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1.
ACS Nano ; 18(11): 8325-8336, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38447099

RESUMO

Radiotherapy is a mainstay treatment used in clinics for locoregional therapy, although it still represents a great challenge to improve the sensitivity and accuracy of radiotherapy for tumors. Here, we report the conjugated polymer, polydiiododiacetylene (PIDA), with an iodine content of 84 wt %, as a highly effective computed tomography (CT) contrast agent and tumor microenvironment-responsive radiosensitizer. PIDA exhibited several key properties that contribute to the improvement of precision radiotherapy. The integrated PIDA nanofibers confined within the tumor envelope demonstrated amplified CT intensity and prolonged retention, providing an accurate calculation of dose distribution and precise radiation delivery for CT image-guided radiotherapy. Therefore, our strategy pioneers PIDA nanofibers as a bridge to cleverly connect a fiducial marker to guide accurate radiotherapy and a radiosensitizer to improve tumor sensitivity, thereby minimizing potential damage to surrounding tissues and facilitating on-demand therapeutic intervention in tumors.


Assuntos
Nanofibras , Neoplasias , Polímero Poliacetilênico , Radiossensibilizantes , Radioterapia Guiada por Imagem , Humanos , Carbono , Microambiente Tumoral , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico
2.
Sci Bull (Beijing) ; 69(8): 1091-1099, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38395650

RESUMO

Controlling the atomic arrangement of elemental atoms in intermetallic catalysts to govern their surface and subsurface properties is a crucial but challenging endeavor in electrocatalytic reactions. In hydrogen evolution reaction (HER), adjusting the d-band center of the conventional noble-metallic Pt by introducing Fe enables the optimization of catalytic performance. However, a notable gap exists in research on the effective transition from disordered Fe/Pt alloys to highly ordered intermetallic compounds (IMCs) such as FePt3 in the alkaline HER, hampering their broader application. In this study, a series of catalysts FePt3-xH (x = 5, 6, 7, 8 and 9) supported on carbon nanotubes (CNTs) were synthesized via a simple impregnation method, along with a range of heat treatment processes, including annealing in a reductive atmosphere, to regulate the order degree of the arrangement of Fe/Pt atoms within the FePt3 catalyst. By using advanced microscopy and spectroscopy techniques, we systematically explored the impact of the order degree of FePt3 in the HER. The as-prepared FePt3-8H exhibited notable HER catalytic activity with low overpotentials (η = 37 mV in 1.0 mol L-1 KOH) at j = 10 mA cm-2. The surface of the L12 FePt3-8H catalyst was demonstrated to be Pt-rich. The Pt on the surface was not easily oxidized due to the unique Fe/Pt coordination, resulting in significant enhancement of HER performance.

3.
Eur J Cancer ; 199: 113532, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38241820

RESUMO

BACKGROUND: Ovarian cancer (OV) is a prevalent and deadly disease with high mortality rates. The development of accurate prognostic tools and personalized therapeutic strategies is crucial for improving patient outcomes. METHODS: A graph-based deep learning model, the Ovarian Cancer Digital Pathology Index (OCDPI), was introduced to predict prognosis and response to adjuvant therapy using hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). The OCDPI was developed using formalin-fixed, paraffin-embedded (FFPE) WSIs from the TCGA-OV cohort, and was externally validated in two independent cohorts from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and Harbin Medical University Cancer Hospital (HMUCH). RESULTS: The OCDPI showed prognostic ability for overall survival prediction in the PLCO (HR, 1.916; 95% CI, 1.380-2.660; log-rank test, P < 0.001) and HMUCH (HR, 2.796; 95% CI, 1.404-5.568; log-rank test, P = 0.0022) cohorts. Patients with low OCDPI experienced better survival benefits and lower recurrence rates following adjuvant therapy compared to those with high OCDPI. Multivariable analyses, adjusting for clinicopathological factors, consistently identified OCDPI as an independent prognostic factor across all cohorts (all P < 0.05). Furthermore, OCDPI performed well in patients with low-grade tumors or fresh-frozen slides, and could differentiate between HRD-deficient or HRD-intact patients with and without sensitivity to adjuvant therapy. CONCLUSION: The results from this multicenter cohort study indicate that the OCDPI may serve as a valuable and labor-saving tool to improve prognostic and predictive clinical decision-making in patients with OV.


Assuntos
Aprendizado Profundo , Neoplasias Ovarianas , Feminino , Humanos , Estudos de Coortes , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Prognóstico , Estudos Retrospectivos
4.
Macromol Rapid Commun ; 44(23): e2300412, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37713720

RESUMO

Polydiacetylenes, as a class of conjugated polymers with alternating conjugated C═C and C≡C bonds, have emerged as a promising probe material for biomedical Raman imaging, given their ultrastrong Raman scattering intensity. However, the relationship between the structure, especially the molecular length of polydiacetylenes, and their Raman scattering intensity remains unclear. In this work, a series of water-soluble polydiacetylenes, namely poly(deca-4,6-diynedioic acid) (PDDA) with different molecular weights (MWs), is prepared through controlled polymerization and degradation. The ultraviolet-visible (UV-vis) absorption spectroscopic and Raman spectroscopic studies on these polymers reveal that the Raman scattering intensity of PDDA increases nonlinearly with the MW. The MW-Raman scattering intensity relationship in the polymerization process is completely different from that in the degradation process. In contrast, the Raman scattering intensity increases more linearly with the maximal absorbance of the polymer, and the relationship between the Raman scattering intensity and the maximal absorbance of PDDA in the polymerization process is consistent with that in the degradation process. The Raman scattering intensity of PDDA hence exhibits a better dependence on the effective conjugation length of the polymer, which should guide the future design of conjugated polymers for Raman imaging applications.


Assuntos
Polímeros , Análise Espectral Raman , Polímeros/química , Análise Espectral Raman/métodos , Polímero Poliacetilênico/química , Peso Molecular
5.
Transl Res ; 262: 12-24, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37499745

RESUMO

Ovarian cancer (OV) is the most lethal gynecological malignancy and requires improved early detection methods and more effective intervention to achieve a better prognosis. The lack of sensitive and noninvasive biomarkers with clinical utility remains a challenge. Here, we conducted a genome-wide copy number variation (CNV) profiling analysis using low-coverage whole genome sequencing (LC-WGS) of plasma cfDNA in patients with nonmalignant and malignant ovarian tumors and identified 10 malignancy-specific and 12 late-stage-specific CNV markers from plasma cfDNA LC-WGS data. Concordance analysis indicated a significant correlation of identified CNV markers between CNV profiles of plasma cfDNA and tissue DNA (Pearson's r = 0.64, P = 0.006 for the TCGA cohort and r = 0.51, P = 0.04 for the Dariush cohort). By leveraging these specific CNV markers and machine learning algorithms, we developed robust predictive models showing excellent performance in distinguishing between malignant and nonmalignant ovarian tumors with F1-scores of 0.90 and ranging from 0.75 to 0.99, and prediction accuracy of 0.89 and ranging from 0.66 to 0.98, respectively, as well as between early- and late-stage ovarian tumors with F1-scores of 0.84 and ranging from 0.61 to 1.00, and prediction accuracy of 0.82 and ranging from 0.63 to 0.96 in our institute cohort and other external validation cohorts. Furthermore, we also discovered and validated certain CNV features associated with survival outcomes and platinum-based chemotherapy response in multicenter cohorts. In conclusion, our study demonstrated the clinical utility of CNV profiling in plasma cfDNA using LC-WGS as a cost-effective and accessible liquid biopsy for OV.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Ovarianas , Humanos , Feminino , Variações do Número de Cópias de DNA/genética , Diagnóstico Diferencial , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Prognóstico , Ácidos Nucleicos Livres/genética , Biomarcadores Tumorais/genética
6.
Langmuir ; 39(22): 7766-7774, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37228013

RESUMO

Water reclamation is the most effective way to continuously provide clean water to combat catastrophic global water scarcity. However, current technology for water purification is not conducive to sustainability due to the high energy consumption and negative environmental impact. Here, we introduce an innovative method by utilizing the hierarchical microstructure of bamboo for water purification. Natural bamboo was delignified followed by freeze-drying to obtain a bamboo aerogel with a porosity of 72.0%; then, the bamboo aerogel was coated with silver nanoparticles to form a hierarchical bamboo/silver nanoparticle composite. The scanning electron microscopy images and energy-dispersive X-ray spectroscopy results indicated that the silver nanoparticles were uniformly attached to the parenchyma cell surface. By physical adsorption and catalytic reduction, the bamboo/silver nanoparticle composite was able to degrade methylene blue by more than 96.7%, which is mainly attributed to the large specific surface area of the bamboo providing more space for the purification reaction. This composite can be potentially used for board applications with its high porosity, mechanical reliability, and sustainability.

7.
Adv Mater ; 35(17): e2210879, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36786375

RESUMO

Efficient therapeutic strategies that concurrently target both Aß aggregation and oxidative stress in the Alzheimer's disease (AD) microenvironment emerge as a cutting-edge tool to combat the intricate pathogenesis of AD. Here, a multivalent nanobody conjugate with rigid, reactive oxygen species (ROS) scavenging scaffold is developed to achieve simultaneous Aß amyloidogenesis mitigation, ROS elimination, and Aß plaque clearance. Grafting Aß segment (33-GLMVGGVVIA-42) into the third complementary-determining region of a parent nanobody generates an engineered nanobody NB that can recognize Aß and inhibit its aggregation through homotypic interactions. NB is further genetically modified with a fragment of human interleukin-1ß (163-VQGEESNDK-171), so that the obtained fusion nanobody NBIL can also facilitate the Aß clearance by microglia. Linking NBIL covalently onto a rigid, ROS scavenging scaffold poly(deca-4,6-diynedioic acid) (PDDA) creates the multivalent nanobody conjugate PNBIL, which not only boosts the binding affinity between NBIL and Aß aggregates for nearly 100 times but also possesses a long-term capability of oxidative stress alleviation, inflammation reduction, and neuron protection. PNBIL has significantly attenuated symptoms on two AD mouse models through amyloidogenesis inhibition and AD microenvironment modulation, validating that the multivalent nanobody conjugate design based on combinatory nanobody and molecular engineering is a promising approach of multi-target therapeutic strategies.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Estresse Oxidativo
8.
ACS Nano ; 17(4): 3873-3888, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36791326

RESUMO

Accurate diagnosis and timely therapeutic intervention of inflammatory bowel disease (IBD) is essential in preventing the progression of the disease, although it still represents an insurmountable challenge. Here we report the design of bacterial-flagella-inspired polydiiododiacetylene (PIDA) nanofibers and its performance in targeted computed tomography (CT) imaging and on-demand therapeutic intervention of IBD. With a morphology mimicking bacterial flagella, PIDA nanofibers attach on the mucus layer of the gastrointestinal (GI) tract after oral administration, evenly distributing on the GI surface to portray the GI lining under CT scan within 2 h. PIDA can retain for a longer time in the damaged mucosa at the inflamed lesions than in normal GI tissues to enable the targeted CT visualization of IBD. PIDA also scavenges reactive oxygen species and ameliorates gut dysbiosis attributed to its iodine-substituted polydiacetylene structure, so that the enriched PIDA nanofibers at the targeted IBD lesions can alleviate the inflammation while maintaining the gut microbiota homeostasis, thus promoting the rebalance of GI microenvironment and the mucosal healing.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Nanofibras , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inflamação , Tomografia Computadorizada por Raios X
9.
J Adv Res ; 44: 149-160, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36725186

RESUMO

INTRODUCTION: Increasing evidence demonstrates that the activation states and diverse spectrum of macrophage subtypes display dynamic heterogeneity in the tumor microenvironment, which plays a critical role in a variety of cancer types. OBJECTIVES: To investigate the heterogeneity and the homeostasis of different macrophage subtypes, as well as their effect on biological and clinical manifestations of ovarian cancer (OV). METHOD: Integrated immunogenomic analysis of single-cell and bulk tissuetranscriptome profiling was performed to systematically investigate the association between macrophage activation and prognostic and therapeutic efficacy. Consensus clustering analysis was used to define novel macrophage subtypes. An artificial neural network was used to simulate the dynamic activation of macrophages. RESULTS: The pan-cohort results suggested that high relative infiltration abundance of M0 and M1 macrophages was associated with improved outcome and therapeutic efficacy. However, it was the opposite for M2 macrophages. Unsupervised consensus clustering analysis revealed two OV subgroups characterized by a balance between M0, M1 and M2 macrophages with distinct clinical and immunological behaviors. Finally, a macrophage polarization-derived artificial neural network model was proposed to serve as a robust prognostic factor and predictive biomarker for therapeutic efficacy, which was validated in different independent patient cohorts. CONCLUSION: The present study provides a new understanding of macrophage heterogeneity and its association with OV prognosis and underlines the future clinical potential of a macrophage activation model for tumor prevention and treatment.


Assuntos
Ativação de Macrófagos , Neoplasias Ovarianas , Humanos , Feminino , Macrófagos , Transcriptoma , Perfilação da Expressão Gênica , Neoplasias Ovarianas/genética , Microambiente Tumoral
10.
Cell Death Dis ; 13(12): 1040, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517470

RESUMO

Ferroptosis is a recently-defined tumor suppression mechanism, but the sensitivity of many tumorigenic cells to ferroptosis is limited by their deficient expression of acyl-CoA synthetase long-chain family member 4 (ACSL4). Here, we report the discovery of a photosensitizer, namely TPCI, which can evoke ACSL4-independent ferroptosis of cancer cells in photodynamic therapy. Through co-localization with 12-lipoxygenase (ALOX12) in multiple subcellular organelles, TPCI activates ALOX12 to generate lipid reactive oxygen species in large quantity and trigger cell ferroptosis. Intriguingly, confining TPCI exclusively in lysosomes switches the cell death from ferroptosis to apoptosis. More strikingly, the ferroptosis mediated by TPCI-induced ALOX12 activation does not require the participation of ACSL4. Therefore, our study identifies TPCI as the first ALOX12 activator to induce ferroptosis independent of ACSL4, which renders a viable therapeutic approach on the basis of distinct ferroptosis of cancer cells, regardless their ACSL4 expressions.


Assuntos
Ferroptose , Fármacos Fotossensibilizantes/farmacologia , Coenzima A Ligases/metabolismo , Apoptose , Organelas/metabolismo
11.
Biosensors (Basel) ; 12(11)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36354468

RESUMO

Nanotechnology has attracted much attention, and may become the key to a whole new world in the fields of food, agriculture, building materials, machinery, medicine, and electrical engineering, because of its unique physical and chemical properties, including high surface area and outstanding electrical and optical properties. The bottom-up approach in nanofabrication involves the growth of particles, and we were inspired to propose a novel nanoplasmonic method to detect the formation of nanoparticles in real time. This innovative idea may contribute to the promotion of nanotechnology development. An increase in nanometer particle size leads to optical extinction or density (OD)-value changes in our nanosensor chip at a specific wavelength measured in a generic microplate reader. Moreover, in applying this method, an ultrasensitive nanoplasmonic immunoturbidimetry assay (NanoPITA) was carried out for the high-throughput quantification of hypersensitive C-reactive protein (CRP), a well-known biomarker of cardiovascular, inflammatory, and tumor diseases. The one-step detection of the CRP concentration was completed in 10 min with high fidelity, using the endpoint analysis method. The new NanoPITA method not only produced a linear range from 1 ng/mL to 500 ng/mL CRP with the detection limit reduced to 0.54 ng/mL, which was an improvement of over 1000 times, with respect to regular immunoturbidity measurement, but was also effective in blood detection. This attractive method, combined with surface plasmon resonance and immunoturbidimetry, may become a new technology platform in the application of biological detection.


Assuntos
Técnicas Biossensoriais , Proteína C-Reativa , Proteína C-Reativa/análise , Imunoturbidimetria , Ressonância de Plasmônio de Superfície/métodos , Nanotecnologia/métodos , Biomarcadores , Técnicas Biossensoriais/métodos
12.
Artigo em Inglês | MEDLINE | ID: mdl-36301911

RESUMO

Two-dimensional (2D) nanomaterials hold great potential for cancer theranostic applications, yet their clinical translation faces great challenges of high toxicity and limited therapeutic/diagnostic modality. Here, we have created a kind of symbiotic 2D carbon-2D clay nanohybrids, which are composed of a novel 2D carbon nanomaterial (carbon nanochips, or CNC), prepared by carbonizing a conjugated polymer polydiiodobutadiyne, and a 2D layered aluminosilicate clay mineral montmorillonite (MMT). Intriguingly, with the formation of the nanohybrids, MMT can help the dispersion of CNC, while CNC can significantly reduce the hemolysis and toxicity of MMT. The symbiotic combination of CNC and MMT also leads to a synergistic anti-cancer theranostic effect. CNC has a strong absorption and high photothermal conversion efficiency in the second near-infrared region (NIR-II, 1000-1700 nm), while MMT contains Fe3+ that can facilitate the generation of reactive oxygen species from highly expressed H2O2 in tumor microenvironment. The nanohybrids not only enable a synergy of photothermal therapy and chemodynamic therapy to suppress the extremely rapid growth of RM1 tumors in mice but also allow for dual photoacoustic and magnetic imaging to guide the drug delivery and NIR-II irradiation execution, hence establishing a highly efficient and biosafe "all-in-one" theranostic platform for precision nanomedicine.

13.
Nat Commun ; 13(1): 4553, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931666

RESUMO

Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically "cold" tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Hidrogéis , Camundongos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
14.
Nano Lett ; 22(11): 4544-4551, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35604007

RESUMO

Raman-based super multiplexing has attracted great interest in imaging, biological analysis, identity security, and information storage. It still remains a great challenge to synthesize a large number of different Raman-active molecules to fulfill the Raman color palette. Here, we report a facile and systematic strategy to construct continuously multiplexed ultrastrong Raman probes. By precisely incorporating different ratios of 13C isotope into the backbone of poly(deca-4,6-diynedioic acid) (PDDA), we can obtain a library of PDDAs with tunable double-bond Raman frequencies and adjustable intensity ratios of two triple-bond (13C≡13C and 12C≡12C) Raman peaks, while retaining the ultrastrong Raman signals and physicochemical properties of the polymer. We also demonstrate the successful application of 13C-doped PDDAs as security inks to generate a novel 3D matrix barcode system for information encryption and high-density data storage. The isotopically doped PDDA series herein pave a new way to advance Raman-based super multiplexing for diverse applications.


Assuntos
Polímeros , Análise Espectral Raman , Armazenamento e Recuperação da Informação , Análise Espectral Raman/métodos
15.
Nat Commun ; 13(1): 2625, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551194

RESUMO

X-ray computed tomography (CT) has an important role in precision medicine. However, CT contrast agents with high efficiency and the ability to translate diagnostic accuracy into therapeutic intervention are scarce. Here, poly(diiododiacetylene) (PIDA), a conjugated polymer composed of only carbon and iodine atoms, is reported as an efficient CT contrast agent to bridge CT diagnostic imaging with therapeutic intervention. PIDA has a high iodine payload (>84 wt%), and the aggregation of nanofibrous PIDA can further amplify CT intensity and has improved geometrical and positional stability in vivo. Moreover, with a conjugated backbone, PIDA is in deep blue color, making it dually visible by both CT imaging and the naked eyes. The performance of PIDA in CT-guided preoperative planning and visualization-guided surgery is validated using orthotopic xenograft rat models. In addition, PIDA excels clinical fiducial markers of imaging-guided radiotherapy in efficiency and biocompatibility, and exhibits successful guidance of robotic radiotherapy on Beagles, demonstrating clinical potential to translate CT diagnosis accuracy into therapeutic intervention for precision medicine.


Assuntos
Iodo , Animais , Carbono , Cães , Humanos , Imagens de Fantasmas , Polímeros , Ratos , Tomografia Computadorizada por Raios X/métodos
16.
Macromol Rapid Commun ; 43(18): e2200194, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35578790

RESUMO

Despite being the mainstay treatment for many types of cancer in clinic, radiotherapy is undertaking great challenges in overcoming a series of limitations. Radiosensitizers are promising agents capable of depositing irradiation energy and generating free radicals to enhance the radiosensitivity of tumor cells. Combining radiosensitizers with functional polymer-based nanomaterials holds great potential to improve biodistribution, circulation time, and stability in vivo. The derived polymeric nano-radiosensitizers can significantly improve the efficiency of tumor targeting and radiotherapy, and reduce the side effect to healthy tissues. In this review, an overview of functional polymer-based nanomaterials for radiosensitization in recent years is provided. Particular emphases are given to the action mechanisms, drug loading methods, targeting efficiencies, the impact on therapeutic effects, and biocompatibility of various radiosensitizing polymers, which are classified as polymeric micelles, dendrimers, polymeric nanospheres, nanoscale coordination polymers, polymersomes, and nanogels. The challenges and outlooks of polymeric nano-radiosensitizers are also discussed.


Assuntos
Dendrímeros , Nanoestruturas , Neoplasias , Radiossensibilizantes , Humanos , Micelas , Nanogéis , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Polímeros/uso terapêutico , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Distribuição Tecidual
17.
Transl Cancer Res ; 11(2): 414-425, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35281418

RESUMO

Background: Tripartite motif-containing protein 44 (TRIM44) was recently identified as a novel oncogene that is overexpressed in several types of human cancers. However, the biological functions of TRIM44 in epithelial ovarian cancer (EOC) remain unclear. Here, we aimed to investigate the role of TRIM44 in EOC and its clinical implications. Methods: TRIM44 was knocked down using shRNA transfection. In vitro proliferation, invasion, migration and apoptosis of ovarian cancer (OC) cells were detected by CCK8, colony formation assay, Transwell inserts and flow cytometry analysis. The growth ability of xenograft tumors was examined in vivo in a nude mouse metastatic tumor model. Finally, we performed gene chip analysis and ingenuity pathway analysis (IPA) to analyze the potential gene network. Results: High expression of TRIM44 was observed in EOC tissues. Knockdown of TRIM44 expression substantially suppressed the proliferation, migration, invasion and colony-forming ability of EOC cells in vitro and attenuated tumor growth in vivo. Mechanistic studies revealed that silencing TRIM44 dramatically downregulated the expression of FOXM1, EZH2, CCNE2, CCND3 and BIRC5 in EOC cells, at least in part through inactivation of the FOXM1-EZH2 signaling pathway. Conclusions: Collectively, these data suggest that downregulation of TRIM44 inhibits the progression of EOC through suppression of the FOXM1-EZH2 signaling pathway. These results provide novel insight into the role of TRIM44 in tumorigenesis and suggest that it could be a potential therapeutic target for ovarian carcinoma.

18.
Oncologist ; 27(1): e64-e75, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35305106

RESUMO

BACKGROUND: The glioblastoma-amplified sequence (GBAS) is a newly identified gene that is amplified in approximately 40% of glioblastomas. This article probes into the expression, prognostic significance, and possible pathways of GBAS in ovarian cancer (OC). METHOD: Immunohistochemical methods were used to evaluate the expression level of GBAS in OC and its relationship with clinicopathological characteristics and prognosis. Glioblastoma-amplified sequence shRNA was designed to transfect into OC cell lines to silence GBAS expression, then detect the proliferation, apoptosis, and migration ability of the cell. Furthermore, an in vitro tumor formation experiment in mice was constructed to prove the effect of GBAS expression on the growth of OC in vivo. To further study the regulation mechanism of GBAS, we performed co-immunoprecipitation (Co-IP) and shotgun LC-MS mass spectrometry identification. RESULTS: Immunohistochemistry indicated that GBAS was markedly overexpressed in OC compared with normal ovarian tissue and was associated with lymph node metastasis. Inhibition of GBAS expression can significantly reduce OC cell proliferation, colony formation, promote cell apoptosis, and reduce the ability of cell migration and invasion. In vivo tumor formation experiments showed that the size and weight of tumors in mice after GBAS expression knockdown was significantly smaller. Glioblastoma-amplified sequence may be combined with elongation factor 1 alpha 1 (eEF1A1) to achieve its regulation in OC. Bioinformatics analysis data indicate that GBAS may be a key regulator of mitochondria-associated pathways, therefore controlling cancer progression. MicroRNA-27b, MicroRNA-23a, and MicroRNA-590 may directly targeting GBAS affects the biological behavior of OC cells. CONCLUSION: The glioblastoma-amplified sequence may regulate the proliferation and metastasis of OC cells by combining with eEF1A1.


Assuntos
Glioblastoma , MicroRNAs , Neoplasias Ovarianas , Animais , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Humanos , Camundongos , MicroRNAs/genética , Neoplasias Ovarianas/patologia , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/metabolismo
19.
Nanoscale ; 14(7): 2802-2815, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35133388

RESUMO

The misfolding and aggregation of human islet amyloid polypeptide (IAPP) into ß-sheet-enriched amyloid fibrils is linked to type 2 diabetes. Antibodies are potent inhibitors of IAPP amyloidogenesis, but their preparation is usually complicated and expensive. Here we have created a multivalent antibody mimic SPEPS@Au through conformational engineering of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs). By immobilizing both terminals of an IAPP-recognizing CDR loop (PEP) on the surface of AuNPs, the active conformation of PEP can simply recur on the gold-based antibody mimic, significantly enhancing the binding affinity between PEP and IAPP. SPEPS@Au mitigated amyloidogenesis of IAPP at low sub-stoichiometric concentrations, even after IAPP started aggregating, and dramatically reduced the amyloidogenesis-induced toxicity and ROS production both in vitro and in vivo. The conformation-reconstructed multivalent antibody mimic not only renders a facile strategy to approach potent amyloidogenesis inhibitors, but also provides new perspectives to exploit NP-based substitutes for antibodies in various applications.


Assuntos
Diabetes Mellitus Tipo 2 , Ilhotas Pancreáticas , Nanopartículas Metálicas , Amiloide/química , Diabetes Mellitus Tipo 2/metabolismo , Ouro/metabolismo , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Ilhotas Pancreáticas/metabolismo
20.
Nanotechnology ; 33(20)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35078166

RESUMO

Metal-organic frames (MOFs) are regarded as excellent candidates for supercapacitors that have attracted much attention because of their diversity, adjustability and porosity. However, both poor structural stability in aqueous alkaline electrolytes and the low electrical conductivity of MOF materials constrain their practical implementation in supercapacitors. In this study, bimetallic CoNi-MOF were synthesized to enhance the electrical conductivity and electrochemical activity of nickel-based MOF, as well as the electrochemical performance of the CoNi-MOF in multiple alkaline electrolytes was investigated. The CoNi-MOF/active carbon device, as-fabricated with a 1 M KOH electrolyte, possesses a high energy density of 35 W h kg-1with a power density of 1450 W kg-1, exhibiting outstanding cycling stability of 95% over 10,000 cycles. The design of MOF-based electrode materials and the optimization selection of electrolytes pave the way for constructing high-performance supercapacitors.

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