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1.
Environ Toxicol ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682322

RESUMEN

OBJECTIVE: Polyunsaturated fatty acids (PUFAs) have attracted increasing attention for their role in liver cancer development. The objective of this study is to develop a prognosis prediction model for patients with liver cancer based on PUFA-related metabolic gene characteristics. METHOD: Transcriptome data and clinical data were obtained from public databases, while gene sets related to PUFAs were acquired from the gene set enrichment analysis (GSEA) database. Univariate Cox analysis was conducted on the training set, followed by LASSO logistic regression and multivariate Cox analysis on genes with p < .05. Subsequently, the stepwise Akaike information criterion method was employed to construct the model. The high- and low-risk groups were divided based on the median score, and the model's survival prediction ability, diagnostic efficiency, and risk score distribution of clinical features were validated. The above procedures were also validated in the validation set. Immune infiltration levels were evaluated using four algorithms, and the immunotherapeutic potential of different groups was explored. Significant enrichment pathways among different groups were selected based on the GSEA algorithm, and mutation analyses were conducted. Nomogram prognostic models were constructed by incorporating clinical factors and risk scores using univariate and multivariate Cox regression analysis, validated through calibration curves and clinical decision curves. Additionally, sensitivity analysis of drugs was performed to screen potential targeted drugs. RESULTS: We constructed a prognostic model comprising eight genes (PLA2G12A, CYP2C8, ABCCI, CD74, CCR7, P2RY4, P2RY6, and YY1). Validation across multiple datasets indicated the model's favorable prognostic prediction ability and diagnostic efficiency, with poorer grading and staging observed in the high-risk group. Variations in mutation status and pathway enrichment were noted among different groups. Incorporating Stage, Grade, T.Stage, and RiskScore into the nomogram prognostic model demonstrated good accuracy and clinical decision benefits. Multiple immune analyses suggested greater benefits from immunotherapy in the low-risk group. We predicted multiple targeted drugs, providing a basis for drug development. CONCLUSION: Our study's multifactorial prognostic model across multiple datasets demonstrates good applicability, offering a reliable tool for personalized therapy. Immunological and mutation-related analyses provide theoretical foundations for further research. Drug predictions offer important insights for future drug development and treatment strategies. Overall, this study provides comprehensive insights into tumor prognosis assessment and personalized treatment planning.

2.
ACS Appl Mater Interfaces ; 15(46): 53318-53332, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37943829

RESUMEN

Despite immunotherapy having revolutionized cancer therapy, the efficacy of immunotherapy in triple-negative breast cancer (TNBC) is seriously restricted due to the insufficient infiltration of mature dendritic cells (DCs) and the highly diffusion of immunosuppressive cells in the tumor microenvironment. Herein, an immunomodulatory nanoplatform (HA/Lipo@MTO@IMQ), in which the DCs could be maximally activated, was engineered to remarkably eradicate the tumor via the combination of suppressive tumor immune microenvironment reversal immunotherapy, chemotherapy, and photothermal therapy. It was noticed that the immunotherapy efficacy could be significantly facilitated by this triple-assistance therapy: First, a robust immunogenic cell death (ICD) effect was induced by mitoxantrone hydrochloride (MTO) to boost DCs maturation and cytotoxic T lymphocytes infiltration. Second, the powerful promaturation property of the toll-like receptor 7/8 (TLR7/8) agonist on DCs simultaneously strengthened the ICD effect and restricted antitumor immunity to the tumor bed and lymph nodes. On this basis, tumor-associated macrophages were also dramatically repolarized toward the antitumor M1 phenotype in response to TLR7/8 agonist to intensify the phagocytosis and reverse the immunosuppressive microenvironment. Furthermore, the recruitment of immunocompetent cells and tumor growth inhibition were further promoted by the photothermal characteristic. The nanoplatform with no conspicuous untoward effects exhibited a splendid ability to activate the systemic immune system so as to increase the immunogenicity of the tumor microenvironment, thus enhancing the tumor killing effect. Taken together, HA/Lipo@MTO@IMQ might highlight an efficient combination of therapeutic modality for TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Terapia Fototérmica , Receptor Toll-Like 7 , Microambiente Tumoral , Factores Inmunológicos , Adyuvantes Inmunológicos , Inmunosupresores , Inmunoterapia , Línea Celular Tumoral
3.
Nanoscale ; 15(40): 16314-16322, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37786260

RESUMEN

Recently, disulfiram (DSF), an anti-alcoholism drug, has attracted increasing biomedical interest due to its anticancer effects. However, the anticancer activity of DSF is Cu(II)-dependent and it is extremely unstable, which severely hinders its clinical translation. Herein, we report the fabrication of a multifunctional nanoplatform (MCDGF) that can improve the stability of diethyldithiocarbamate (DTC), a main metabolite of DSF, by modifying the aryl boronic ester group to form a prodrug (DQ), and also realize the in situ generation of Cu(DTC)2, which relies on a cascade reaction. The delivered Cu/DQ induces immunogenic cell death (ICD) and powerfully enhances immune responses of cytotoxic T lymphocytes (CTLs) and the infiltration of dendritic cells as well as T cells. Furthermore, the grafted glucose oxidase (GOx) decomposes glucose, thus "starving" the cancer cells and providing H2O2 for the production of Cu(DTC)2. More importantly, H2O2 significantly promotes the polarization of macrophages to the anti-tumor subtype. The nano-carrier "mesoporous polydopamine (MPDA)" also displays a good photothermal therapeutic effect. The nanoplatform-integrated chemotherapy, starvation therapy, photothermal therapy, and immunotherapy synergistically stimulated CTL activation and M1 macrophage polarization. Taken together, the as-prepared nanoplatform could regulate the tumor immune microenvironment and eliminate cancer with combined cancer therapy, which will offer a promising strategy for cancer treatment and promote the clinical application of DSF in breast cancer.


Asunto(s)
Neoplasias de la Mama , Neoplasias , Humanos , Femenino , Microambiente Tumoral , Peróxido de Hidrógeno/metabolismo , Línea Celular Tumoral , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Disulfiram/farmacología , Neoplasias/tratamiento farmacológico , Cobre
4.
BMC Cancer ; 23(1): 364, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37081411

RESUMEN

Homo sapiens chromosome 2 clone RP11-339H12 (AC010883.5) is a dysregulated long non-coding RNA (lncRNA) that has never been investigated in cervical cancer (CC). Thus, the potential function and molecular mechanism remain unclear. Our study explored the biological function of AC010883.5 to determine the underlying mechanisms in CC and provide potential therapeutic targets for improving the clinical treatment strategy. We used quantitative real-time polymerase chain reaction to measure mitochondrial RNA levels and western blot to measure the protein levels of target genes. Further, we used Cell Counting Kit-8 and 5-Bromo-2'-deoxyuridine incorporation assays to evaluate cell proliferation in vitro. Cell apoptosis was analyzed by flow cytometry. Cell invasion was analyzed by wound healing and Transwell migration assays was ued to analyze cell migration. Finally, the biological function and mechanism of AC010883.5 in CC growth were evaluated by in vivo xenograft assay. AC010883.5 was enhanced in CC tissues and cell lines, and enhanced AC010883.5 expression accelerated CC cell proliferation, migration, and invasion and induced epithelial-mesenchymal transition in vitro and in vivo. AC010883.5 also activated the mitogen-activated protein kinase (MAPK) signaling pathway by promoting phosphorylation of extracellular signal-regulated kinase 1/2 (i.e., ERK1/2) and MAPK kinase 1/2 (i.e., MEK1/2). Blocking the MAPK signaling pathway could counteract the pro-proliferative, pro-migrative, and pro-invasive effects of AC010883.5 over-expression. We found that the lncRNA, AC010883.5, is an oncogenic molecule involved in CC tumor progression via dysregulation of the MAPK signaling pathway, implying that AC010883.5 could be a tumor progression and therapeutic response biomarker.


Asunto(s)
ARN Largo no Codificante , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Línea Celular Tumoral , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transición Epitelial-Mesenquimal/genética , Transducción de Señal , Proliferación Celular/genética , Procesos Neoplásicos , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica
5.
Int J Clin Pract ; 2023: 2291156, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36974156

RESUMEN

Objective: Endometriosis, which is a common disease affecting approximately 10% of women of reproductive age, usually causes dysmenorrhea and infertility, thus seriously harming the patients' physical and mental health. However, there is a mean delay of 6.7 years between the onset of the symptoms and the surgical diagnosis of endometriosis. There is an increasing amount of evidence that suggests that epigenetic aberrations, including deoxyribonucleic acid (DNA) methylation, play a definite role in the pathogenesis of endometriosis. This study aimed to explore the noninvasive or minimally invasive biomarkers of this disease. Materials and Methods: Six patients with surgically confirmed ovarian endometriosis and six patients who received IUD implantation for contraception without endometriosis were recruited in the East Hospital of Tongji University in 2018. The genome methylation profiling of the eutopic and ectopic endometrium of ovarian endometriosis patients and normal endometrial specimens from healthy women was determined using a methylation microarray test. The test screened methylation-differentiated 5'-C-phosphate-G-3' (CpG) sites and then located the target genes affected by these sites following sequence alignment. Then, an additional 22 patients and 26 healthy controls were enrolled to further verify the difference in the selected genes between endometriosis patients and healthy women. The differential DNA methylation of the selected genes was validated via direct bisulfite sequencing and analysis of their messenger ribonucleic acid (mRNA) levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: Fifteen differentially methylated CpG sites were found among the patients and healthy women, and five CpG sites were mapped to the introns of the human leukocyte antigen-C (HLA-C) gene; these were highly polymorphic between different HLA-C alleles and were HLA-C∗07 specific. The results indicated that the HLA-C∗07 carrier patients exhibited significantly higher DNA methylation levels at the intron VII of HLA-C compared to the HLA-C∗07 carrier healthy controls. High HLA-C∗07 mRNA levels were also observed using qRT-PCR with HLA-C∗07-specific primers, which indicated that the hypermethylation of CpG in intron VII might suppress a silencer that regulates HLA-C∗07 expressions. Conclusion: Deoxyribonucleic acid hypermethylation in the intron VII of the HLA-C∗07 gene appears to regulate the expression of HLA-C∗07. The aberrant DNA methylation in this region was positively correlated with the occurrence of endometriosis.


Asunto(s)
Metilación de ADN , Endometriosis , Humanos , Femenino , Metilación de ADN/genética , Endometriosis/genética , Endometriosis/metabolismo , Intrones/genética , Antígenos HLA-C/genética , Antígenos HLA-C/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ADN/metabolismo
6.
ACS Appl Mater Interfaces ; 14(32): 36503-36514, 2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-35925873

RESUMEN

Ovarian cancer has become an urgent threat to global female healthcare. Cisplatin, as the traditional chemotherapeutic agent against ovarian cancer, retains several limitations, such as drug resistance and dose-limiting toxicity. In order to solve the above problems and promote the therapeutic effect of chemotherapy, combining chemotherapy and phototherapy has aroused wide interest. In this study, we constructed a versatile cisplatin prodrug-conjugated therapeutic platform based on ultrasmall CuS-modified Fe(III)-metal-organic frameworks (MIL-88) (named M-Pt/PEG-CuS) for tumor-specific enhanced synergistic chemo-/phototherapy. After intravenous injection, M-Pt/PEG-CuS presented obvious accumulation in tumor and Fe(III)-MOFs possessed magnetic resonance imaging (MRI) to guide synergy therapy. Both in vitro and in vivo experimental results showed that M-Pt/PEG-CuS could not only successfully inhibit tumor growth by combining chemotherapy and NIR-II PTT but also avoid the generation of liver damage by the direct treatment of cisplatin(II). Our work presented the development of the nanoplatform as a novel NIR-II photothermal agent, as well as gave a unique combined chemo-photothermal therapy strategy, which might provide new ways of ovarian cancer therapy for clinical translation.


Asunto(s)
Nanopartículas , Neoplasias Ováricas , Profármacos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Doxorrubicina/farmacología , Femenino , Compuestos Férricos , Humanos , Imagen por Resonancia Magnética , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/tratamiento farmacológico , Fototerapia , Terapia Fototérmica , Profármacos/farmacología
7.
Front Immunol ; 12: 682262, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34305915

RESUMEN

Immunotherapy begins to be widely used due to the increasing exploration and gratifying effects in multiple cancers. Chordoma, as a rare bone malignant tumor, often recurs and metastasizes after undergoing surgery and radiotherapy. Therefore, immunotherapy can be explored as an emerging, potentially effective treatment to improve the survival rate and clinical benefit of patients. However, a variety of immune-related adverse events (irAEs) cannot be avoided completely. And the immunotherapy-induced myocarditis, as a rare but fatal irAE, has been increasingly reported. Understanding the mechanism involved in irAEs can inform best practices for side effects management. Here, we firstly reported a case of immune myocarditis and subsequent myasthenia gravis (MG) following anti-PD-1 treatment for chordoma.


Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Cordoma/complicaciones , Miastenia Gravis/complicaciones , Miocarditis/diagnóstico , Miocarditis/etiología , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores , Cordoma/diagnóstico , Cordoma/tratamiento farmacológico , Pruebas de Función Cardíaca , Humanos , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Masculino , Terapia Molecular Dirigida/efectos adversos , Miocarditis/tratamiento farmacológico , Tomografía de Emisión de Positrones , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores
8.
Chem Commun (Camb) ; 57(34): 4158-4161, 2021 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-33908477
9.
Langmuir ; 37(10): 3130-3138, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33657799

RESUMEN

Cationic magnetic Gemini surfactants (mag-G-surfs), [C14H29(CH3)2N(CH2)2N(CH3)2C14H29]2+·2[XCl3Br]- (14-2-14·2X, X = Ce, Gd, or Ho), efficiently induce the aggregation of glutathione-protected Au nanoclusters (NCs) (GSH-Au NCs). These magnetic luminescent aggregates not only possess aggregation-induced emission (AIE) behavior but also display aggregation-induced magnetic enhancement. In particular, 14-2-14·2Ce and 14-2-14·2Gd have a better effect on boosting the luminescence intensity, quantum yield (QY), and luminescence lifetime (τ). The luminescent aggregates of GSH-Au NCs triggered by 14-2-14·2Gd or 14-2-14·2Ho exhibit more favorable paramagnetic behavior. Other Au NCs containing a Au(I)-thiolate complex shell also exhibit the obvious AIE phenomenon after introducing 14-2-14·2Gd, demonstrating the luminescence enhancement effect of mag-G-surfs. The luminescent aggregate 14-2-14·2Ce@GSH-Au NCs can serve as a "light up" fluorometric probe to detect cysteine selectively with the detection limit (DL) of 36 µM, and the magnetic luminescent aggregate 14-2-14·2Gd@GSH-Au NCs has the potential to be a novel contrast agent in T1-weighted magnetic resonance (MR) imaging due to its satisfactory contrasting ability.

10.
Small ; 17(13): e2007051, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33599061

RESUMEN

Immune checkpoint inhibitor (ICI) therapy is considered to be a revolutionary anti-tumor strategy that may surpass other traditional therapies. Breast cancer is particularly suitable for it theoretically due to upregulation of programmed cell death 1 (PD-1) / programmed cell death ligand 1 (PD-L1) immune checkpoint pathway which exhausts the adaptive immune response mediated by T lymphocytes. However, its blockades exhibit very little effect in breast cancer, owing to the lack of T lymphocytes pre-infiltration and co-existing of intricate immune negative microenvironment including the macrophage-suppressed "Don't eat me" CD47 signal overexpression. Herein, a stimuli-responsive multifunctional nanoplatform (ZIF-PQ-PDA-AUN) is built. Its photothermal therapy can promote the infiltration of T lymphocytes in addition to ablating tumor cells and AUNP-12 and PQ912 further boost both the innate and adaptive immune reactions by cutting off PD-L1 and CD47 signals, respectively. In contrast to earlier single immunotherapy, the nanocomposites exhibit a stronger anti-tumor immune effect without obvious autoimmune side effects, promoting infiltration of T lymphocyte into the tumor site and strengthening phagocytosis of macrophages, even more exciting, significantly reversing pro-tumor M2-like tumor-associated macrophages (TAMs) to anti-tumor M1-like TAMs. The research may provide a promising strategy to develop high-efficient and low-toxic immunotherapy based on nanotechnology.


Asunto(s)
Neoplasias de la Mama , Inhibidores de Puntos de Control Inmunológico , Neoplasias de la Mama/terapia , Femenino , Humanos , Inmunoterapia , Fagocitosis , Terapia Fototérmica , Microambiente Tumoral
11.
Chemistry ; 26(7): 1668-1675, 2020 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-31814171

RESUMEN

Despite drug delivery nanoplatforms receiving extensive attention, development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. Herein, a versatile nanoplatform based on a zirconium framework (UiO-66-N3 ) was synthesized, which demonstrated a combined photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy (CT) for cancer treatment. A RuII polypyridyl alkyne complex (Ra) as a photosensitizer was modified into a nanoplatform by click reactions for the first time. When exposed to suitable light irradiation, the as-prepared multifunctional nanoplatform (UiO-Ra-DOX-CuS) not only demonstrated efficient 1 O2 generation, but also exhibited excellent photothermal conversion ability. In particular, the nanotherapeutic agent presented a dual-stimuli response; either acidic environment or NIR laser irradiation would trigger the drug release. The synergetic efficacy of UiO-Ra-DOX-CuS combined PDT, PTT, and CT, which was evaluated by cell experiments. Moreover, the design could promote the development of RuII polypyridyl alkyne complexes based multifunctional nanoparticles and multimodal cancer treatment.


Asunto(s)
Alquinos/farmacología , Fármacos Fotosensibilizantes/farmacología , Compuestos de Rutenio/química , Terapia Combinada , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Quimioterapia Combinada , Humanos , Estructuras Metalorgánicas , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Nanomedicina Teranóstica
12.
Parasit Vectors ; 12(1): 507, 2019 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-31666115

RESUMEN

BACKGROUND: The identification and characterization of epitopes facilitate the discovery and development of new therapeutics, vaccines and diagnostics for infectious diseases. In this study, we developed a glutathione S-transferase (GST)-peptide fusion protein microplate array for the identification of linear B-cell epitopes and applied this novel method to the identification of linear B-cell epitopes of SjSP-13, an immunodiagnostic biomarker of schistosomiasis japonica. METHODS: SjSP-13 was divided into 17 overlapped peptides (p1-17), and the coding sequence of each peptide was obtained by annealing two complementary oligonucleotides. SjSP-13 peptides were expressed by fusion with an N-terminal GST tag and a C-terminal 6xHis tag. The GST-peptide-His fusion protein was specifically bound to the Immobilizer Glutathione MicroWell 96-well plates without purification. SjSP-13 peptides and core epitopes that could be recognized by sera from schistosomiasis patients were identified by ELISA and confirmed by Western blot analysis. The receiver operating characteristic (ROC) analysis was performed to determine the diagnostic validity of the identified peptide. RESULTS: Full-length GST-peptide-His fusion proteins were successfully expressed and specifically bound to the Immobilizer Glutathione MicroWell 96-well plates. Two adjacent peptides (p7 and p8) were found to be highly immunogenic in humans. The core epitope of p7 and p8 is an 11-aa peptide (80KCLDVTDNLPE90) and an 8-aa peptide (90EKIIQFAE97), respectively. The area under the ROC curve (AUC) value of the peptide which contains the two identified epitopes is 0.947 ± 0.019. The diagnostic sensitivity and specificity of the peptide is 76.7% (95% CI: 68.8-84.5%) and 100%, respectively. CONCLUSIONS: 90EKIIQFAE97 and 80KCLDVTDNLPE90 are the two linear epitopes of SjSP-13 recognized by patient sera, and could be potential serological markers for schistosomiasis japonica.


Asunto(s)
Epítopos/análisis , Glutatión Transferasa/inmunología , Proteínas del Helminto/inmunología , Péptidos/inmunología , Schistosoma japonicum/inmunología , Animales , Área Bajo la Curva , Western Blotting , Epítopos/genética , Glutatión Transferasa/química , Glutatión Transferasa/genética , Proteínas del Helminto/genética , Humanos , Biblioteca de Péptidos , Péptidos/química , Péptidos/genética , Análisis por Matrices de Proteínas , Señales de Clasificación de Proteína/genética , Curva ROC , Schistosoma japonicum/genética , Sensibilidad y Especificidad
13.
J Colloid Interface Sci ; 536: 88-97, 2019 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-30359888

RESUMEN

Covalent grafting and electrostatic-driven assembly have been two strategies in constructing well-defined polyoxometalate (POM) assemblies to produce specific morphologies and desirable properties. The modification of anionic counter-ions of amphiphilic compounds in POM-surfactant hybrid systems is still unexploited. Herein, we report the co-assembly of a synthetic double-tailed magnetic surfactant (MagSurf), (C18)2C2N+[FeCl4]-, and POM, {Mo72Fe30}. The magnetic aggregate (POM/MagSurf) results from the building up hierarchical structures at a time-dependent interface. In this construct, both the MagSurfs and {Mo72Fe30} POMs contribute to and mutually strengthen the magnetization of the designed magnetic assembles. Interestingly, the POM/MagSurf aggregates are compatible with aqueous mixtures and successfully employed to serve as magnetic transporting vehicles to anchor and deliver a protein molecule, myoglobin (Mb). Upon applying a magnetic field (0.3 T), the magnetic aggregates induced a directional migration and enrichment of the Mb protein (71-90%). During this process, the protein/POM/MagSurf complexes exhibited strong interactions facilitating stable anchoring and efficient enrichment of the Mb.


Asunto(s)
Hierro/química , Magnetismo , Nanopartículas de Magnetita/química , Molibdeno/química , Proteínas/química , Tensoactivos/química , Compuestos de Tungsteno/química , Tamaño de la Partícula , Propiedades de Superficie
14.
J Cell Biochem ; 119(10): 8112-8122, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29932240

RESUMEN

Our study was aimed to investigate the mechanism of rs4759314 located in HOTAIR involved in congenital heart disease. Luciferase assay was performed to evaluate whether rs4759314 affected the transcription efficiency of HOTAIR promoter, and confirm miR-545 target gene. Real-time PCR, Western-blot and IHC were carried out to investigate the relationship among HOTAIR, EGFR, p-ERK, P-P38 MAPK. MTT assay and flow cytometry analysis were performed to detect the effect of HOTAIR on cell viability and apoptosis. The presence of G allele of the polymorphism located in HOTAIR promoted transcription activity of HOTAIR promoter. Furthermore, HOTAIR inhibited miR-545 expression. EGFR was identified as a virtual target gene of miR-545 using bioinformatics analysis, and miR-545 apparently decreased luciferase activity of wild-type EGFR 3'UTR, while miR-545 had no effect on luciferase activity of mutant EGFR 3'UTR. HOTAIR and EGFR were lowly expressed, while miR-545 was highly expressed in VSD group. Higher levels of HOTAIR and ECFR, while a lower level of miR-545 were observed in AG than AA groups. Regulatory relationships between HOTAIR and miR-545, as well as EGFR and miR-545 were found to be negatively correlated, with the negative correlation coefficient being -0.49 and -0.46, respectively. HOTAIR evidently increased EGFR p-ERK and P-P38 MAPK expression levels, moreover HOTAIR substantially promoted cell viability, and inhibited cell apoptosis. In this study, we suggested the possible relation between the rs4759314 polymorphism and the risk of congenital heart disease, and explored the deregulation of HOTAIR/miR-545/EGFR/MAPK signaling pathway in the pathogenesis of congenital heart disease.


Asunto(s)
Proliferación Celular/fisiología , Polimorfismo Genético/genética , Apoptosis/genética , Apoptosis/fisiología , Western Blotting , Línea Celular , Proliferación Celular/genética , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Genotipo , Humanos , MicroARNs/genética , Regiones Promotoras Genéticas/genética , ARN Largo no Codificante/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
15.
Langmuir ; 34(24): 7171-7179, 2018 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-29809016

RESUMEN

Developing nontoxic artificial carriers for stimuli-responsive capture, transport, and delivery of biomolecules is of immense scientific interest. Herein, for the first time, we synthesize a double-tailed cationic surfactant, (C16H33)2(CH3)2N+[FeCl3Br]-, which possesses magnetic properties [magnetic surfactants (Mag-Surfs)]. The time-dependent formation of virus-shaped hybrid mixed assemblies of polyoxometalates (POMs) {Mo72Fe30}/Mag-Surf with hollow-shell structures is followed. These structures serve well as robust high-surface-area shuttles, which can be manipulated with applied magnetic fields. By using cationic Mag-Surfs, the anionic POMs and DNA can be complexed in these ternary mixtures. These virus-shaped complexes act as nanoanchors and nanomotors, which can be utilized for binding, anchoring, and delivery of biomolecules, such as DNA. It is found that they have a good absorption capacity for DNA and myoglobin over 24 h, after application of a magnetic field. The realization of magnetic virus-shaped {Mo72Fe30}/Mag-Surf spheres may open possibilities for designing other functional nanoparticles, allowing effective control over the delivery/separation of biomolecules.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Magnetismo , Nanopartículas/química , ADN/química , Campos Magnéticos , Tensoactivos/química
16.
Int J Clin Exp Pathol ; 10(12): 11489-11495, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-31966504

RESUMEN

Endometrial carcinoma is one of the most common gynecological malignant tumors. Recent evidence has demonstrated that miR-21 is involved in the proliferation and invasion of endometrial carcinoma. This study aims to explore the effect of biological behavior of miR-21 on endometrial carcinoma its relationship with PTEN. First, Collected endometrial carcinoma and adjacent non-tumor issues, the relative expression levels of miR-21 and PTEN mRNA were quantitated by real-time polymerase chain reaction (RT-PCR). Next, endometrial carcinoma cell line Ishikawa were transfected with miR-21 inhibitor. After transfection, real-time PCR was used to detect the expression levels of miR-21. Then, the cells proliferation, the apoptotic rates and the invasion rates were detected by MTT method, flow cytometry, and Transwell assay. The expression levels of p-PTEN and PTEN proteins were detected by western blot. The results showed that miR-21 was significantly up-regulation and PTEN was down-regulation in endometrial carcinoma tissues (P < 0.05). miR-21 inhibitor were successfully transfected into Ishikawa cell. The cell proliferation activity, and the number invasion cells in the miR-21 inhibitor group was obviously lower than the miR-21 NC group and Normal group (P < 0.05). The apoptosis rate in the miR-21 inhibitor group was significantly higher than the miR-21 NC group and Normal group (P < 0.05). The expression levels of p-PTEN in miR-21 inhibitor groups were significantly higher than miR-21 NC group and Normal group (P < 0.05). Therefore, we concluded that miR-21 could promote cell proliferation and invasion ability, and inhibite cell apoptosis in endometrial carcinoma partially by regulating its target gene PTEN on post-transcriptional level. In brief, miR-21 may be a new early diagnosis mark and therapy target in endometrial carcinoma.

17.
Langmuir ; 32(40): 10226-10234, 2016 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-27636012

RESUMEN

Bacillus-shaped bilayer vesicles of nanoscale size are very rare structures of stable surfactant self-assembly, because they are both thermodynamically and electrostatically unfavorable in solution. It is evidently demonstrated that appropriately aqueous mixtures of single-tailed cationic and anionic (catanionic) surfactants can produce rigidly bacillus-shaped bilayer vesicles with both flat parts and bent edges. The crucial requirement for forming bacillus-shaped bilayer vesicles is the use of cationic surfactants with relatively hydrophobic [FeCl3Br]- as counterions. [FeCl3Br]- can strongly associate with cationic surfactants to partition into the hydrophobic bilayer of bacillus-shaped bilayer vesicles, significantly increasing the edge energy of cationic surfactants to make them distribute in the low curvature part of bilayers. This causes the formation of bacillus-shaped bilayer vesicles, but not completely bent spherical vesicles, in the case of cationic surfactant excess. The specificity of hydrophobic counterions, [FeCl3Br]-, could also make the catanionic mixtures do not precipitate at the stoichiometric point. This new self-assembly on catanionic systems is culminated in the discovery of beautifully structured colloidal objects which are of practical use for molecular templating and controlled drug or DNA release.


Asunto(s)
Compuestos de Cetrimonio/química , Compuestos Férricos/química , Membrana Dobles de Lípidos/química , Dodecil Sulfato de Sodio/química , Tensoactivos/química , Compuestos de Cetrimonio/síntesis química , Dispersión Dinámica de Luz , Compuestos Férricos/síntesis química , Interacciones Hidrofóbicas e Hidrofílicas , Fenómenos Magnéticos , Magnetometría , Difracción de Neutrones , Tamaño de la Partícula , Transición de Fase , Dispersión del Ángulo Pequeño , Electricidad Estática , Propiedades de Superficie , Tensoactivos/síntesis química
18.
Langmuir ; 32(33): 8366-73, 2016 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-27490998

RESUMEN

Precise control of phase structure transition for the synthesis of multi-dimensional soft materials is a fascinating target in amphiphilic molecule self-assembly. Here, we demonstrate a spontaneous formation of a closely packed lamellar phase consisting of uni- and multi-lamellar vesicles through the incorporation of a small amount of an extractant, di(2-ethylhexyl)phosphoric acid (DEHPA), into the highly swollen, planar lamellar phase of a non-ionic tetraethylene glycol monododecyl ether (C12EO4) surfactant in water. It is figured out that the introduction of negative membrane charges results in the electrostatic repulsion among the lamellae, which suppresses the Helfrich undulation and induces a phase structure transition from planar lamellae to closely packed vesicles. Our results provide important insight into amphiphilic molecule self-assembly, where additives and pH can satisfy the opportunities for the precise tuning of the lamellar structures, which makes a way for the development of lamellar soft materials.

19.
J Colloid Interface Sci ; 478: 303-10, 2016 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-27314643

RESUMEN

Colloidal chirality in wormlike micellar systems exclusively originated from achiral species and discussion of the role of secondary assembly of fiber-like aggregates in chirality generation were presented in this paper. Herein, formation of colloidal wormlike micelles for the first time incorporated chirality and redox-responsiveness into one design via noncovalent interaction. A dual-stimuli-responsive gel of wormlike micelles which were designed by employing a dual-responsive cationic surfactant (FTMA) and a strong gelator (AzoNa4) and regulated by redox reaction and host-guest inclusion is presented. Both the redox and host-guest interaction play an important role in regulating the viscosity and supramolecular chirality of gels of the wormlike micelles. The supramolecular chirality and viscosity of the wormlike micelle gels were switched reversibly by exerting chemical redox onto the ferrocenyl groups. For the amphiphile FTMA containing redox-active ferrocenyl group, reversible control of the oxidation state of ferrocenyl groups leads to the charge and hydrophobicity changes of FTMA, therefore change its self-assembly behavior. Of equal interest, ß-CD successfully detached the wormlike micelles via the recognition-inclusion behavior with FTMA and invalidate the H-bond and hydrophobic interaction between FTMA and AzoH4. This designed system provides a new strategy to tune the supramolecular chirality of colloidal aggregates and explore the specific packing mode detail within the micelles or the secondary assembly of the inter-micelles. We anticipate this dual-responsive H-bond-directed chiral gel switch could propose a new strategy when researchers designing new, multi-responsive functional gel materials.

20.
Chem Commun (Camb) ; 52(43): 6993-6, 2016 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-27156999

RESUMEN

Metal-organic gels (MOGs) of three-dimensional (3D) networks comprising nanosheets of ∼30 nm thickness and square-micrometer in size were easily produced via coordination interactions of iron (Fe(3+)) and 1,4-naphthalenedicarboxylic acid (NDC). Such MOGs exhibit ultrahigh removal of arsenic(v) in water, with the adsorption capacity of 144 mg g(-1), dramatically superior to those of the recently reported Fe-based inorganic and organic adsorbents.


Asunto(s)
Arsenicales/aislamiento & purificación , Quelantes/química , Compuestos Férricos/química , Estructuras Metalorgánicas/química , Naftalenos/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Módulo de Elasticidad , Concentración de Iones de Hidrógeno , Cinética , Estructuras Metalorgánicas/síntesis química , Modelos Químicos , Estructura Molecular , Nanoestructuras , Reología
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