univariate Cox and LASSO-Cox analyses. In addition, enriched pathways, genomic mutations, and tumor-infiltrating immune cells in HPRS subgroups were analyzed and compared. HPRS was also estimated to predict immune checkpoint blockade (ICB) therapy response. Results: A hypoxia-related 22-gene prognostic model was established. Furthermore, three independent validation cohorts showed moderate performance in predicting biochemical recurrence-free (BCR-free) survival. HPRS could be a useful tool in selecting patients who can benefit from ICB therapy. The CIBERSORT results in our study demonstrated that hypoxia might act on multiple T cells, activated NK cells, and macrophages M1 in various ways, suggesting that hypoxia might exert its anti-tumor effects by suppressing T cells and NK cells. Conclusion: Hypoxia plays an important role in the progression of prostate cancer. The hypoxia-derived signatures are promising biomarkers to predict biochemical recurrence-free survival and ICB therapy responses in patients with prostate cancer.

16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(3): 551-560, 2022 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-35788525

RESUMO

Microfluidics is the science and technology to manipulate small amounts of fluids in micro/nano-scale space. Multiple modules could be integrated into microfluidic device, and due to its advantages of microminiaturization and controllability, microfluidics has drawn extensive attention since its birth. In this paper, the literature data related to microfluidics research from January 1, 2006 to December 31, 2021 were obtained from Web of Science Core Collection database. CiteSpace 5.8.R3 software was used for bibliometrics analysis, so as to explore the research progress and development trends of microfluidics research at home and abroad. Based on the analysis of 50 129 articles, it could be seen that microfluidics was a hot topic of global concern, and the United States had a certain degree of authority in this field. Massachusetts Institute of Technology and Harvard University not only had a high number of publications, but also had strong influence and extensive cooperation network. Combined with ultrasonic, surface modification and sensor technology, researchers constructed paper-based microfluidic, droplet microfluidic and digital microfluidic platforms, which were applied in the field of immediate diagnosis, nucleic acid and circulating tumor cell analysis of in vitro diagnosis and organ-on-a-chip. China was one of the countries with a high level of research in the field of microfluidics, while the industrialization of high-end products needed to be improved. As people's demand for disease risk prediction and health management increased, promoting microfluidic technological innovation and achievement transformation is of great significance to safeguard people's life and health.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , China , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
17.
Chem Sci ; 13(18): 5363-5373, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35655567

RESUMO

Over recent years, fluorescent probes exhibiting simultaneous responses to multiple targets have been developed for in situ, real-time monitoring of cellular metabolism using two photon fluorescence sensing techniques due to numerous advantages including ease of operation, rapid reporting, high resolution, long visualization time and being non-invasive. However, due to interference from different fluorescence channels during simultaneous monitoring of multiple targets and the lack of ratiometric capability amongst the available probes, the accuracy in tracing metabolic processes has been restricted. With this research, using a through-bond energy transfer (TBET) mechanism, we designed a viscosity and peroxynitrite (ONOO-) mitochondria-targeting two-photon ratiometric fluorescent probe Mito-ONOO. Our results indicated that with decreasing levels of mitochondrial viscosity and increasing levels of ONOO-, the maximum of the emission wavelength of the probe shifted from 621 nm to 495 nm under 810 nm two-photon excitation. The baselines for the two emission peaks were significantly separated (Δλ = 126 nm), improving the resolution and reliability of bioimaging. Moreover, by ratiometric analysis during oxygen-glucose deprivation/reoxygenation (OGD/R, commonly used to simulate cell ischemia/reperfusion injury), the real-time visualization of the metabolic processes of autophagy and oxidative stress was possible. Our research indicated that during cellular oxygen-glucose deprivation/reoxygenation, cells produce ONOO-, causing cellular oxidative stress and cellular autophagy after 15 min, as such Mito-ONOO exhibits the potential for the monitoring and diagnosis of stroke, as well as providing insight into potential treatments, and drug design.

18.
Emerg Microbes Infect ; 11(1): 1435-1438, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35536092

RESUMO

Aspergillus luchuensis, an industrially important member of Aspergillus species belonging to section Nigri used in fermentation in East Asia, was isolated from an immunocompromised patient with probable invasive pulmonary aspergillosis who failed voriconazole therapy in China. This isolate showed non-wild-type susceptibility to itraconazole, voriconazole, isavuconazole, and posaconazole. A G1378A mutation in cyp51A, resulting in the G441S amino acid substitution, which is the homolog to G448S conferring triazole-resistance in A. fumigatus, was detected in the A. luchuensis isolate.


Assuntos
Aspergilose Pulmonar Invasiva , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergillus/genética , Aspergillus/metabolismo , Aspergillus fumigatus/genética , China , Farmacorresistência Fúngica/genética , Fermentação , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Testes de Sensibilidade Microbiana , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/metabolismo , Voriconazol/farmacologia , Voriconazol/uso terapêutico
19.
Anal Chem ; 94(15): 5797-5804, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35380428

RESUMO

Fluorescence imaging using probes with two-photon excitation and near-infrared emission is currently the most popular in situ method for monitoring biological species or events, with a large imaging depth, low background fluorescence, low optical damage, and high spatial and temporal resolution. Nevertheless, current fluorescent dyes with near-infrared emission still have some disadvantages such as poor water solubility, low fluorescence quantum yield, and small two-photon absorption cross sections. These drawbacks are mainly caused by the structural characteristics of dyes with large conjugation surfaces but lacking strong and rigid structures. Herein, a lysosome-targeted and viscosity-sensitive probe (NCIC-VIS) is designed and synthesized. The protonation of morpholine not only helps anchor NCIC-VIS to the lysosome but also significantly enhances its water solubility. More importantly, its viscosity can increase the rigid structure of NCIC-VIS, which will improve the fluorescence quantum yield and the two-photon absorption cross section due to the imposed restrictions on molecular torsion. Based on the abovementioned characteristics, the real-time imaging of cellular autophagy (could increase the viscosity of lysosomes) was realized using NCIC-VIS. The results demonstrated that the level of autophagy was significantly enhanced in mice during stroke, while the inhibition of oxidative stress significantly reduced the degree of autophagy. The study corroborates that oxidative stress induced by stroke can lead to the development of autophagy.


Assuntos
Lisossomos , Acidente Vascular Cerebral , Animais , Autofagia , Corantes Fluorescentes/química , Células HeLa , Humanos , Lisossomos/química , Camundongos , Imagem Óptica , Viscosidade , Água/análise
20.
Chem Sci ; 13(10): 2992-3001, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35382463

RESUMO

Ferroptosis is closely associated with cancer, neurodegenerative diseases and ischemia-reperfusion injury and the detection of its pathological process is very important for early disease diagnosis. Fluorescence based sensing technologies have become excellent tools due to the real-time detection of cellular physiological or pathological processes. However, to date the detection of ferroptosis using reducing substances as markers has not been achieved since the reducing substances are not only present at extremely low concentrations during ferroptosis but also play a key role in the further development of ferroptosis. Significantly, sensors for reducing substances usually consume reducing substances, instigating a redox imbalance, which further aggravates the progression of ferroptosis. In this work, a H2S triggered and H2S releasing near-infrared fluorescent probe (HL-H2S) was developed for the high-fidelity in situ imaging of ferroptosis. In the imaging process, HL-H2S consumes H2S and releases carbonyl sulfide, which is then catalyzed by carbonic anhydrase to produce H2S. Importantly, this strategy does not intensify ferroptosis since it avoids disruption of the redox homeostasis. Furthermore, using erastin as an inducer for ferroptosis, the observed trends for Fe2+, MDA, and GSH, indicate that the introduction of the HL-H2S probe does not exacerbate ferroptosis. In contrast, ferroptosis progression was significantly promoted when the release of H2S from HL-H2S was inhibited using AZ. These results indicate that the H2S triggered and H2S releasing fluorescent probe did not interfere with the progression of ferroptosis, thus enabling high-fidelity in situ imaging of ferroptosis.

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