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1.
J Mol Histol ; 55(2): 187-199, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38478190

RESUMO

Polycystic ovary syndrome (PCOS) is an endocrine disease, and its pathogenesis and treatment are still unclear. Hexokinase domain component 1 (HKDC1) participates in regulating mitochondrial function and glycolysis. However, its role in PCOS development remains unrevealed. Here, female C57BL/6 mice were intraperitoneally injected with dehydroepiandrosterone (DHEA; 60 mg/kg body weight) to establish an in vivo model of PCOS. In vitro, KGN cells, a human ovarian granular cell line, were used to explore the potential mechanisms. DHEA-treated mice exhibited a disrupted estrus cycle, abnormal hormone levels, and insulin resistance. Dysfunction in mitochondria and glycolysis is the main reason for PCOS-related growth inhibition of ovarian granular cells. Here, we found that the structure of mitochondria was impaired, less ATP was generated and more mitochondrial Reactive Oxygen Species were produced in HKDC1-silenced KGN cells. Moreover, HKDC1 knockdown inhibited glucose consumption and decreased the production of glucose-6-phosphate and lactic acid. Conclusively, HKDC1 protects ovarian granulocyte cells from DHEA-related damage at least partly by preserving mitochondrial function and maintaining glycolysis.


Assuntos
Síndrome do Ovário Policístico , Feminino , Camundongos , Humanos , Animais , Síndrome do Ovário Policístico/metabolismo , Hexoquinase/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Desidroepiandrosterona/farmacologia , Desidroepiandrosterona/metabolismo , Granulócitos/metabolismo , Granulócitos/patologia
2.
J Dig Dis ; 24(12): 640-647, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38059890

RESUMO

Pyroptosis is an inflammasome-dependent form of programmed cell death that is mediated by caspases-1, -4, -5, and -11, and the gasdermin protein family. It is characterized by the rupture of cell membrane and the subsequent release of cell contents and interleukins, leading to inflammatory reaction and activation of the immune system. Recent studies have suggested that pyroptosis plays a role in the development of gastrointestinal tumors, impeding tumor generation and progression as well as providing a favorable microenvironment for tumor growth. In this review we outlined the current knowledge regarding the implications of pyroptosis in gastrointestinal cancers.


Assuntos
Neoplasias , Piroptose , Humanos , Caspases/metabolismo , Proteínas de Neoplasias/metabolismo , Trato Gastrointestinal , Microambiente Tumoral
3.
Immun Inflamm Dis ; 11(11): e1084, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38018601

RESUMO

BACKGROUND: Kimura disease (KD) is a rare chronic inflammatory disorder involving the Th2 pathway. Although medical treatment with steroids or other immunosuppressants is available, they may cause developmental issues in the pediatric population. Surgical intervention has also been suggested; however, it is associated with high recurrence rates. CASE PRESENTATION: A 14-year-old boy presented with left retroauricular lymph node enlargement at the age of 5 years. At the age of 7 years, he was diagnosed with nephrotic syndrome which subsided after steroid treatment for approximately 6 years. The retroauricular lymph node was surgically excised, and KD was confirmed. However, recurrent enlargement of the left retroauricular and neck lymph nodes occurred after 2 years. Persistently high IgE levels and fluctuating eosinophil counts were observed following steroid treatment. Dupilumab was prescribed because of the difficulty in tapering the steroid dosage. A loading dose of 600 mg was administered, followed by a maintenance dose of 300 mg every 2 weeks. The IgE level decreased after 3 months, and a low eosinophil count was maintained after steroid discontinuation. Follow-up computed tomography revealed a decrease in the size of the lymph nodes with no side effects such as conjunctivitis. CONCLUSION: Traditional treatments have raised developmental concerns in the pediatric population and are associated with high recurrence rates. Dupilumab targets the Th2 pathway and provides effective results, with few adverse effects. Dupilumab may be a therapeutic option for KD and other diseases involving the Th2 pathway.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia , Doença de Kimura , Masculino , Humanos , Criança , Pré-Escolar , Adolescente , Doença de Kimura/complicações , Doença de Kimura/tratamento farmacológico , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Hiperplasia Angiolinfoide com Eosinofilia/tratamento farmacológico , Hiperplasia Angiolinfoide com Eosinofilia/complicações , Esteroides/uso terapêutico , Imunoglobulina E
4.
Phytomedicine ; 117: 154912, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37295023

RESUMO

BACKGROUND: Therapeutic approaches based on glycolysis and energy metabolism of tumor cells are new promising strategies for the treatment of cancer. Currently, researches on the inhibition of pyruvate kinase M2, a key rate limiting enzyme in glycolysis, have been corroborated as an effective cancer therapy. Alkannin is a potent pyruvate kinase M2 inhibitor. However, its non-selective cytotoxicity has affected its subsequent clinical application. Thus, it needs to be structurally modified to develop novel derivatives with high selectivity. PURPOSE: Our study aimed to ameliorate the toxicity of alkannin through structural modification and elucidate the mechanism of the superior derivative 23 in lung cancer therapy. METHODS: On the basis of the principle of collocation, different amino acids and oxygen-containing heterocycles were introduced into the hydroxyl group of the alkannin side chain. We examined the cell viability of all derivatives on three tumor cells (HepG2, A549 and HCT116) and two normal cells (L02 and MDCK) by MTT assay. Besides, the effect of derivative 23 on the morphology of A549 cells as observed by Giemsa and DAPI staining, respectively. Flow cytometry was performed to assess the effects of derivative 23 on apoptosis and cell cycle arrest. To further assess the effect of derivative 23 on the Pyruvate kinase M2 in glycolysis, an enzyme activity assay and western blot assay were performed. Finally, in vivo the antitumor activity and safety of the derivative 23 were evaluated by using Lewis mouse lung cancer xenograft model. RESULTS: Twenty-three novel alkannin derivatives were designed and synthesized to improve the cytotoxicity selectivity. Among these derivatives, derivative 23 showed the highest cytotoxicity selectivity between cancer and normal cells. The anti-proliferative activity of derivative 23 on A549 cells (IC50 = 1.67 ± 0.34 µM) was 10-fold higher than L02 cells (IC50 = 16.77 ± 1.44 µM) and 5-fold higher than MDCK cells (IC50 = 9.23 ± 0.29 µM) respectively. Subsequently, fluorescent staining and flow cytometric analysis showed that derivative 23 was able to induce apoptosis of A549 cells and arrest the cell cycle in the G0/G1 phase. In addition, the mechanistic studies suggested derivative 23 was an inhibitor of pyruvate kinase; it could regulate glycolysis by inhibiting the activation of the phosphorylation of PKM2/STAT3 signaling pathway. Furthermore, studies in vivo demonstrated derivative 23 significantly inhibited the growth of xenograft tumor. CONCLUSION: In this study, alkannin selectivity is reported to be significantly improved following structural modification, and derivative 23 is first shown to be able to inhibit lung cancer growth via the PKM2/STAT3 phosphorylation signaling pathway in vitro, indicating the potential value of derivative 23 in treating lung cancer.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Naftoquinonas , Humanos , Camundongos , Animais , Piruvato Quinase/metabolismo , Linhagem Celular Tumoral , Naftoquinonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Apoptose , Proliferação de Células , Antineoplásicos/farmacologia , Antineoplásicos/química
6.
Zhongguo Zhong Yao Za Zhi ; 48(2): 382-389, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725228

RESUMO

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), ß-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.


Assuntos
Medicamentos de Ervas Chinesas , Ginsenosídeos , Pós , Benchmarking , Medicamentos de Ervas Chinesas/química , Sacarose , Cromatografia Líquida de Alta Pressão/métodos
7.
Cancer Med ; 12(4): 4981-4992, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36043478

RESUMO

BACKGROUND: The current study aimed to investigate the dynamic alteration and prognostic significance of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 status of immune cells in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC). METHODS: Multiplex immunofluorescence staining was performed to examine CD68+ TAM, CD4+ T cell, CD8+ T cell, FOXP3+ Treg cell, and PD-L1 expression in paired MIBC tissues (n = 54) before and after NAC. Patients were then divided into definite responders (DR), (≤pT1) and incomplete responders (IR). RESULTS: There was no significant difference between DR and IR cohorts for the immune cell infiltration levels at the baseline status. Tobacco history was identified to be associated with worse NAC efficacy. CD68+ (stroma area: p = 0.025; tumor area: p = 0.028; total area: p = 0.013) and CD68+ PD-L1- (stroma area: p = 0.035; tumor area: p = 0.013 total area: p = 0.014) TAMs infiltration levels decreased significantly after NAC, while there was no significant difference of CD68+ PD-L1+ and TILs. The infiltration of CD68+ (p = 0.033), CD68+ PD-L1- (p = 0.033), and CD68+ PD-L1+ (p < 0.001) TAMs in stroma area were significantly associated with poorer disease-free survival rate (DFS) of MIBC patients. CONCLUSION: CD68+ and CD68+ PD-L1- TAMs infiltration levels decreased significantly after NAC and pre-treatment TAM infiltration levels were independent prognostic factors for MIBC patients. While there was no sufficient evidence demonstrating that pre-treatment TILs or TAMs could predict response to NAC in MIBC patients.


Assuntos
Terapia Neoadjuvante , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Antígeno B7-H1/metabolismo , Neoplasias da Bexiga Urinária/patologia , Macrófagos , Músculos/metabolismo , Linfócitos do Interstício Tumoral , Microambiente Tumoral
8.
Comput Math Methods Med ; 2022: 2382458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991134

RESUMO

This work is aimed at exploring the nursing strategies and effects of continuous renal replacement therapy (CRRT) for end-stage renal disease (ESRD) with refractory hypotension under the background of smart health. 40 ESRD patients with refractory hypotension who received CRRT treatment were enrolled as the research objects and were randomly rolled into the intervention group and the control group, with 20 cases in each group. Patients in the control group received routine nursing, and those in the intervention group received individualized nursing. The incidence of hypotension, dry body weight, serous cavity effusion, renal function indicators (blood urea nitrogen (BUN) and creatinine (Cre)), and patient satisfaction were compared between the two groups. The results showed that the probability of hypotension in the intervention group was 9.38%, which was lower than that in the control group (34.38%). The probability of early termination of dialysis in the intervention group was 0%, which was lower than that in the control group (18.75%), and the difference was statistically significant (P < 0.05). The decreases of BUN and Cre in the intervention group were significantly greater than those in the control group, and the differences were statistically significant (P < 0.05). The proportion of water growth less than 10% during dialysis in the intervention group was 98.44%, which was greater than that in the control group (93.45%), and the difference was statistically significant (P < 0.05). The ultrafiltration volume after dialysis in the intervention group was 2850 ± 400 mL, which was greater than that in the control group 2350 ± 350 mL. After intervention, the proportion of patients with pleural effusion in the intervention group was 10% less than that in the control group (20%), and the difference was statistically significant (P < 0.05). The satisfaction rate of the intervention group was 97.66%, which was higher than that of the control group (65.63%). In conclusion, individualized nursing was more helpful to the recovery of ESRD patients with refractory hypotension treated with CRRT than routine nursing.


Assuntos
Injúria Renal Aguda , Hipotensão , Falência Renal Crônica , Humanos , Hipotensão/etiologia , Rim/fisiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Terapia de Substituição Renal/métodos
9.
Front Oncol ; 12: 816444, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494010

RESUMO

Muscle-invasive bladder cancer (MIBC) is an aggressive disease requiring active management. Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is considered the standard treatment paradigm for MIBC patients, which could result in significant perioperative mortality and morbidity, as well as the significant alteration of the quality of life (QOL). Notably, multimodal bladder-preserving treatment strategies have been recommended for highly selected patients. Pathologic complete response (pCR) after NAC is a powerful prognostic indicator of survival for patients with MIBC. Clinical complete response (cCR) is then introduced as a complementary endpoint for pCR to assess disease status preoperatively. Bladder preservation strategy for patients who achieve cCR following NAC is emerging as a new treatment concept. However, the efficiency of the conservative strategy remains controversial. In this state-of-the-art review, we discuss the advantages and limitations of cCR and the feasibility and safety of bladder preservation strategy in highly selected MIBC patients who achieve cCR following NAC. We conclude that a conservative strategy can be considered a reasonable alternative to RC in carefully selected cCR MIBC patients, leading to acceptable oncological outcomes.

10.
PeerJ ; 9: e12315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754620

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is an inflammation-associated tumor involved in immune tolerance and evasion in the immune microenvironment. Heat shock proteins (HSPs) are involved in the occurrence, progression, and immune regulation of tumors. Therefore, HSPs have been considered potential therapeutic targets. Here, we aimed to elucidate the value of HSP family A (Hsp70) member 4 (HSPA4) in the diagnosis and predicting prognosis of HCC, and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints. Gene mutation, DNA methylation, and the pathway involved in HCC were also analyzed. METHODS: The gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to compare HSPA4 expression, and the results were confirmed by immunohistochemical staining of clinical samples. R package was used to analyze the correlation between HSPA4 and cancer stage, and to establish receiver operating characteristic (ROC) curve of diagnosis, time-dependent survival ROC curve, and a nomogram model. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation, and their effect on prognosis. The Tumor Immune Estimation Resource (TIMER) was used to analyze immune cell infiltration, immune cell biomarkers, and immune checkpoints. The STRING database was used to analyze protein-protein interaction network information. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functions of HSPA4 and its functional partner genes. RESULTS: Overexpression of HSPA4 was identified in 25 cancers. Overexpression of HSPA4 considerably correlated with cancer stage and alpha-fetoprotein (AFP) level in HCC. Patients with higher HSPA4 expression showed poorer prognosis. HSPA4 expression can accurately identify tumor from normal tissue (AUC = 0.957). The area under 1-, 3-, and 5-year survival ROCs were above 0.6. The HSPA4 genetic alteration rate was 1.3%. Among the 14 DNA methylation CpG sites, seven were related to the prognosis of HCC. HSPA4 was positively related to immune cell infiltration and immune checkpoints (PD-1 and CTLA-4) in HCC. The KEGG pathway enrichment analysis revealed HSPA4 enrichment in antigen processing and presentation together with HSPA8 and HSP90AA1. We verified the value of HSPA4 in the diagnosis and predicting prognosis of HCC. HSPA4 may not only participate in the occurrence and progression but also the immune regulation of HCC. Therefore, HSPA4 can be a potential diagnostic and prognostic biomarker and a therapeutic target for HCC.

11.
Pediatr Rep ; 13(2): 162-167, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916031

RESUMO

Herpes zoster is a relatively rare infectious disease in the pediatric population, as compared with adults, which is due to the reactivation of latent Varicella-Zoster virus. We report a 7-year-old child without any history of varicella, who first experienced skin pain and later presented skin lesions in dermatomal distribution. Finally, the patient was diagnosed with herpes zoster. We aim to emphasize that herpes zoster could occur in immunocompetent children and may be due to the reactivation of the vaccine strain or previous subclinical infection.

12.
Mikrochim Acta ; 187(5): 282, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32318822

RESUMO

A sandwich-type fluorescent biosensor for the determination of tumor-related exosome was designed. It is based on magnetic nanoparticle (MNP) capture and horseradish peroxidase (HRP) catalysis. MNPs were used as the substrate to capture exosomes by modifying the CD63 antibody on MNPs surface. After that, the biotinylated epithelial cell adhesion molecule (EpCAM) antibody was used to capture the tumor-related exosomes, which specifically express EpCAM. A novel method for the fluorescence measurement of tumor-associated exosome was achieved, with a detection limit as low as 200 (± 9) particles mL-1. The analytical range of this method is from 576 (± 15) particles mL-1 to 5.76 × 107 (± 5.1 × 105) particles mL-1. For the fluorescence measurement, the excitation wavelength was set to 320 nm. Fluorescent spectra were collected at emission wavelength in the range 370 to 550 nm; the data shown in the calibration plot were studied by using the fluorescence intensity at 406 nm. This sensor was also able to successfully detect the exosomes from the plasma of patients with hepatocellular carcinoma (HCC) and healthy humans. Graphical abstract Schematic representation of the sensing process of immunoassay-type biosensor based on magnetic nanoparticle capture and the fluorescence signal formed by the horseradish peroxidase (HRP) catalysis for tumor-related exosome determination.


Assuntos
Técnicas Biossensoriais , Carcinoma Hepatocelular/sangue , Exossomos/química , Fluorescência , Peroxidase do Rábano Silvestre/metabolismo , Imunoensaio , Neoplasias Hepáticas/sangue , Biocatálise , Calibragem , Carcinoma Hepatocelular/diagnóstico , Exossomos/metabolismo , Células Hep G2 , Peroxidase do Rábano Silvestre/química , Humanos , Neoplasias Hepáticas/diagnóstico , Nanopartículas de Magnetita/química , Tamanho da Partícula , Espectrometria de Fluorescência , Propriedades de Superfície , Células Tumorais Cultivadas
13.
Anal Chem ; 92(9): 6719-6726, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32271544

RESUMO

Mapping the complete molecular composition of a lipidome is considered an important goal of lipidomics for unraveling pathways and mechanisms behind lipid homeostasis. Conventional dissociation methods of mass spectrometry (MS) usually cannot give detailed structural information on lipids such as locations of carbon-carbon double bonds (C═C) in acyl chains. Double-bond derivatization via the Paternò-Büchi (PB) reaction has been demonstrated as a simple and highly efficient method for identification of C═C locations of different classes of lipids when paired with tandem mass spectrometry (MS/MS). In this work, reversed-phase lipid chromatography (RPLC)-MS was coupled with an online PB reaction to achieve enhanced analysis of isomers and isobars of phospholipids. A new acetone-containing mobile phase was developed that showed good elution performance for the separation of phospholipids by C18 columns. An improved flow microreactor was developed, enabling online derivatization of phospholipid C═C in 20 s. The workflow of RPLC-PB-MS/MS was developed and optimized for identification of C═C locations in isobaric ether-linked and diacyl phospholipids, 13C isobars, and acyl chain isomers in biological lipid extracts. Separation and identification of C═C locations of cis/trans phospholipid isomers were achieved for lipid standards. The incorporation of the PB reaction into the RPLC-MS workflow enabled analysis of phospholipid isomers and isobars with high confidence, demonstrating its potential for high-throughput phospholipid identification from complex mixtures.


Assuntos
Fosfolipídeos/análise , Cromatografia de Fase Reversa , Espectrometria de Massas , Estrutura Molecular , Processos Fotoquímicos , Estereoisomerismo
14.
Acta Anatomica Sinica ; (6): 139-149, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-844566

RESUMO

In the past decade, in addition to using traditional naked-eye morphological analysis, two-dimensional measurement and data comparison, more and more scholars placed great emphasis on the application of new technologies available and supported the study of ancient human remains from a multi-disciplinary perspective. Through outlining recent advances in the application of new techniques on research of ancient human remains, this paper briefly summarized the characteristics of present research and gave an outlook on future research of ancient human remains in China.

15.
Mol Cancer ; 18(1): 138, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526370

RESUMO

Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMT-related circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.


Assuntos
Transformação Celular Neoplásica/genética , Transição Epitelial-Mesenquimal/genética , Predisposição Genética para Doença , RNA Circular , Animais , Biomarcadores Tumorais , Transformação Celular Neoplásica/metabolismo , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Transdução de Sinais , Transcrição Gênica
16.
Bioelectrochemistry ; 129: 278-285, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254805

RESUMO

A novel electrochemical magnetoimmunosensor for the rapid and sensitive detection of carcinoembryonic antigen (CEA) was fabricated based on a combination of high-efficiency immunomagnetic separation, bifunctional Au-nanoparticle (bi-AuNP) probes, and enzyme catalytic amplification. The reaction carrier magnetic beads (MBs) effectively reduced the toxicity of the complex sample to the working electrode, and the signal carrier bi-AuNP probes loaded a large amount of signal molecules, both of which enhanced the signal-to-noise ratio and further improved the detection sensitivity. A detection limit as low as 0.11 pg/mL was achieved for CEA detection based on the immunomagnetic separation and bi-AuNP probe-based multiamplification strategy, and the strategy was further successfully applied in human serum samples. The transducer was regenerated via a simple washing procedure, which enabled the detection of all samples on a single electrode with high reproducibility. The proposed strategy, which has the merits of high sensitivity, selectivity, and reproducibility exhibits great potential for detection in complex samples.


Assuntos
Anticorpos Imobilizados/química , Técnicas Biossensoriais/métodos , Antígeno Carcinoembrionário/sangue , Ouro/química , Imãs/química , Nanopartículas Metálicas/química , Técnicas Eletroquímicas/métodos , Humanos , Imunoensaio/métodos , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura , Reprodutibilidade dos Testes
17.
Mikrochim Acta ; 186(6): 388, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147793

RESUMO

An electrochemical aptasensing method is described for the determination of the biomarker CA125. It combines aptamer recognition and target-triggered strand displacement amplification. Flower like gold nanostructures were electrodeposited on a screen-printed carbon electrode to increase the sensor surface, to assemble more toehold-containing hairpin probe 1 (Hp1), and to improve the accessibility for DNA strands. Under the optimal conditions, this assay has a linear response in the 0.05 to 50 ng•mL-1 CA125 concentration range, with a low detection limit of 5.0 pg•mL-1. This method is specific and stable. It was successfully applied to the detection of CA125 in spiked biological samples, with recoveries between 82.5% and 104.1%. Graphical abstract.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Antígeno Ca-125/análise , Técnicas Eletroquímicas/métodos , Proteínas de Membrana/análise , Nanopartículas Metálicas/química , Aptâmeros de Nucleotídeos/genética , Antígeno Ca-125/sangue , Antígeno Ca-125/urina , Carbono/química , DNA/química , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Proteínas de Membrana/sangue , Proteínas de Membrana/urina , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico , Saliva/química
18.
Ann Clin Lab Sci ; 49(2): 183-188, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31028062

RESUMO

BACKGROUND: Pizotifen, a 5-HT2A receptor antagonist is usually considered as a preventative drug to reduce the frequency of recurrent migraine headaches in previous research. But it is not clear whether Pizotifen exerts therapeutic effect in colon cancer. The objective of this study was to investigate the effect of Pizotifen on the proliferation and migration of colon cancer HCT116 cells. METHODS: We performed cell counting kit-8 (CCK8) assay to evaluate the effects of Pizotifen on HCT116 cells proliferation, and transwell migration and invasion assays to assess cell motility. Then, flow cytometry apoptosis assay was used to evaluate the effect of Pizotifen on cell apoptosis. Finally, western blot assay was used to determine the changes of Wnt signaling pathway related proteins in HCT116 cells after Pizotifen treatment. RESULTS: The results showed that Pizotifen could significantly inhibit HCT116 cells proliferation, migration, and invasion. The results of flow cytometry apoptosis assay demonstrated that Pizotifen could promote the apoptosis of HCT116 cells. The expression of Wnt3a and ß-Catenin protein were significantly inhibited, while the expression of E-cadherin was significantly up-regulated in Pizotifen treated HCT116 cells. CONCLUSION: Pizotifen may inhibit HCT116 cells proliferation and migration by suppressing Wnt signaling pathway and it may serve as a potential candidate drug for the treatment of colon cancer in the future.


Assuntos
Movimento Celular/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação para Baixo/efeitos dos fármacos , Pizotilina/farmacologia , Via de Sinalização Wnt/genética , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células HCT116 , Humanos , Invasividade Neoplásica , Via de Sinalização Wnt/efeitos dos fármacos
19.
Mikrochim Acta ; 185(3): 202, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29594643

RESUMO

An amperometric aptasensor is reported for the electrochemical determination of the epithelial cell adhesion molecule (EpCAM). It is based on a combination of EpCAM-driven toehold-mediated DNA recycling amplification, the specific recognition of EpCAM aptamer, and its binding to EpCAM. Hairpin probe 1 (Hp1) with a toehold region was modified with a 5'-thiol group (5'-SH) and self-assembled onto the surface of a gold electrode. Upon addition of EpCAM, the probe A (a 15-mer) is liberated from the aptamer/probe A complex and then hybridizes with the toehold domain of Hp1. This results in the exposure of another toehold for further hybridizing with hairpin probe 2 (Hp2) to displace probe A in the presence of Hp2 that was labeled with the electrochemical probe Methylene Blue (MB). Subsequently, liberated probe A is hybridized again with another Hp1 to start the next round of DNA recycling amplification by reusing probe A. This leads to the formation of plenty of MB-labeled DNA strands on the electrode surface and generates an amplified current. This 1:N probe-response amplification results in ultrasensitive and specific detection of EpCAM, with a 20 pg·mL-1 detection limit. The electrode is highly stable and regenerable. It was successfully applied to the determination of EpCAM in spiked human serum, urine and saliva, and thus provides a promising tool for early clinical diagnosis. Graphical abstract Schematic illustration of the electrochemical detection for EpCAM. The method is based on aptamer-based recognition and EpCAM-driven toehold-mediated DNA recycling amplification. Hp1: Hairpin probe 1; Hp2: Hairpin probe 2; MB: Methylene blue; MCH: 6-Mercapto-1-hexanol; EpCAM: Epithelial cell adhesion molecule.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , DNA/química , Molécula de Adesão da Célula Epitelial/análise , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Eletroquímica , Molécula de Adesão da Célula Epitelial/metabolismo , Estudos de Viabilidade , Ouro/química , Humanos
20.
Radiat Prot Dosimetry ; 178(4): 354-358, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28981892

RESUMO

222Rn concentrations in underground drinking water samples in 12 cities from seven provinces (municipalities), China were determined by using a continuous radon monitor with air-water exchanger. A total of 73 underground water samples were collected. The observed radon levels were in a range of 1.0-63.8 Bq l-1, with a mean of 11.8 Bq l-1. The annual effective dose from inhalation of water-borne radon for average radon content in underground water was 72.6 µSv and for maximal observed radon concentration in underground water the corresponding dose was 393.8 µSv. The dose contribution of inhalation dose from water-borne radon should be paid attention in some granitic area.


Assuntos
Água Potável/análise , Água Subterrânea/análise , Monitoramento de Radiação/métodos , Radônio/análise , Poluentes Radioativos da Água/análise , China , Cidades , Sedimentos Geológicos
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