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2.
Biomed Opt Express ; 15(1): 14-27, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38223175

RESUMO

Urea and lactate are biomarkers in sweat that is closely associated with human health. This study introduces portable, rapid, sensitive, stable, and high-throughput wearable sweat biosensors utilizing Au-Ag nanoshuttles (Au-Ag NSs) for the simultaneous detection of sweat urea and lactate. The Au-Ag NSs arrays within the biosensor's microfluidic cavity provide a substantial surface-enhanced Raman scattering (SERS) enhancement effect. The limit of detection (LOD) for urea and lactate are 2.35 × 10-6 and 8.66 × 10-7 mol/L, respectively. This wearable sweat biosensor demonstrates high resistance to compression bending, repeatability, and stability and can be securely attached to various body parts. Real-time sweat analysis of volunteers wearing the biosensors during exercise demonstrated the method's practicality. This wearable sweat biosensor holds significant potential for monitoring sweat dynamics and serves as a valuable tool for assessing bioinformation in sweat.

3.
Talanta ; 270: 125563, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38134815

RESUMO

Colorectal cancer (CRC) remains a significant contributor to the global mortality rate, and a single biomarker cannot meet the specificity required for CRC screening. To this end, we developed a multiplexed, pump-free surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) using a one-step recognition release mechanism; the aptamer-functionalized novel Au nanocrown array (AuNCA) was used as the detection element embedded in the detection zone of the platform for rapid and specific detection of protein markers in multiple samples simultaneously. Here, the corresponding aptamer specifically captured the protein marker, causing the complementary strand of the aptamer carrying the Raman signal molecule to be shed, reducing the SERS signal. Based on this platform, sensitive and specific detection of the target can be accomplished within 15 min with detection limits of 0.031 pg/mL (hnRNP A1) and 0.057 pg/mL (S100P). Meanwhile, the platform was consistent with ELISA results when used to test clinical. By substituting different aptamers, this platform can provide a new solution for the rapid and sensitive detection of protein markers, which has promising applications in future disease detection.


Assuntos
Aptâmeros de Nucleotídeos , Nanopartículas Metálicas , Neoplasias , Biomarcadores Tumorais , Proteínas , Análise Espectral Raman/métodos , Ouro , Limite de Detecção
4.
Parasit Vectors ; 16(1): 450, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066526

RESUMO

BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model. METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by flow cytometry, and the levels of cytokines in cell supernatants or in sera of mice were measured (ELISA). The therapeutic effect of EgCF on sepsis was evaluated by observing the survival rates of mice for 72 h after CLP, and the pathological injury to the liver, kidney, and lung was measured under a microscope. The expression of TLR-2/MyD88 in tissues was measured by western blot to determine whether TLR-2/MyD88 is involved in the sepsis-induced inflammatory signaling pathway. RESULTS: In vitro culture with BMDMs showed that EgCF promoted macrophage polarization to M2 type and inhibited lipopolysaccharide (LPS)-induced M1 macrophages. EgCF treatment provided significant therapeutic effects on CLP-induced sepsis in mice, with increased survival rates and alleviation of tissue injury. The EgCF conferred therapeutic efficacy was associated with upregulated anti-inflammatory cytokines (IL-10 and TGF-ß) and reduced pro-inflammatory cytokines (TNF-α and INF-γ). Treatment with EgCF induced Arg-1-expressed M2, and inhibited iNOS-expressed M1 macrophages. The expression of TLR-2 and MyD88 in EgCF-treated mice was reduced. CONCLUSIONS: The results demonstrated that EgCF confers a therapeutic effect on sepsis by inhibiting the production of pro-inflammatory cytokines and inducing regulatory cytokines. The anti-inflammatory effect of EgCF is carried out possibly through inducing macrophage polarization from pro-inflammatory M1 to regulatory M2 phenotype to reduce excessive inflammation of sepsis and subsequent multi-organ damage. The role of EgCF in regulating macrophage polarization may be achieved by inhibiting the TLR2/MyD88 signaling pathway.


Assuntos
Echinococcus granulosus , Sepse , Camundongos , Animais , Echinococcus granulosus/metabolismo , Líquido Cístico/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Sepse/tratamento farmacológico , Inflamação/tratamento farmacológico , Anti-Inflamatórios , Lipopolissacarídeos
7.
Int J Nanomedicine ; 18: 3429-3442, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37383221

RESUMO

Introduction: As the most common malignant tumor in the world, the prognosis of patients with advanced lung cancer remains poor even after treatment. There are many prognostic marker assays available, but there is still more room for the development of high-throughput and sensitive detection of circulating tumor DNA (ctDNA). Surface-enhanced Raman spectroscopy (SERS), a spectroscopic detection method that has received wide attention in recent years, can achieve exponential amplification of Raman signals by using different metallic nanomaterials. Integrating SERS with signal amplification strategy into the microfluidic chip and applying it to ctDNA detection is expected to be an effective tool for the prognosis of lung cancer treatment effect in the future. Methods: To construct a high-throughput SERS microfluidic chip integrated with enzyme-assisted signal amplification (EASA) and catalytic hairpin self-assembly (CHA) signal amplification strategies, using hpDNA-functionalized Au nanocone arrays (AuNCAs) as capture substrates and cisplatin-treated lung cancer mice to simulate the detection environment for sensitive detection of ctDNA in serum of lung cancer patients after treatment. Results: The SERS microfluidic chip constructed by this scheme, with two reaction zones, can simultaneously and sensitively detect the concentrations of four prognostic ctDNAs in the serum of three lung cancer patients with a limit of detection (LOD) as low as the aM level. The results of the ELISA assay are consistent with this scheme, and its accuracy is guaranteed. Conclusion: This high-throughput SERS microfluidic chip has high sensitivity and specificity in the detection of ctDNA. This could be a potential tool for prognostic assessment of lung cancer treatment efficacy in future clinical applications.


Assuntos
Neoplasias Pulmonares , Microfluídica , Animais , Camundongos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Análise Espectral Raman , Modelos Animais de Doenças , Ouro
8.
Int J Nanomedicine ; 18: 2553-2565, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213349

RESUMO

Purpose: This paper aims to construct a surface-enhanced Raman spectroscopy (SERS) biosensor based on functionalized Au-Si nanocone arrays (Au-SiNCA) using a dual signal amplification strategy (SDA-CHA) to evaluate telomerase activity during epithelial-mesenchymal transition (EMT) in laryngeal carcinoma (LC). Methods: A SERS biosensor based on functionalized Au-SiNCA was designed with an integrated dual-signal amplification strategy to achieve ultrasensitive detection of telomerase activity during EMT in LC patients. Results: Labeled probes (Au-AgNRs@4-MBA@H1) and capture substrates (Au-SiNCA@H2) were prepared by modifying hairpin DNA and Raman signal molecules. Using this scheme, telomerase activity in peripheral mononuclear cells (PMNC) could be successfully detected with a limit of detection (LOD) as low as 10-6 IU/mL. In addition, biological experiments using BLM treatment of TU686 effectively mimicked the EMT process. The results of this scheme were highly consistent with the ELISA scheme, confirming its accuracy. Conclusion: This scheme provides a reproducible, selective, and ultrasensitive assay for telomerase activity, which is expected to be a potential tool for the early screening of LC in future clinical applications.


Assuntos
Técnicas Biossensoriais , Carcinoma , Nanopartículas Metálicas , Telomerase , Humanos , Transição Epitelial-Mesenquimal , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Técnicas Biossensoriais/métodos , Limite de Detecção , Ouro/química
9.
Anal Chim Acta ; 1236: 340574, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36396230

RESUMO

Early and precise diagnosis of lung cancer is critical for a better prognosis. However, it is still a challenge to develop an effective strategy for early precisely diagnose and effective treatments. Here, we designed a label-free and highly accurate classification serum analytical platform for identifying mice with lung cancer. Specifically, the microarray chip integrated with Au nanostars (AuNSs) array was employed to measure the surface-enhanced Raman scattering (SERS) spectra of serum of tumor-bearing mice at different stages, and then a recognition model of SERS spectra was constructed using the principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) algorithm. The microarray chip can realize rapid, sensitive, and high-throughput detection of SERS spectra of serum. RCKNCN based on the PCA-generated features successfully differentiated the SERS spectra of serum of tumor-bearing mice at different stages with a classification accuracy of 100%. The most prominent spectral features for distinguishing different stages were captured in PCs loading plots. This work not only provides a practical SERS chip for the application of SERS technology in cancer screening, but also provides a new idea for analyzing the feature of serum at the spectral level.


Assuntos
Neoplasias Pulmonares , Análise Espectral Raman , Camundongos , Animais , Análise Espectral Raman/métodos , Análise de Componente Principal , Neoplasias Pulmonares/diagnóstico , Análise por Conglomerados , Detecção Precoce de Câncer
10.
J Mater Chem B ; 10(43): 8931-8944, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36268643

RESUMO

In this study, we apply catalytic hairpin assembly (CHA) as the signal amplification strategy for the quantification of carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA21-1) with a surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) as the carrier. Herein, antibody-DNA conjugates are designed to assist the application of CHA amplification in protein detection. In the presence of protein biomarkers, antibody-DNA conjugates can specifically bind to the target proteins, forming the antigen@antibody-DNA conjugates. The terminal free part of the DNA on the conjugates can trigger the CHA events to connect SERS nanotags to capture nanoprobes. Then, micro-magnet can gather the CHA products in a rectangular chamber, resulting in the aggregation of SERS nanotags, which can ultimately generate abundant "hot spots" for SERS signal enhancement. Using this strategy, CEA and CYFRA21-1 can be successfully determined with a limit of detection (LOD) as low as pg mL-1, much lower than recently reported methods. Meanwhile, a non-small cell lung cancer (NSCLC)-xenografted mouse model was established, and SERS was applied to analyze the expression level of CEA and CYFRA21-1 in tumorigenesis and development. The comparison between SERS results and those of the ELISA method demonstrated a high degree of consistency, suggesting that the proposed CHA-assisted LoC-SERS device has satisfying accuracy. Thus, introducing the CHA strategy via the design of antibody-DNA conjugates opens new gates to ultra-sensitive and specific SERS detection of protein biomarkers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Antígeno Carcinoembrionário , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , DNA , Tecnologia
11.
Metabolites ; 12(10)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36295859

RESUMO

Proanthocyanidins (PACs) have been proven to exert antioxidant and anti-inflammatory effects. In this study, ultra-performance liquid chromatography (UPLC) coupled with linear ion trap-Orbitrap (LTQ-Orbitrap) high-resolution mass spectrometry was first employed to systematically screen PACs from the roots of Ephedra sinica Stapf, and its ethyl acetate extract (ERE) was found to contain PAC monomers and A-type dimeric proanthocyanidins, which were tentatively identified through characteristic fragmentation patterns. In vitro, the antioxidant activity of ERE was tested through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. In addition, ERE could inhibit the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In vivo, the preventative effects on dextran-sulfate-sodium-induced ulcerative colitis in mice was investigated. Mice were administered with ERE for 21 days, and during the last 7 days of the treatment period dextran sulfate sodium (DSS) was used to induce experimental colitis. The results showed that ERE treatment alleviated DSS-induced colitis, which was characterized by decreases in disease activity index (DAI) scores, spleen index and colon levels of TNF-α and IL-6, mitigation in pathological damage and oxidative stress and increases in colon length and IL-10 levels. In conclusion, supplementation of PACs derived from ERE may offer a new strategy for the treatment of ulcerative colitis. Moreover, our research will greatly facilitate better utilization of Ephedra plants.

12.
Front Chem ; 10: 1000709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105309

RESUMO

Nanozymes have attracted great interest owing to their marvelous advantages, such as high stability, facile preparation, and high tunability. In particular, iron sulfide-based nanozymes (termed as ISNs), as one of the most researched nanomaterials with versatile enzyme-mimicking properties, have proved their potential in biomedical applications. In this review, we briefly summarize the classification, catalytic mechanisms of ISNs and then principally introduce ISNs' biomedical applications in biosensors, tumor therapy, antibacterial therapy, and others, demonstrating that ISNs have promising potential for alleviating human health.

13.
J Nanobiotechnology ; 20(1): 271, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690820

RESUMO

Circulating tumour DNA (ctDNA) has emerged as an ideal biomarker for the early diagnosis and prognosis of gastric cancer (GC). In this work, a pump-free, high-throughput microfluidic chip coupled with catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) as the signal cascade amplification strategy (CHA-HCR) was developed for surface-enhanced Raman scattering (SERS) assays of PIK3CA E542K and TP53 (two GC-related ctDNAs). The chip consisted of six parallel functional units, enabling the simultaneous analysis of multiple samples. The pump-free design and hydrophilic treatment with polyethylene glycol (PEG) realized the automatic flow of reaction solutions in microchannels, eliminating the dependence on external heavy-duty pumps and significantly improving portability. In the reaction region of the chip, products generated by target-triggered CHA initiated the HCR, forming long nicked double-stranded DNA (dsDNA) on the Au nanobowl (AuNB) array surface, to which numerous SERS probes (Raman reporters and hairpin DNA-modified Cu2O octahedra) were attached. This CHA-HCR strategy generated numerous active "hot spots" around the Cu2O octahedra and AuNB surface, significantly enhancing the SERS signal intensity. Using this chip, an ultralow limit of detection (LOD) for PIK3CA E542K (1.26 aM) and TP53 (2.04 aM) was achieved, and the whole process was completed within 13 min. Finally, a tumour-bearing mouse model was established, and ctDNA levels in mouse serum at different stages were determined. To verify the experimental accuracy, the gold-standard qRT-PCR assay was utilized, and the results showed a high degree of consistency. Thus, this rapid, sensitive and cost-effective SERS microfluidic chip has potential as an ideal detection platform for ctDNA monitoring.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Neoplasias Gástricas , Animais , Técnicas Biossensoriais/métodos , Classe I de Fosfatidilinositol 3-Quinases , DNA/análise , Limite de Detecção , Camundongos , Microfluídica , Análise Espectral Raman/métodos , Neoplasias Gástricas/diagnóstico
14.
Int Immunopharmacol ; 109: 108907, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35691271

RESUMO

BACKGROUND: Sepsis is a life-threateningorgandysfunction caused by the cytokine storm induced by the severe bacterial infection. Excessive inflammatory responses are responsible for the lethal organ damage during the early stage of sepsis. Helminth infection and helminth-derived proteins have been identified to have the ability to immunomodulate the host immune system by reducing inflammation against inflammatory diseases. Trichinella spiralis cystatin (Ts-Cys) is a cysteine protease inhibitor with strong immunomodulatory functions on host immune system. Our previous studies have shown that excretory-secretory proteins of T. spiralis reduced sepsis-induced inflammation and Ts-Cys was able to inhibit macrophages to produce inflammatory cytokines. Whether Ts-Cys has a therapeutic effect on polymicrobial sepsis and related immunological mechanism are not yet known. METHODS: Sepsis was induced in BALB/c mice using cecal ligation and puncture (CLP), followed by intraperitoneal injection of 15 µg recombinant Ts-Cys (rTs-Cys). The therapeutic effect of rTs-Cys on sepsis was evaluated by observing the 72-hour survival rates of CLP-induced septic mice and the acute injury of lung and kidney through measuring the wet/dry weight ratio of lung, the levels of blood urea nitrogen (BUN) and creatinine (Cr) in sera and the tissue section pathology. The potential underlying mechanism was investigated using mouse bone marrow-derived macrophages (BMDMs) by observing the effect of rTs-Cys on LPS-stimulated macrophage polarization. The expression of genes associated with macrophage polarization in BMDMs and tissues of septic mice was measured by Western Blotting and qPCR. RESULTS: In this study, we demonstrated the treatment with rTs-Cys alleviated CLP-induced sepsis in mice with significantly reduced pathological injury in vital organs of lung and kidney and reduced mortality of septic mice. The further study identified that treatment with rTs-Cys promoted macrophage polarization from classically activated macrophage (M1) to alternatively activated macrophage (M2) phenotype via inhibiting TLR2/MyD88 signal pathway and increasing expression of mannose receptor (MR), inhibited pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) and increased regulatory anti-inflammatory cytokines (IL-10 and TGF-ß) in sera and tissues (lung and kidney) of mice with polymicrobial sepsis. CONCLUSIONS: Our results demonstrated that rTs-Cys had a therapeutic effect on sepsis through activating regulatory macrophages possibly via suppressing TLR2/MyD88 signal pathway. We also identified that rTs-Cys-induced M2 macrophage differentiation was associated with increased expression of MR on the surface of macrophages. Our results underscored the importance of MR in regulating macrophages during the treatment with rTs-Cys, providing another immunological mechanism in which helminths and their derived proteins modulate the host immune system. The findings in this study suggest that rTs-Cys is a potential therapeutic agent for the prevention and treatment of sepsis and other inflammatory diseases.


Assuntos
Cistatinas , Sepse , Trichinella spiralis , Animais , Cistatinas/genética , Cistatinas/metabolismo , Cistatinas/uso terapêutico , Citocinas/metabolismo , Proteínas de Helminto , Inflamação , Macrófagos , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , Sepse/tratamento farmacológico , Sepse/microbiologia , Receptor 2 Toll-Like/metabolismo
15.
J Ethnopharmacol ; 294: 115369, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35562091

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Celastrus orbiculatus Thunb., an important folk medicine, has long been used for the treatment of rheumatoid arthritis and its ethyl acetate extract (COE) has been reported to possess anticancer, antiinflammation and antiarthritic effects. However, the therapeutic effect and mechanism of COE treatment in rheumatoid arthritis has been rarely studied especially from the perspective of metabolomics. AIM OF STUDY: To reveal the therapeutic effects of COE on adjuvant-induced arthritis (AIA) rats through histopathological analysis, non-targeted metabolomics, and molecular docking study. MATERIALS AND METHODS: Forty-three Wistar rats were randomly divided into normal group, AIA model group, methotrexate group, and COE groups (80 mg/kg, 160 mg/kg and 320 mg/kg of ethyl acetate extract). Paw swelling and arthritis score were monitored through the experiment. Serum levels of tumor necrosis factor α (TNF-α) and nitric oxide were determined and histopathological evaluation was performed. Furthermore, Ultra-high performance liquid chromatography-linear trap quadrupole-Orbitrap-based metabolomics was employed to characterize metabolic changes of AIA rats after COE treatment and molecular docking was performed to predict the potential phytochemicals of COE against TNF-α. RESULTS: COE at three dosages could significantly relieve paw swelling and reduce arthritis scores of AIA rat. Histopathological analysis revealed remarkable decrease in synovial inflammation and bone erosion after COE treatment, especially at middle and high dosage. Additionally, COE down-regulated serum levels of TNF-α and nitric oxide. Serum metabolomics showed that 22 potential biomarkers for the COE treatment of AIA rats were identified, which were closely related to fatty acid metabolism, glycerophospholipid catabolism, and tryptophan metabolism. The molecular docking models predicted that olean-type triterpenes in COE may contribute most to therapeutic effects of rheumatoid arthritis through targeting TNF-α. CONCLUSIONS: COE could significantly relieve the arthritic symptoms in AIA rats and the ultra-high performance liquid chromatography-mass spectrometry based metabolomics proved to be an efficient method to characterize subtle metabolic changes of AIA rats after COE treatment.


Assuntos
Artrite Experimental , Artrite Reumatoide , Celastrus , Acetatos , Animais , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Celastrus/química , Metabolômica , Simulação de Acoplamento Molecular , Óxido Nítrico , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
16.
Int J Oncol ; 60(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35147201

RESUMO

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that a pair of data panels featured between Figs. 4 and 7 contained overlapping data such that the data were derived from the same original source where they were intending to depict the results from experiments performed under different experimental conditions, and a pair of the data panels featured in Fig. 8 for the ß­catenin data also appeared to show overlapping data. The authors were able to re­examine their original data, and have identified the data that were intended to have been shown for these figure parts. The corrected versions of Fig. 4 (showing the correct data for the LV­DJ­1/migration experiment in Fig. 4A), Fig. 7 (showing the correct data for the LV­DJ­1 + XAV939/migration experiment) and Fig. 8 (showing the correct data for the LV­siRNA­DJ­1 experiment) are shown on the subsequent pages. The authors confirm that these inadvertent errors did not have any major impact on the conclusions reported in their paper, are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 56: 1115­1128, 2020; DOI: 10.3892/ijo.2020.5005].

17.
Front Pharmacol ; 12: 619732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867982

RESUMO

New strategies and drugs are urgently needed to improve the treatment of hepatocellular carcinoma (HCC). Vasculogenic mimicry (VM) has been elucidated being associated with the progression of HCC and anti-VM could be a promising strategy. Celastrus orbiculatu s extract (COE), a mixture of 26 compounds isolated from the Chinese Herb Celastrus Orbiculatus Vine, has been elucidated to be able to disrupt VM formation in HCC. This study aims to dissect and identify the potential targets of COE on anti-VM formation both in vitro and in vivo that are distinct from our previous study. Proteomics analysis was used to identify differential proteins in HCC cells treated with or without COE (Data are available via ProteomeXchange with identifier PXD022203). Cells invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation in vitro. RT-PCR and Western Blot were used to examine changes of mRNA and protein respectively. Clinical resected samples were applied to confirm association between VM formation and identified targets. Subcutaneous xenograft tumor model was established to observe tumor growth and VM formation in vivo. PAS-CD34 dual staining was used to detect VM in vivo. A total of 194 proteins were identified to be differentially expressed in HCC cells treated with or without COE. In the 93 down-regulated proteins EphA2 stood out to be regulated on both RNA and protein level. Disruption EphA2 using COE or NVP inhibited VM formation and decreased VM associated biomarkers. In xenograft mouse model, COE inhibited tumor growth and VM formation via down-regulating EphA2. Taken together, our results indicate that COE could be used in HCC treatment because of its promising anti-VM effect.

18.
Anticancer Agents Med Chem ; 21(8): 1037-1046, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32951585

RESUMO

BACKGROUND: This study aimed to determine the effect and mechanism of Xiaoaiping (XAP) injection combined with S-1 in inhibiting the invasion and metastasis of human GC cells. METHODS: BGC-823 and MGC-803 cells were incubated in vitro, and the effects of treatment on the cytotoxicity and proliferation of BGC-823 and MGC-803 cells were evaluated by MTT assay. Cell adhesion tests and Transwell assays were used to detect the effects of Xiaoaiping injection combined with S-1 on the metastatic ability of BGC-823 and MGC-803 cells. The expression of VEGF, Metalloproteinases (MMPs) and proteins related to the Epithelial-Mesenchymal Transition (EMT) were detected by Western blotting. Meanwhile, a tumour model was established in nude mice, and the effect of XAP combined with S-1 on BGC-823 cells in vivo was studied. RESULTS: Compared with the single drug group, the combination of XAP with S-1 increased the inhibition rate (P<0.05). The adhesion test showed that the combination group significantly inhibited the adhesion of BGC-823 and MGC-803 cells (P<0.05). The combination of XAP with S-1 reduced the migration and invasion potential of human GC BGC-823 and MGC-803 cells. Western blotting showed that the expression of VEGF, MMP-9, Ncadherin and vimentin was decreased and E-cadherin expression was increased in the combination group compared with these expression values in either the XAP or S-1 alone group (P<0.05). In vivo, we found that XAP combined with S-1 had a significant inhibitory effect on the growth of tumours compared with XAP or S-1 alone. Immunohistochemistry showed that XAP combined with S-1 was able to enhance the levels of E-cadherin and downregulate N-cadherin and vimentin. CONCLUSION: The combination of XAP with S-1 can enhance the inhibitory effect of a single drug on proliferation, invasion and metastasis. The mechanism may be related to the decrease in the expression of VEGF and MMP-9 proteins and the effect on EMT.


Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ácido Oxônico/farmacologia , Tegafur/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caderinas/genética , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Desenvolvimento de Medicamentos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional Chinesa , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vimentina/genética , Vimentina/metabolismo
20.
Int J Oncol ; 56(5): 1115-1128, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32319588

RESUMO

DJ­1, an oncogene, has been reported to be an independent prognostic indicator of poor survival in patients with esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the role of DJ­1 in tumor cell proliferation and invasion in ESCC and its underlying mechanisms. It was observed that the expression level of DJ­1 was upregulated and positively associated with EMT biomarkers in 84 human ESCC tissue specimens. Overexpression and knockdown experiments demonstrated that DJ­1 was involved in proliferation, migration, invasion and EMT in ECA­109 cells in vitro and extensive peritoneal seeding in a peritoneal dissemination mice model. Furthermore, the present data revealed that DJ­1 could activate the Wnt/ß­catenin signaling pathway, which mediates the EMT and metastasis in ESCC. In conclusions, DJ­1 promoted proliferation, invasion, metastasis and the EMT in ESCC via activation of the Wnt/ß­catenin signal pathway. The present results suggested DJ­1 could represent a promising therapeutic target for the prevention and treatment of ESCC­related metastasis.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Proteína Desglicase DJ-1/genética , Proteína Desglicase DJ-1/metabolismo , Regulação para Cima , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Transplante de Neoplasias , Prognóstico , Via de Sinalização Wnt
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