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1.
J Mater Chem B ; 12(15): 3636-3658, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38529593

RESUMO

Cancer is a growing worldwide health problem with the most broadly studied treatments, in which immunotherapy has made notable advancements in recent years. However, innumerable patients have presented a poor response to immunotherapy and simultaneously experienced immune-related adverse events, with failed therapeutic results and increased mortality rates. Consequently, it is crucial to develop alternate tactics to boost therapeutic effects without producing negative side effects. Ultrasound is considered to possess significant therapeutic potential in the antitumor field because of its inherent characteristics, including cavitation, pyrolysis, and sonoporation. Herein, this timely review presents the comprehensive and systematic research progress of ultrasound-enhanced cancer immunotherapy, focusing on the various ultrasound-related mechanisms and strategies. Moreover, this review summarizes the design and application of current sonosensitizers based on sonodynamic therapy, with an attempt to provide guidance on new directions for future cancer therapy.


Assuntos
Neoplasias , Terapia por Ultrassom , Humanos , Terapia por Ultrassom/métodos , Ultrassonografia , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/patologia , Terapia Combinada , Imunoterapia
2.
BMC Public Health ; 23(1): 1209, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349685

RESUMO

OBJECTIVE: To analyze the risk factors associated with different levels of eye discomfort due to video terminal use among college students at different altitudes. METHODS: This cross-sectional study was conducted to assess the prevalence and extent of eye discomfort by distributing an questionnaire to university students via the Internet. To analyze the causes and risk factors of eye discomfort among college students at different altitudes after using video terminals. RESULTS: A total of 647 participants who met the criteria were included in this survey, of whom 292 (45.1%) were males and 355 (54.9%) were females. The results of the survey showed 194 (30.0%) participants without eye discomfort and 453 (70.0%) participants with eye discomfort. The results of the univariate comparison of the degree of eye discomfort in the study subjects with different characteristics showed that the differences in the degree of eye discomfort were statistically significant (P < 0.05) for the 7 groups of indicators: gender, region, wearing corneal contact lenses for more than 2 h per day, frequent use of eye drops, sleep time, total time of VDT use per day, and total time per VDT use, while the remaining indicators, including age, profession, and whether refractive surgery or other eye surgery was performed, whether frame glasses were worn for a long time, and duration of daily mask wear were not statistically significant. The results of multi-factor logistic analysis of the degree of eye discomfort in the study subjects with different characteristics showed that gender, region, frequent use of eye drops, sleep time, and total time of VDT use per day were the risk factors affecting the degree of eye discomfort. CONCLUSIONS: Female, high altitude, frequent use of eye drops, shorter daily sleep duration and longer daily VDT use were associated risk factors for the development of severe eye discomfort, where the severity of eye discomfort was significantly negatively correlated with increased sleep duration and significantly positively correlated with increased total time of VDT use.


Assuntos
Altitude , Lágrimas , Masculino , Humanos , Feminino , Estudos Transversais , Inquéritos e Questionários , Estudantes , Terminais de Computador
3.
Acta Pharm Sin B ; 13(4): 1686-1698, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37139408

RESUMO

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the ß-catenin level, and accordingly inhibit the Wnt/ß-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

4.
Kaohsiung J Med Sci ; 39(3): 221-233, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36524450

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver tumor, which seriously threatens human health. CircTNPO3 was up-regulated in HCC tissues. However, the regulatory mechanism of circTNPO3 in HCC was still unclear. We aimed to investigate the circTNPO3 function in the development of HCC. qRT-PCR and Western blot examined gene and protein levels. CCK8, EdU, flow cytometry, and Transwell assays were used to detect cell viability, proliferation, apoptosis, and invasion abilities. Dual-luciferase reporter and RIP assays determined the relationship between circTNPO3, miR-199b-5p, and striatin (STRN). The effect of CircTNPO3 on HCC progress was investigated in vivo. CircTNPO3 and STRN were significantly increased, while miR-199b-5p was repressed in HCC tissues or cells. Afterward, miR-199b-5p was negatively correlated with STRN. circTNPO3 was positively correlated with STRN. Knockdown of circTNPO3 inhibited cell viability, proliferation, invasion, and promoted apoptosis, while circTNPO3 overexpression had the opposite results. Furthermore, miR-199b-5p inhibition could eliminate the regulatory effect of sh-circTNPO3 on the proliferation and apoptosis in HCC cells. CircTNPO3 positively regulated STRN expression by targeting miR-199b-5p. MiR-199b-5p suppressed HCC progression by inhibiting STRN expression. Tumor formation in nude mice showed that knockdown of circTNPO3 significantly inhibited tumor growth and suppressed ki-67 levels. CircTNPO3 promoted HCC progression through regulating STRN expression by sponging miR-199b-5p, which provided a strategy for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Camundongos Nus , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteínas de Ligação a Calmodulina/genética , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo
5.
Cardiovasc Diagn Ther ; 12(5): 603-613, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36329963

RESUMO

Background: When patients with type A acute aortic dissection (TAAAD) present with changes to their ST-segment, diagnostic and treatment delays increase significantly. The performance of transthoracic echocardiography (TTE) screening of TAAAD in patients with ST-segment elevated myocardial infarction (STEMI) is yet to be validated. Methods: The diagnostic performance of TTE alone and combined with the aortic dissection risk score (ADRS) in TAAAD was evaluated. In this retrospective study (ChiCTR, No. 2000031291), TTE was reviewed to detect direct/indirect signs of TAAAD. The ADRS of each patient was calculated according to guidelines. Case adjudication was based on advanced imaging and surgery. Results: Among a total of 442 patients, TAAAD was diagnosed in 146 (33.0%). The presence of direct TTE signs had a sensitivity of 43.0% [95% confidence interval (CI): 35.0% to 52.0%] and specificity of 97.0% (95% CI: 95.0% to 99.0%), and the presence of any TTE sign had a sensitivity of 97.0% (95% CI: 93.0% to 99.0%) and specificity of 78.0% (95% CI: 73.0% to 82.0%) for TAAAD. The additive value of TTE was most evident in patients with low clinical probability for TAAAD (ADRS ≤1). The presence of ADRS ≤1 plus an absence of direct TTE signs for TAAAD rule-out had a sensitivity of 98.4% (95% CI: 96.1% to 99.6%). Conclusions: The use of TTE adds value in the screening of TAAAD in STEMI patients. In patients with low clinical probability for TAAAD, direct TTE signs can be used to rapidly identify those who require advanced imaging.

6.
Cancers (Basel) ; 14(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35892859

RESUMO

BACKGROUND: Breast cancer has one of highest morbidity and mortality rates for women. Abnormalities regarding epigenetics modification and pyruvate dehydrogenase kinase 1 (PDK1)-induced unusual metabolism contribute to breast cancer progression and chemotherapy resistance. However, the role and mechanism of epigenetic change in regulating PDK1 in breast cancer remains to be elucidated. METHODS: Gene set enrichment analysis (GSEA) and Pearson's correlation analysis were performed to analyze the relationship between histone deacetylase 2 (HDAC2), enhancer of zeste homologue 2 (EZH2), and PDK1 in database and human breast cancer tissues. Dual luciferase reporters were used to test the regulation between PDK1 and miR-148a. HDAC2 and EZH2 were found to regulate miR-148a expression through Western blotting assays, qRT-PCR and co-immunoprecipitation assays. The effects of PDK1 and miR-148a in breast cancer were investigated by immunofluorescence (IF) assay, Transwell assay and flow cytometry assay. The roles of miR-148a/PDK1 in tumor growth were investigated in vivo. RESULTS: We found that PDK1 expression was upregulated by epigenetic alterations mediated by HDAC2 and EZH2. At the post-transcriptional level, PDK1 was a new direct target of miR-148a and was upregulated in breast cancer cells due to miR-148a suppression. PDK1 overexpression partly reversed the biological function of miR-148a-including miR-148a's ability to increase cell sensitivity to Adriamycin (ADR) treatment-inhibiting cell glycolysis, invasion and epithelial-mesenchymal transition (EMT), and inducing apoptosis and repressing tumor growth. Furthermore, we identified a novel mechanism: DNMT1 directly bound to EZH2 and recruited EZH2 and HDAC2 complexes to the promoter region of miR-148a, leading to miR-148a downregulation. In breast cancer tissues, HDAC2 and EZH2 protein expression levels also were inversely correlated with levels of miR-148a expression. CONCLUSION: Our study found a new regulatory mechanism in which EZH2 and HDAC2 mediate PDK1 upregulation by silencing miR-148a expression to regulate cancer development and Adriamycin resistance. These new findings suggest that the HDAC2/EZH2/miR-148a/PDK1 axis is a novel mechanism for regulating cancer development and is a potentially promising target for therapeutic options in the future.

7.
BMC Med Educ ; 22(1): 378, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35581632

RESUMO

BACKGROUND: Gender bias in career choices has always been a matter of great concern, including in the field of medicine. This study reports on the current situation in this regard in China, including the reasons for Chinese medical students' willingness to engage in surgical careers; investigates their accounts of gender bias; and analyzes the effect of gender bias on their surgical career choices. METHODS: This study invited medical students from Harbin Medical University to fill out a non-mandatory questionnaire on whether they had witnessed gender bias, their surgical career intentions, and factors influencing their career intentions. A one-way analysis of variance was used to compare the differences between continuous variables. Pearson's chi-squared test was used to compare the differences between the categorical variables, the Kendall correlation coefficient (tau) was used to assess the correlation between the reasons rankings reported by gender, and a multiple regression analysis was conducted by logit model. RESULTS: A total of 643 students responded to the questionnaire. Of them, 63.76% expressed a willingness for a surgical career, with "interest" being a key driving factor (73.41%). Almost all respondents (96.27%) answered that there were more male leaders in the surgical departments they had rotated through or had contacted. Only a few respondents reported gender barriers influencing recruitment (32.19%). However, witnessing gender bias (recruitment of male required) was correlated to choice of surgical career (P < 0.05). Females were less willing to pursue a career in surgery if they had witnessed gender barriers in surgical recruitment. Male dominance also correlated to the choice of a surgical career (P < 0.1). Of the respondents, 53.19% believed that surgery was not suitable for females; among female respondents, this number was 56.12%, higher than for male respondents. When females think that the surgical profession is not suitable for them, it reduces the possibility of their pursuing a career in surgery. CONCLUSION: Most medical students were interested in surgical care. Witnessing gender bias decreases females' willingness to pursue a career in surgery. It is necessary to stimulate medical students' interest in surgery when formulating strategies to promote surgical career choices, as well as to reduce gender bias in surgery; in this way, females' surgical careers should be ensured.


Assuntos
Medicina , Especialidades Cirúrgicas , Estudantes de Medicina , Escolha da Profissão , Feminino , Humanos , Masculino , Sexismo , Inquéritos e Questionários
8.
Neurobiol Dis ; 170: 105749, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35568100

RESUMO

Increasing genetic and biochemical evidence has broadened our view of the pathomechanisms that lead to Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS), two fatal neurodegenerative diseases with similar symptoms and causes. Stress granules are dynamic cytosolic storage hubs for mRNAs in response to stress exposures, that are evolutionarily conserved cytoplasmic RNA granules in somatic cells. A lot of previous studies have shown that the impaired stress granules are crucial events in SMA/ALS pathogenesis. In this review, we described the key stress granules related RNA binding proteins (SMN, TDP-43, and FUS) involved in SMA/ALS, summarized the reported mutations in these RNA binding proteins involved in SMA/ALS pathogenesis, and discussed the mechanisms through which stress granules dynamics participate in the diseases. Meanwhile, we described the applications and limitation of current therapies targeting SMA/ALS. We futher proposed the promising targets on stress granules in the future therapeutic interventions of SMA/ALS.


Assuntos
Esclerose Lateral Amiotrófica , Atrofia Muscular Espinal , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/terapia , Humanos , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Atrofia Muscular Espinal/terapia , Mutação , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Grânulos de Estresse
9.
Biomater Sci ; 10(13): 3569-3574, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35635189

RESUMO

Programmable cancer therapies may perfectly prevent mutual drug restrictions, however, developing an efficient codelivery system with such an ability remains challenging. We herein first demonstrate the use of supramolecular-mediated dual-functional DNA nanocomposites for programmable chemodynamic therapy (CDT) and chemotherapy (CT), in which a water-soluble cyclodextrin-resveratrol (CD-Res) complex can be facilely encapsulated during the coassembly of Fe2+ and DNA to form the desired spherical nanocomposites. After endocytosis, the released Fe2+ can immediately trigger an endogenous Fenton reaction, inducing ferroptosis for CDT and ˙OH depletion, followed by the sustained release of the protected Res from the CD cavity. This process improves the efficacy of CT by preventing Res from the oxidation of ˙OH. The as-prepared nano-composites can sufficiently accumulate in the tumor, demonstrating an adequate programmable therapeutic performance without serious toxicity. Thus, a facile, fresh and changeable strategy for the design of antitumor therapies is presented.


Assuntos
Ferroptose , Nanocompostos , Neoplasias , Linhagem Celular Tumoral , DNA , Humanos , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico
10.
J Colloid Interface Sci ; 618: 68-77, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35334363

RESUMO

Near-infrared light-induced photothermal therapy (PTT) can achieve effective tumor ablation, but the associated hyperthermic temperatures result in off-target inflammatory damage to proximal tissues. Therefore, killing the tumor at a lower temperature is vital to improving the clinical effect of PTT. In this study, an Au-integrated Fe single-atom nanozyme (FeSAzyme) was developed through the immobilization of an ultrasmall Au nanozyme within a metal-organic framework via an in situ reduction approach. The nanozyme was found to exhibit favorable glucose oxidase- (GOD) like activity and photosensitizing properties to better achieve low-temperature PTT. The Au-carbon nanozyme was able to markedly inhibit tumor growth both in vitro and in vivo due to its GOD-like activity and enhanced photodynamic and photothermal properties. In addition, the integration of the Au nanozyme enhanced the FeSAzyme's peroxidase activity and catalyzed endogenous H2O2 species to generate reactive oxide species, thereby facilitating chemodynamic therapy. Furthermore, its integration markedly enhanced the PTT performance of the FeSAzyme, which achieved pronounced synergistic anti-tumor efficacy. The enzymatic activity and photothermal/photosensitive properties of the Au-FeSAzyme may help to overcome traditional therapeutic limitations, indicating its potential for catalytic cascade nanozymes in biomedical applications.


Assuntos
Ouro/química , Ferro/química , Neoplasias , Terapia Fototérmica , Biocatálise , Catálise , Linhagem Celular Tumoral , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico
11.
Int J Mol Sci ; 23(3)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35163707

RESUMO

Tyrosine kinase inhibitor (TKI) therapy has greatly improved lung cancer survival in patients with epidermal growth factor receptor (EGFR) mutations. However, the development of TKI-acquired resistance is the major problem to be overcome. In this study, we found that miR-196a expression was greatly induced in gefitinib-resistant lung cancer cells. To understand the role and mechanism of miR-196a in TKI resistance, we found that miR-196a-forced expression alone increased cell resistance to gefitinib treatment in vitro and in vivo by inducing cell proliferation and inhibiting cell apoptosis. We identified the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) bound to the promoter region of miR-196a and induced miR-196a expression at the transcriptional level. NRF2-forced expression also significantly increased expression levels of miR-196a, and was an upstream inducer of miR-196a to mediate gefitinib resistance. We also found that glycolipid transfer protein (GLTP) was a functional direct target of miR-196a, and downregulation of GLTP by miR-196a was responsible for gefitinib resistance. GLTP overexpression alone was sufficient to increase the sensitivity of lung cancer cells to gefitinib treatment. Our studies identified a new role and mechanism of NRF2/miR-196a/GLTP pathway in TKI resistance and lung tumor development, which may be used as a new biomarker (s) for TKI resistance or as a new therapeutic target in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Transporte/genética , Resistencia a Medicamentos Antineoplásicos , Gefitinibe/farmacologia , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Gefitinibe/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Chem Commun (Camb) ; 58(10): 1565-1568, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35014995

RESUMO

We develop for the first time a label-free fluorescent method for sensitive detection of fat mass and obesity-associated protein (FTO) activity using MazF-mediated primer generation rolling circle amplification. This method is very simple with ultrahigh sensitivity and good specificity, and it can detect FTO activity at the single-cell level. Moreover, this method can be applied for the measurement of kinetic parameters and the screening of FTO inhibitors.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/análise , DNA de Cadeia Simples/metabolismo , Técnicas de Amplificação de Ácido Nucleico/métodos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Linhagem Celular Tumoral , DNA de Cadeia Simples/química , Proteínas de Ligação a DNA/metabolismo , Endorribonucleases/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Limite de Detecção , Eletroforese em Gel de Poliacrilamida Nativa , Análise de Célula Única , Espectrometria de Fluorescência
13.
Cells ; 10(7)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209278

RESUMO

Development of resistance to therapy in ovarian cancer is a major hinderance for therapeutic efficacy; however, new mechanisms of the resistance remain to be elucidated. NADPH oxidase 4 (NOX4) is responsible for higher NADPH activity to increase reactive oxygen species (ROS) production. In this study, we showed that higher levels of NOX4 were detected in a large portion of human ovarian cancer samples. To understand the molecular mechanism of the NOX4 upregulation, we showed that NOX4 expression was induced by HIF-1α and growth factor such as IGF-1. Furthermore, our results indicated that NOX4 played a pivotal role in chemotherapy and radiotherapy resistance in ovarian cancer cells. We also demonstrated that NOX4 knockdown increased sensitivity of targeted therapy and radiotherapy through decreased expression of HER3 (ERBB3) and NF-κB p65. Taken together, we identified a new HIF-1α/NOX4 signal pathway which induced drug and radiation resistance in ovarian cancer. The finding may provide a new option to overcome the therapeutic resistance of ovarian cancer in the future.


Assuntos
Resistencia a Medicamentos Antineoplásicos , NADPH Oxidase 4/metabolismo , Neoplasias Ovarianas/metabolismo , Receptor ErbB-3/metabolismo , Transdução de Sinais , Afatinib/farmacologia , Processamento Alternativo/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Modelos Biológicos , NADPH Oxidase 4/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Intervalo Livre de Progressão , Fator de Transcrição RelA/metabolismo , Transcrição Gênica/efeitos dos fármacos , Trastuzumab/farmacologia
14.
Chem Sci ; 12(15): 5544-5554, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-34168791

RESUMO

Genomic oxidation and alkylation are two of the most important forms of cytotoxic damage that may induce mutagenesis, carcinogenicity, and teratogenicity. Human 8-oxoguanine (hOGG1) and alkyladenine DNA glycosylases (hAAG) are responsible for two major forms of oxidative and alkylative damage repair, and their aberrant activities may cause repair deficiencies that are associated with a variety of human diseases, including cancers. Due to their complicated catalytic pathways and hydrolysis mechanisms, simultaneous and accurate detection of multiple repair glycosylases has remained a great challenge. Herein, by taking advantage of unique features of T7-based transcription and the intrinsic superiorities of single-molecule imaging techniques, we demonstrate for the first time the development of a controlled T7 transcription-driven symmetric amplification cascade machinery for single-molecule detection of hOGG1 and hAAG. The presence of hOGG1 and hAAG can remove damaged 8-oxoG and deoxyinosine, respectively, from the dumbbell substrate, resulting in breaking of the dumbbell substrate, unfolding of two loops, and exposure of two T7 promoters simultaneously. The T7 promoters can activate symmetric transcription amplifications with the unfolded loops as the templates, inducing efficient transcription to produce two different single-stranded RNA transcripts (i.e., reporter probes 1 and 2). Reporter probes 1 and 2 hybridize with signal probes 1 and 2, respectively, to initiate duplex-specific nuclease-directed cyclic digestion of the signal probes, liberating large amounts of Cy3 and Cy5 fluorescent molecules. The released Cy3 and Cy5 molecules can be simply measured by total internal reflection fluorescence-based single-molecule detection, with the Cy3 signal indicating the presence of hOGG1 and the Cy5 signal indicating the presence of hAAG. This method exhibits good specificity and high sensitivity with a detection limit of 3.52 × 10-8 U µL-1 for hOGG1 and 3.55 × 10-7 U µL-1 for hAAG, and it can even quantify repair glycosylases at the single-cell level. Moreover, it can be applied for the measurement of kinetic parameters, the screening of potential inhibitors, and the detection of repair glycosylases in human serum, providing a new paradigm for repair enzyme-related biomedical research, drug discovery, and clinical diagnosis.

15.
Anal Chim Acta ; 1172: 338575, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119019

RESUMO

Highly selective, sensitive and fast gas sensing has attracted increasing attention in the fields of environmental protection, industrial production, personal safety as well as medical diagnostics. Field effect transistor (FET) sensors have been extensively investigated in gas sensing fields due to their small size, high sensitivity, high reliability and low energy consumption. This comprehensive review aims to discuss the recent advances in FET gas sensors based on materials such as carbon nanotubes, silicon carbide, silicon, metal oxides-, graphene-, transition metal dichalcogenides- and 2-dimensional black phosphorus. We first introduce different types of sensor structures and elaborate the gas-sensing mechanisms. Then, we describe the optimizing strategies for sensing performances, response parameters, FET based dual-mode sensors and FET based logic circuit sensors. Moreover, we present the key advances of the above materials in gas sensing performances. Meanwhile, shortcomings of such materials are also discussed and the future development of this field is proposed in this review.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33991956

RESUMO

An ultra-performance liquid chromatography tandem triple quadrupole compound linear ion trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed and validated for the detection of hypolipidemic drugs in fingerprints. 13 hypolipidemic drugs were well separated by the gradient elution of 0.01% formic acid in water and methanol at a flow rate of 0.4 mL/min within 11 min. The analytes were detected in positive (ESI+) and negative (ESI-) modes and scanned using scheduled multiple reaction monitoring-information dependent acquisition-enhanced product ion (SMRM-IDA-EPI) for best selectivity and sensitivity. The calibration curves showed good linearity in the range of 0.050-50.000 ng/patch with coefficients (r2) higher than 0.9904 for all analytes. Meantime, the LODs and LLOQs were in ranges of 0.001-0.034 and 0.003-0.050 ng/patch. The accuracies, intra-day and inter-day precision ranged from -13.3 to 0.3%, 1.1-10.4% and 3.7-14.5%, respectively. The recoveries ranged from 79.9 to 114.8%, while the absolute and relative matrix effects were in the range of 83.0-107.2% and 2.2-9.7%. By comparing the non-spiked fingerprints from healthy volunteers with the fingerprints obtained from patients, demonstrated that the method was competent for determination and quantitation of hypolipidemic drugs in fingerprints.


Assuntos
Medicina Legal/métodos , Hipolipemiantes/análise , Pele/química , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Limite de Detecção , Masculino , Espectrometria de Massas em Tandem , Adulto Jovem
17.
Talanta ; 224: 121918, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33379119

RESUMO

Sirtuin 1 (SIRT1) is an important histone deacetylase that regulates biological functions ranging from DNA repair to metabolism. The alteration of SIRT1 is associated with a variety of diseases including diabetes, inflammation, aging-related diseases, and cancers. Consequently, the detection of SIRT1 activity is of great therapeutic importance. Herein, we demonstrate for the first time the deacetylation-activated construction of single quantum dot (QD)-based nanosensor for sensitive SIRT1 assay. This nanosensor is composed of a Cy5-labeled peptide substrate and a streptavidin-coated QD. The peptide with one lysine acetyl group acts as both the Cy5 fluorophore carrier and the substrate for sensing SIRT1. In the presence of SIRT1, it removes the acetyl group in the acetylated peptide, and the resultant deacetylated peptide can react with the NHS-activated biotin reagent (sulfo-NHS-biotin) to form the biotinylated peptide. The multiple biotinylated peptides can assemble on single QD surface via biotin-streptavidin interaction, inducing efficient fluorescence resonance energy transfer (FRET) from the QD to Cy5, generating distinct Cy5 signal which can be simply quantified by total internal reflection fluorescence-based single-molecule detection. This single QD-based nanosensor can sensitively detect SIRT1 with a detection limit of as low as 3.91 pM, and it can be applied for the measurement of enzyme kinetic parameters and the screening of SIRT1 inhibitors. Moreover, this nanosensor can be used to detect the SIRT1 activity in cancer cells, providing a powerful platform for epigenetic research and SIRT1-targeted drug discovery.


Assuntos
Pontos Quânticos , Transferência Ressonante de Energia de Fluorescência , Nanotecnologia , Sirtuína 1 , Estreptavidina
18.
Cell Biol Toxicol ; 37(2): 277-291, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32472219

RESUMO

Uncoupling protein 1 (UCP1) has been implicated in ameliorating metabolic related disorders, of which most symptoms are risk factors for breast cancer. Here, we found that UCP1 was obviously downregulated in basal-like breast cancer (BLBC) and was positively correlated with improved survival. However, the underlying regulatory mechanisms remain largely unknown. Our studies showed that UCP1 inhibited tumor progression via suppressing aldehyde dehydrogenase (ALDH)-positive breast cancer stem cell (BCSC) population in BLBC. Furthermore, we found that UCP1 induced the upregulation of fructose bisphosphatase 1 (FBP1) which was previously blocked by Snail overexpression, and UCP1 decreased ALDH-positive BCSCs via FBP1-dependent metabolic rewiring, which could be reversed by Snail overexpression. In addition, breast cancer cells co-cultured with UCP1-deficient adipocytes had increased proportion of ALDH-positive BCSCs, indicating a potential protection role of UCP1 in tumor microenvironment. These results suggested that UCP1 suppressed BCSCs through inhibiting Snail-mediated repression of FBP1, and that upregulation of UCP1 might be a previously undescribed therapeutic strategy for combating breast cancer. Graphical abstract.


Assuntos
Aldeído Desidrogenase/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Fatores de Transcrição da Família Snail/metabolismo , Proteína Desacopladora 1/metabolismo , Adipócitos/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Frutose-Bifosfatase/metabolismo , Glicólise , Humanos , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Análise de Sobrevida , Proteína Desacopladora 1/deficiência , Regulação para Cima
19.
Chemosphere ; 263: 127802, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297000

RESUMO

Effective removal of cadmium (Cd) from Chlamys farreri by introducing ZnSO4, EDTA-Na2, and sodium citrate into seawater has previously been reported. However, some mechanisms underlying this removal are not clear. To address this lack of clarity, the present study aimed to investigate the changes of Cd forms in Chlamys farreri from treatment of these additives and analyze the physiological and biochemical responses by comparing the changes over treatment time in Catalase (CAT), Superoxide dismutase (SOD), and Glutathione s-transferase (GST) activity, as well as Malonaldehyde (MDA) concentration and glycogen level. Three forms of Cd, including protein -Cd, liberated Cd, and amino acid/peptide -Cd, were found, and they were sorted according to their Cd content into the following groups: protein -Cd > liberated Cd > amino acid/peptide-Cd. The removal rates of the three forms of Cd were 43.2%, 59.5%, and 59.0%, respectively, using ZnSO4 and EDTA-Na2. Additionally, a significant increase in Zn content was observed, which may suggest that reduction of bound Cd was partly due to the displacement of Cd by Zn. Moreover, Cd depuration using the additives can mitigate oxidative stress only in the first 12 h. Glycogen content continued to reduce over time, inferring that the healthy status of Chlamys farreri under treatment of the additives containing Zn can only be maintained within 12 h for excreting Cd when linking these physiological responses with the ability of the additives to remove Cd only in a short time, i.e. 12 h. The results indicated that Cd should be removed from Chlamys farreri for practical reasons.


Assuntos
Produtos Biológicos , Pectinidae , Animais , Cádmio , Ácido Edético , Estresse Oxidativo , Citrato de Sódio , Superóxido Dismutase/metabolismo
20.
Food Chem ; 343: 128475, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33168257

RESUMO

To solve the stability and oxidation issues of alpha-linolenic acid (ALA), this study focused on developing ALA nanoemulsion system (ALA-NE, oil-in-water) and evaluating the effect of environmental conditions on physical stability and the effect of antioxidants on oxidative stability. The physicochemical properties of nanoemulsions were measured at different conditions, including particle diameter, zeta potential, retention rate and peroxidation value (POV). The particle diameter increased significantly and the retention rate decreased after 25 days storage under the conditions of high temperature and metal ions. However, the influence of ionic strength, pH and light was insignificant. As an antioxidant, Vitamin E was more effective at retarding lipid oxidation of nanoemulsions than that of vitamin C. These results provided reference information in preparing effective and stable ALA-NE systems and enlarging the application fields.


Assuntos
Emulsões/química , Ácido alfa-Linolênico/química , Antioxidantes/química , Ácido Ascórbico/química , Armazenamento de Alimentos , Concentração de Íons de Hidrogênio , Luz , Nanoestruturas/química , Oxirredução , Tamanho da Partícula , Polissorbatos , Solubilidade , Temperatura , Vitamina E/química , Água/química
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