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1.
J Cell Mol Med ; 28(10): e18395, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38774995

RESUMEN

Tumour-associated macrophages (TAMs), encompassing M1 and M2 subtypes, exert significant effects on osteosarcoma (OS) progression and immunosuppression. However, the impacts of TAM-derived biomarkers on the progression of OS remains limited. The GSE162454 profile was subjected to single-cell RNA (scRNA) sequencing analysis to identify crucial mediators between TAMs and OS cells. The clinical features, effects and mechanisms of these mediators on OS cells and tumour microenvironment were evaluated via biological function experiments and molecular biology experiments. Phosphodiesterase 4C (PDE4C) was identified as a pivotal mediator in the communication between M2 macrophages and OS cells. Elevated levels of PDE4C were detected in OS tissues, concomitant with M2 macrophage level, unfavourable prognosis and metastasis. The expression of PDE4C was observed to increase during the conversion process of THP-1 cells to M2 macrophages, which transferred the PDE4C mRNA to OS cells through exosome approach. PDE4C increased OS cell proliferation and mobility via upregulating the expression of collagens. Furthermore, a positive correlation was observed between elevated levels of PDE4C and increased TIDE score, decreased response rate following immune checkpoint therapy, reduced TMB and diminished PDL1 expression. Collectively, PDE4C derived from M2 macrophages has the potential to enhance the proliferation and mobility of OS cells by augmenting collagen expression. PDE4C may serve as a valuable biomarker for prognosticating patient outcomes and response rates following immunotherapy.


Asunto(s)
Neoplasias Óseas , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4 , Inmunoterapia , Macrófagos , Osteosarcoma , Microambiente Tumoral , Humanos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Neoplasias Óseas/inmunología , Neoplasias Óseas/patología , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/genética , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Macrófagos/metabolismo , Macrófagos/inmunología , Metástasis de la Neoplasia , Osteosarcoma/patología , Osteosarcoma/inmunología , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/terapia , Pronóstico , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo
2.
Molecules ; 29(7)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38611789

RESUMEN

Natural chemicals derived from herbal plants have recently been recognized as potentially useful treatment alternatives owing to their ability to target a wide range of important biological molecules. Cynaroside is one of these natural compounds with promising anticancer activity for numerous tumor types. Nevertheless, the anticancer effects and molecular mechanisms of action of cynaroside on colorectal cancer (CRC) remain unclear. In this study, cynaroside was found to markedly inhibit CRC cell proliferation and colony formation in vitro. Cynaroside also inhibited cell proliferation in vivo and decreased the expression of KI67, a cell nuclear antigen. RNA sequencing revealed 144 differentially expressed genes (DEGs) in HCT116 cells and 493 DEGs in RKO cells that were enriched in the cell cycle signaling pathway. Cell division cycle 25A (CDC25A), a DEG widely enriched in the cell cycle signaling pathway, is considered a key target of cynaroside in CRC cells. Cynaroside also inhibited DNA replication and arrested cells in the G1/S phase in vitro. The expression levels of CDC25A and related G1-phase proteins were significantly elevated after CDC25A overexpression in CRC cells, which partially reversed the inhibitory effect of cynaroside on CRC cell proliferation and G1/S-phase arrest. In summary, cynaroside may be used to treat CRC as it inhibits CDC25A expression.


Asunto(s)
Neoplasias Colorrectales , Glucósidos , Humanos , Puntos de Control de la Fase G1 del Ciclo Celular , Luteolina , Neoplasias Colorrectales/tratamiento farmacológico
3.
Angew Chem Int Ed Engl ; : e202408064, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853147

RESUMEN

Tumor-specific activatable long-wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (F1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH-activatable cyanine-based LW PSs (LET-R, R = H, Cl, Br, I), among which the activated LET-I exhibits strong light absorption at 808 nm and a remarkable 3.2-fold enhancement in F1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual-modal imaging-escorted complete photodynamic eradication of tumors by the folic acid (FA)-modified LET-I probe (LET-I-FA), under the ultralow 808 nm laser power density (0.2 W cm-2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.

4.
J Cell Mol Med ; 27(17): 2533-2546, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37488774

RESUMEN

The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from PSCs act as mediators for communication in PC. This study aimed to explore the role of PSC-derived exosomal small RNAs derived from tRNAs (tDRs) in PC cells. Exosomes from PSCs were extracted and used to detect their effects on PC cell proliferation, migration and invasion. Exosomal tDRs profiling was performed to identify PSC-derived exosomal tDRs. ISH and qRT-PCR were used to examine the tRF-19-PNR8YPJZ levels and clinical value in clinical samples. The biological function of exosomal tRF-19-PNR8YPJZ was determined using the CCK-8, clone formation, wound healing and transwell assays, subcutaneous tumour formation and lung metastatic models. The relationship between the selected exosomal tRF-19-PNR8YPJZ and AXIN2 was determined by RNA sequencing, luciferase reporter assay. PSC-derived exosomes promoted the proliferation, migration, and invasion of PC cells. Novel and abundant tDRs are found to be differentially expressed in PANC-1 cells after treatment with PSC-derived exosomes, such as tRF-19-PNR8YPJZ. PC tissue samples showed markedly higher levels of tRF-19-PNR8YPJZ than normal controls. Patients with PC exhibiting high tRF-19-PNR8YPJZ expression had a highly lymph node invasion, metastasis, perineural invasion, advanced clinical stage and poor overall survival. Exosomal tRF-19-PNR8YPJZ from PSCs targeted AXIN2 in PC cells and decreased its expression, thus activating the Wnt pathway and promoting proliferation and metastasis. Exosomal tRF-19-PNR8YPJZ from PSCs promoted proliferation and metastasis in PC cells via AXIN2.


Asunto(s)
Exosomas , MicroARNs , Neoplasias Pancreáticas , Humanos , Células Estrelladas Pancreáticas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias Pancreáticas/patología , Exosomas/metabolismo , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Proteína Axina/genética , Proteína Axina/metabolismo , Neoplasias Pancreáticas
5.
J Cell Mol Med ; 27(13): 1820-1835, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37248957

RESUMEN

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation-associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation- and ferroptosis-subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high-risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high-risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Ferroptosis/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Inmunoterapia , Inflamación/genética , Microambiente Tumoral/genética , Arildialquilfosfatasa
6.
Cell Commun Signal ; 21(1): 46, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36864422

RESUMEN

BACKGROUND: Early metastasis is a hallmark of osteosarcoma (OS), a highly common type of malignant tumor. Members of the potassium inwardly rectifying channel family exert oncogenic effects in various cancers. However, the role of the potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) in OS is unclear. METHODS: The expression of KCNJ2 in OS tissues and cell lines was measured using bioinformatic analysis, immunohistochemistry, and western blotting. Wound-healing assays, Transwell assays, and lung metastasis models were used to analyze the effects of KCNJ2 on mobility of OS cells. The molecular mechanisms linking KCNJ2 and HIF1α in OS were explored by mass spectrometry analysis, immunoprecipitation, ubiquitination detection, and chromatin-immunoprecipitation quantitative real-time polymerase chain reaction. RESULTS: KCNJ2 was found to be overexpressed in advanced-stage OS tissues, as well as in cells with high metastatic potential. High expression of KCNJ2 was associated with a shorter survival rate of OS patients. KCNJ2-inhibition repressed the metastasis of OS cells, whereas KCNJ2-elevation induced the opposite effects. Mechanistically, KCNJ2 binds to HIF1α and inhibits its ubiquitination, thus increasing the expression of HIF1α. Interestingly, HIF1α binds directly to the KCNJ2 promoter and increases its transcription under hypoxic conditions. CONCLUSION: Taken together, our results indicated that a KCNJ2/HIF1α positive feedback loop exists in OS tissues, which significantly promotes OS cell metastasis. This evidence may contribute to the diagnosis and treatment of OS. Video Abstract.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Canales de Potasio de Rectificación Interna , Humanos , Retroalimentación , Bioensayo , Línea Celular , Neoplasias Óseas/genética , Canales de Potasio de Rectificación Interna/genética
7.
Molecules ; 28(12)2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37375197

RESUMEN

According to previous research, turmeric seeds exhibit anti-inflammatory, anti-malignancy, and anti-aging properties due to an abundance of terpinen-4-ol (T4O). Although it is still unclear how T4O works on glioma cells, limited data exist regarding its specific effects. In order to determine whether or not glioma cell lines U251, U87, and LN229 are viable, CCK8 was used as an assay and a colony formation assay was performed using different concentrations of T4O (0, 1, 2, and 4 µM). The effect of T4O on the proliferation of glioma cell line U251 was detected through the subcutaneous implantation of the tumor model. Through high-throughput sequencing, a bioinformatic analysis, and real-time quantitative polymerase chain reactions, we identified the key signaling pathways and targets of T4O. Finally, for the measurement of the cellular ferroptosis levels, we examined the relationship between T4O, ferroptosis, and JUN and the malignant biological properties of glioma cells. T4O significantly inhibited glioma cell growth and colony formation and induced ferroptosis in the glioma cells. T4O inhibited the subcutaneous tumor proliferation of the glioma cells in vivo. T4O suppressed JUN transcription and significantly reduced its expression in the glioma cells. The T4O treatment inhibited GPX4 transcription through JUN. The overexpression of JUN suppressed ferroptosis in the cells rescued through T4O treatment. Taken together, our data suggest that the natural product T4O exerts its anti-cancer effects by inducing JUN/GPX4-dependent ferroptosis and inhibiting cell proliferation, and T4O will hope-fully serve as a prospective compound for glioma treatment.


Asunto(s)
Ferroptosis , Glioma , Humanos , Genes jun , Estudios Prospectivos , Línea Celular Tumoral , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , Proliferación Celular
8.
Molecules ; 28(24)2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38138552

RESUMEN

Gastrodin, the primary bioactive compound found in Gastrodia elata, has been shown to exhibit neuroprotective properties in a range of neurological disorders. However, the precise mechanisms through which gastrodin influences glioma cells remain unclear, and there is a scarcity of data regarding its specific effects. To ascertain the viability of glioma cell lines LN229, U251, and T98, the CCK-8 assay, a colony formation assay, and a 3D culture model were employed, utilizing varying concentrations of gastrodin (0, 5, 10, and 20 µM). Gastrodin exhibited a notable inhibitory effect on the growth of glioma cells, as evidenced by its ability to suppress colony formation and spheroid formation. Additionally, gastrodin induced ferroptosis in glioma cells, as it can increase the levels of reactive oxygen species (ROS) and peroxidized lipids, and reduced the levels of glutathione. Using a subcutaneous tumor model, gastrodin was found to significantly inhibit the growth of the T98 glioma cell line in vivo. Using high-throughput sequencing, PPI analysis, and RT-qPCR, we successfully identified Homeobox D10 (HOXD10) as the principal target of gastrodin. Gastrodin administration significantly enhanced the expression of HOXD10 in glioma cells. Furthermore, treatment with gastrodin facilitated the transcription of ACSL4 via HOXD10. Notably, the inhibition of HOXD10 expression impeded ferroptosis in the cells, which was subsequently restored upon rescue with gastrodin treatment. Overall, our findings suggest that gastrodin acts as an anti-cancer agent by inducing ferroptosis and inhibiting cell proliferation in HOXD10/ACSL4-dependent pathways. As a prospective treatment for gliomas, gastrodin will hopefully be effective.


Asunto(s)
Ferroptosis , Glioma , Humanos , Ferroptosis/genética , Regulación hacia Arriba , Genes Homeobox , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , Línea Celular Tumoral
9.
Molecules ; 28(4)2023 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-36838737

RESUMEN

Luteoloside has shown anti-inflammatory, antiviral, and antitumor properties. However, the effect and mechanism of luteoloside on neuroblastoma cells remain unknown. The proliferation of human neuroblastoma cells (SH-SY5Y and SK-N-AS) treated with different concentrations of luteoloside (0, 12.5, 25, and 50 µM) was detected by the MTT assay and colony formation assay. Cell apoptosis and cell cycle were examined by Hoechst staining and flow cytometry. A subcutaneous tumorigenesis model was established in nude mice to evaluate the effect of luteoloside on tumor growth in vivo. Bioinformatics, molecular docking techniques, and cellular thermal shift assays were utilized to predict the potential targets of luteoloside in neuroblastoma. The p38 MAPK inhibitor SB203580 was used to confirm the role of p38 MAPK. Luteoloside inhibited the proliferation of neuroblastoma cells in vitro and in vivo. Luteoloside slightly induced cellular G0/G1 phase arrest and reduced the expression levels of G0/G1 phase-related genes and the proteins cyclin D1, CDK4, and C-myc, which are downregulated by p38 MAPK pathways. Meanwhile, p38 was identified as the target of luteoloside, and inhibition of p38 MAPK reversed the inhibitory effect of luteoloside on neuroblastoma cells. Luteoloside is a potential anticancer drug for treating neuroblastoma by activating p38 MAPK.


Asunto(s)
Neuroblastoma , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Ratones , Humanos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proliferación Celular , Ratones Desnudos , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Neuroblastoma/tratamiento farmacológico , Apoptosis , Fase G1
10.
Zhongguo Zhong Yao Za Zhi ; 48(14): 3904-3912, 2023 Jul.
Artículo en Zh | MEDLINE | ID: mdl-37475082

RESUMEN

The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Proliferación Celular , Neoplasias de la Mama/tratamiento farmacológico , Proteína p53 Supresora de Tumor/genética , Simulación del Acoplamiento Molecular
11.
Anal Chem ; 94(23): 8399-8408, 2022 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-35634985

RESUMEN

Retaining intrinsic photophysical performance and efficient therapeutic efficacy of cyanine dyes in the second near-infrared (NIR-II) biowindow are challenges in the biomedical field. Herein, we develop a metal ion-assisted NIR-II fluorophore assembly strategy to modulate molecular arrangement behavior, thus overcoming the drawbacks and retaining the photophysical performance of cyanine dyes in aqueous media for cancer phototheranostics. By screening a series of metal ion-assisted fluorophore assemblies, we remarkably found gadolinium-based metallo-dye-supramolecular nanoassembly (denoted as Gd@IR1064) with the intrinsic optical properties of NIR-II cyanine dye (IR1064). Most intriguingly, the as-prepared Gd@IR1064 not only exhibits deep-tissue-penetrating NIR-II photoacoustic, fluorescence, and magnetic resonance imaging ability but also possesses enhanced photothermal conversion performance-induced hyperthermia, achieving a significant tumor elimination effect. Our study provides a promising guide for modulating dye arrangement with unique photophysical performance for biomedical applications.


Asunto(s)
Hipertermia Inducida , Neoplasias , Línea Celular Tumoral , Colorantes Fluorescentes/farmacología , Gadolinio , Humanos , Hipertermia Inducida/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fototerapia , Medicina de Precisión , Nanomedicina Teranóstica/métodos
12.
J Nanobiotechnology ; 20(1): 53, 2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35090484

RESUMEN

BACKGROUND: Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic modality that involves sonosensitizers and low-intensity ultrasound. However, owing to the rapid recombination of charge carriers, most of the sonosensitizers triggered poor reactive oxygen species (ROS) generation, resulting in unsatisfactory sonodynamic therapeutic effects. RESULTS: Herein, a photo/sono-responsive nanoplatform was developed through the in-situ systhesis of TiO2-x on the surface of two-dimensional MXene (titanium carbide, Ti3C2) for photoacoustic/photothermal bimodal imaging-guided near-infrared II (NIR-II) photothermal enhanced SDT of tumor. Because of several oxygen vacancies and smaller size (~ 10 nm), the in-situ formed TiO2-x nanoparticles possessed narrow band gap (2.65 eV) and high surface area, and thus served as a charge trap to restrict charge recombination under ultrasound (US) activation, resulting in enhanced sonodynamic ROS generation. Moreover, Ti3C2 nanosheets induced extensive localized hyperthermia relieves tumor hypoxia by accelerating intratumoral blood flow and tumor oxygenation, and thus further strengthened the efficacy of SDT. Upon US/NIR-II laser dual-stimuli, Ti3C2@TiO2-x nanoplatform triggered substantial cellular killing in vitro and complete tumor eradication in vivo, without any tumor recurrence and systemic toxicity. CONCLUSION: Our work presents the promising design of photo/sono-responsive nanoplatform for cancer nanotheranostics.


Asunto(s)
Nanopartículas , Neoplasias , Terapia por Ultrasonido , Línea Celular Tumoral , Humanos , Nanopartículas/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Medicina de Precisión , Titanio , Terapia por Ultrasonido/métodos
13.
Angew Chem Int Ed Engl ; 61(42): e202204584, 2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-35853827

RESUMEN

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2 O2 ) generation. Meanwhile, CAT catalyzes H2 O2 into O2 , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.


Asunto(s)
Nanopartículas , Neoplasias , Catalasa , Línea Celular Tumoral , Polímeros de Fluorocarbono , Glucosa , Glucosa Oxidasa , Humanos , Peróxido de Hidrógeno , Lactatos , Neoplasias/patología
14.
J Cell Physiol ; 236(3): 2087-2098, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32749678

RESUMEN

Hypoxia is involved in the development of pancreatic cancer (PC). The responses of hypoxia-associated genes and their regulated mechanisms are largely unknown. In this study, through bioinformatic analysis and quantitative real-time polymerase chain reaction, the YEATS domain containing 2 (YEATS2) was determined to be a key hypoxia-associated gene. It was increased in PC cells under hypoxia, upregulated in PC tissues, and predicted poor outcome. YEATS2 inhibition decreased the proliferation and migration of PC cells under both normoxia and hypoxia in vitro as well as proliferation and metastasis in vivo. We found that hypoxia-inducible factor 1α (HIF1α) regulated the expression of YEATS2 via binding to the hypoxia response element (HRE) of YEATS2 and coexpressed with YEATS2 in PC tissues. Overexpression of YEATS2 blocked the inhibitory effects of HIF1α silence on PC cell proliferation and migration under hypoxia. Collectively, our study revealed that YEATS2 is a target gene of HIF1α and promotes PC development under hypoxia.


Asunto(s)
Movimiento Celular , Proteínas Cromosómicas no Histona/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Hipoxia de la Célula/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas Cromosómicas no Histona/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Biológicos , Metástasis de la Neoplasia , Neoplasias Pancreáticas/genética , Proteínas Represoras/metabolismo , Resultado del Tratamiento , Regulación hacia Arriba/genética
15.
Gastroenterology ; 159(4): 1252-1261.e5, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32562721

RESUMEN

BACKGROUND AND AIMS: Up to 30% of adenomas might be missed during screening colonoscopy-these could be polyps that appear on-screen but are not recognized by endoscopists or polyps that are in locations that do not appear on the screen at all. Computer-aided detection (CADe) systems, based on deep learning, might reduce rates of missed adenomas by displaying visual alerts that identify precancerous polyps on the endoscopy monitor in real time. We compared adenoma miss rates of CADe colonoscopy vs routine white-light colonoscopy. METHODS: We performed a prospective study of patients, 18-75 years old, referred for diagnostic, screening, or surveillance colonoscopies at a single endoscopy center of Sichuan Provincial People's Hospital from June 3, 2019 through September 24, 2019. Same day, tandem colonoscopies were performed for each participant by the same endoscopist. Patients were randomly assigned to groups that received either CADe colonoscopy (n=184) or routine colonoscopy (n=185) first, followed immediately by the other procedure. Endoscopists were blinded to the group each patient was assigned to until immediately before the start of each colonoscopy. Polyps that were missed by the CADe system but detected by endoscopists were classified as missed polyps. False polyps were those continuously traced by the CADe system but then determined not to be polyps by the endoscopists. The primary endpoint was adenoma miss rate, which was defined as the number of adenomas detected in the second-pass colonoscopy divided by the total number of adenomas detected in both passes. RESULTS: The adenoma miss rate was significantly lower with CADe colonoscopy (13.89%; 95% CI, 8.24%-19.54%) than with routine colonoscopy (40.00%; 95% CI, 31.23%-48.77%, P<.0001). The polyp miss rate was significantly lower with CADe colonoscopy (12.98%; 95% CI, 9.08%-16.88%) than with routine colonoscopy (45.90%; 95% CI, 39.65%-52.15%) (P<.0001). Adenoma miss rates in ascending, transverse, and descending colon were significantly lower with CADe colonoscopy than with routine colonoscopy (ascending colon 6.67% vs 39.13%; P=.0095; transverse colon 16.33% vs 45.16%; P=.0065; and descending colon 12.50% vs 40.91%, P=.0364). CONCLUSIONS: CADe colonoscopy reduced the overall miss rate of adenomas by endoscopists using white-light endoscopy. Routine use of CADe might reduce the incidence of interval colon cancers. chictr.org.cn study no: ChiCTR1900023086.


Asunto(s)
Pólipos Adenomatosos/patología , Neoplasias del Colon/patología , Pólipos del Colon/patología , Colonoscopía , Aprendizaje Profundo , Diagnóstico por Computador , Interpretación de Imagen Asistida por Computador , Adolescente , Adulto , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diagnóstico Erróneo , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Adulto Joven
16.
Anal Chem ; 93(51): 17103-17109, 2021 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-34905355

RESUMEN

Visualization of glutathione (GSH) enables us to understand GSH-related pathophysiological processes in living subjects. Currently, in vivo visualization methods of GSH are based on visible or first near-infrared (NIR-I) window fluorescence (FL) probes, which possess limitations due to their low tissue penetration depth and strong tissue autofluorescence. Herein, we developed a GSH-activatable second near-infrared (NIR-II) window FL probe (denoted as LET-7) for highly sensitive and selective visualization of GSH in vivo. LET-7, composed of an anionic polymethylcyanide skeleton linked with a FL quenching group of 3,5-bis(trifluoromethyl)benzenethiol, can be specifically activated by GSH, thus triggering a significant NIR-II FL emission enhancement with excellent photostability, which enables us to efficiently distinguish GSH from closely related low-molecular-weight biothiols. The limit of detection of LET-7 for GSH was determined to be as low as 85 nM. Most intriguingly, the in vivo studies demonstrated that LET-7 showed high sensitivity and good selectivity toward GSH. Therefore, our study provides a solution to design activatable NIR-II FL probes for in vivo imaging of GSH and other disease-related biomarkers.


Asunto(s)
Colorantes Fluorescentes , Glutatión , Diagnóstico por Imagen , Fluorescencia , Humanos
17.
J Nanobiotechnology ; 19(1): 266, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488789

RESUMEN

BACKGROUND: Acute kidney injury (AKI) with high mortality rates is associated with an excess of reactive oxygen/nitrogen species (RONS) within kidney tissues. Recently, nanomedicine antioxidant therapy has been used to alleviate AKI. Herein, we synthesized ultrasmall Prussian blue nanozymes (PB NZs, 4.5 nm) as theranostic agents for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided AKI treatment. RESULTS: PB NZs exhibited multi-enzyme mimetic abilities, promoting the effective elimination of RONS both in vitro and in vivo. Moreover, benefiting from their imaging contrast properties, the rapid renal accumulation of PB NZs was verified by in vivo PA/MR dual-modal imaging. Due to their excellent enrichment in the kidney and unique multi-enzyme mimetic abilities, ultrasmall PB NZs displayed superior AKI treatment efficacy compared with that of amifostine in two clinically relevant types of AKI induced murine models (either by rhabdomyolysis or cisplatin). CONCLUSION: Our findings suggested ultrasmall PB NZs, as nanozyme theranostics, have great potential for AKI management.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Ferrocianuros/farmacología , Medicina de Precisión/métodos , Lesión Renal Aguda/patología , Animales , Antioxidantes/farmacología , Cisplatino/farmacología , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Ratones , Ratones Endogámicos BALB C , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno
19.
Nano Lett ; 20(8): 6051-6058, 2020 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-32687372

RESUMEN

Solar-driven interfacial steam generation is a promising technique for clean water production because it can minimize thermal loss by localizing solar-to-heat conversion at the air/liquid interface. Here we report an integrated solar evaporator by partially growing 2D polypyrrole microsheets within a melamine foam through chemical vapor polymerization. These microsheets can induce multiple light reflections within the foam, enable omnidirectional light absorption, provide abundant surfaces to promote heat transfer, and achieve spatially defined hydrophobicity to facilitate vapor escape. Meanwhile, the inherent hydrophilicity of the bottom part of the foam promotes spontaneous upward water transport and suppresses heat loss. The composite foam exhibits an excellent apparent evaporation rate of ∼2 kg/(m2·h) and solar-to-vapor efficiency of ∼91%. The combined advantages of large surface area, high efficiency, low cost, all-weather application, excellent durability, and scalable manufacturing make our integrated design promising for fabricating large-scale solar steam generation systems that are suitable for practical clean water production.

20.
Bioconjug Chem ; 31(9): 2072-2084, 2020 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-32786372

RESUMEN

Croconaine (CR) dyes, the donor-acceptor-donor (D-A-D) type zwitterionic compounds with extended π-conjugation, can be readily synthesized via a straightforward condensation reaction. They have received much attention in bioimaging and theranostics, owing to their tailored structures and fascinating near-infrared (NIR) photophysical properties. In this topical review, we summarize the recent advances in biomedical applications for CR dyes. First, we introduce the classification and optical performance of CR dyes. Next, we highlight the chemistry and applications of CR dyes in bioimaging and theranostics. Finally, the summary and prospects of CR dyes for bioimaging and theranostics are discussed.


Asunto(s)
Colorantes/análisis , Imagen Óptica/métodos , Nanomedicina Teranóstica/métodos , Animales , Humanos , Modelos Moleculares
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