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1.
Exp Dermatol ; 32(9): 1451-1458, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37309674

RESUMEN

Keratinocytes are the predominant cell type in the skin epidermis, and they not only protect the skin from the influence of external physical factors but also function as an immune barrier against microbial invasion. However, little is known regarding the immune defence mechanisms of keratinocytes against mycobacteria. Here, we performed single-cell RNA sequencing (scRNA-seq) on skin biopsy samples from patients with Mycobacterium marinum infection and bulk RNA sequencing (bRNA-seq) on M. marinum-infected keratinocytes in vitro. The combined analysis of scRNA-seq and bRNA-seq data revealed that several genes were upregulated in M. marinum-infected keratinocytes. Further in vitro validation of these genes by quantitative polymerase chain reaction and western blotting assay confirmed the induction of IL-32 in the immune response of keratinocytes to M. marinum infection. Immunohistochemistry also showed the high expression of IL-32 in patients' lesions. These findings suggest that IL-32 induction is a possible mechanism through which keratinocytes defend against M. marinum infection; this could provide new targets for the immunotherapy of chronic cutaneous mycobacterial infections.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium marinum , Humanos , Mycobacterium marinum/genética , Infecciones por Mycobacterium no Tuberculosas/genética , Infecciones por Mycobacterium no Tuberculosas/microbiología , Queratinocitos , Inmunidad
2.
Opt Lett ; 47(21): 5525-5528, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37219260

RESUMEN

Ti2AlC is a kind of ternary layered structured ceramic metal compound, combining the advantages of both ceramic and metal. Herein, the saturable absorption performance of Ti2AlC at the 1-µm wave band is investigated. The Ti2AlC behaves with excellent saturable absorption, which has a modulation depth of 14.53% and a saturable intensity of 13.27 MW/cm2. An all-normal dispersion fiber laser based on the Ti2AlC saturable absorber (SA) is constructed. The repetition frequency of the Q switched pulses increased from 44 to 49 kHz as the pump power rose from 276 to 365 mW, and the corresponding pulse width decreased from 3.64 to 2.42 µs. The maximum output single Q switched pulse energy is as high as 169.8 nJ. Our experiments prove that the MAX phase Ti2AlC has potential as a low-cost, simple preparation, and broadband SA material. To the best of our knowledge, this is the first demonstration of Ti2AlC serving as a SA material achieving Q switched operation at the 1-µm wave band.

3.
Lasers Med Sci ; 36(2): 387-399, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32557002

RESUMEN

Laser speckle contrast imaging (LSI) is a promising non-invasive full-field blood flow monitoring technique. However, it is still far from clinic practice due to insufficient contrast-to-noise ratio (CNR) and limited detection depth. In this study, an in vivo laser speckle imaging visualization system was constructed to observe the blood circulation on a dorsal skin. A dynamic laser speckle imaging (dLSI) scheme, other than traditional laser speckle contrast analysis method, was applied to separate the dynamic light scattering from the static one to increase the image CNR. Based on the theoretical optimization for dLSI, at least two pixels are required for speckle pattern sampling and a spatial window size of 7 × 7 was optimal to balance the spatial resolution and statistical accuracy. The in vivo experiment observation shows that the CNR is improved 8.4 times by dLSI. The blood vessels were more pronounced, and more capillaries can be observed than in traditional laser speckle contrast images. Topical optical clearing technique by thiazone was combined with dLSI to increase the sampling depth from 700 to 1000 µm.


Asunto(s)
Imágenes de Contraste de Punto Láser , Flujo Sanguíneo Regional , Algoritmos , Animales , Simulación por Computador , Femenino , Hemodinámica , Análisis Numérico Asistido por Computador , Imagen Óptica , Fantasmas de Imagen , Ratas Sprague-Dawley , Piel/irrigación sanguínea , Piel/diagnóstico por imagen , Factores de Tiempo
4.
Chem Biodivers ; 18(9): e2100460, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34369658

RESUMEN

A new compound named koninginin W (1) and four known polyketides (2-5) were isolated from endophytic fungus Trichoderma koningiopsis YIM PH30002 of Panax notoginseng. The structures of 1 - 5, including absolute configuration of 1, were elucidated on the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, and X-ray crystallographic data. Koninginin W (1) presented weak antibacterial activity against Escherichia coli, Bacillus subtilis and Salmonella typhimurium.


Asunto(s)
Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Trichoderma/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Conformación Molecular
5.
Indian J Microbiol ; 61(4): 519-523, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34744207

RESUMEN

Ten compounds (1-10) were obtained from soil-derived Penicillium cremeogriseum W1-1 with the antimicrobial guided isolation procedure. Among them, 4 presented broad-spectrum antimicrobial activities and its preliminary mechanisms were evaluated. Compound 4 showed growth inhibition on drug-resistant pathogenic strains Escherichia coli and Candida albicans with post-contact effect (PCE), changed the morphology and membrane structure, killed cells with leakage, inhibited the growth of C. albicans by eradicating biofilms. Interestingly, the fraction containing 4 presented in vivo anti-pathogenic activities in mice, indicating this indole diterpenoid alkaloid could been used as potential antimicrobial agent.

6.
Opt Express ; 27(20): 27726-27736, 2019 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-31684535

RESUMEN

The Au@SiO2 nanorods with two plasmonic resonance bands are used to enhance and tune the emission of binary lanthanide (Eu/Tb) complexes. The emissions of Tb and Eu ions are both enhanced, the maximum enhancement is over 100-fold. Meanwhile the ratio and relative intensity of the red/green bands is altered by the strong coupling between complexes and nanorods, tuning the color of emission from green to yellow under excitation of 292 nm and improving the color purity from orange to red under excitation of 360 nm. The underlying physics of the lanthanide complex-plasmonic nanorod composite system is analyzed, which deepen the understanding of the interaction between complexes and plasmon nanoparticles.

7.
Zhong Yao Cai ; 38(11): 2394-8, 2015 Nov.
Artículo en Zh | MEDLINE | ID: mdl-27356393

RESUMEN

OBJECTIVE: To establish an HPLC method for characteristic chromatograms analysis and simultaneous determination of six marker components in Xinnaojian Capsules from different manufactories. METHODS: Using HPLC, an Agilent C18 column (100 mm x 4.6 mm, 2.7 µm) was adopted with acetonitrile-0.05% phosphoric acid as the mobile phase in a gradient elution mode, the flow ratewas 0.4 mL/min, the detection wavelength was 280 nm, and the column temperature was 40 degrees C. RESULTS: Totally eleven common peaks were recognized with epigallocatechin-3-gallate as the reference peak. There were good similarities between the standard characteristic chromatogram and each characteristic chromatogram of the 26 samples with their similarities over 0.99. The six marker components (gallic acid, gallocatechin, caffeine, epigallocatechin, epigallocatechin-3-gallate and epicatechin gallate) were separated well. Good correlation coefficients were found (r > 0.9990) and the average recovery rates ranged from 95.29% to 102.3%. CONCLUSION: The established method has high sensitivity and specificity, and can be used for the quality control of Xinnaojian Capsules.


Asunto(s)
Medicamentos Herbarios Chinos/química , Control de Calidad , Cafeína/análisis , Cápsulas , Catequina/análogos & derivados , Catequina/análisis , Cromatografía Líquida de Alta Presión , Ácido Gálico/análisis
8.
ACS Appl Mater Interfaces ; 16(2): 2888-2901, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38165225

RESUMEN

Physically unclonable function (PUF) methods have high security, but their wide application is limited by complex encoding, large database, advanced external characterization equipment, and complicated comparative authentication. Therefore, we creatively propose the physically unclonable holographic encryption and anticounterfeiting based on the light propagation of complex medium and fluorescent labels. As far as we know, this is the first holographic encryption and anticounterfeiting method with a fluorescence physically unclonable property. The proposed method reduces the above requirements of traditional PUF methods and significantly reduces the cost. The angle-multiplexed PUF fluorescent label is the physical secret key. The information is encrypted as computer-generated holograms (CGH). Many physical parameters in the system are used as the parameter secret keys. The Diffie-Hellman key exchange algorithm is improved to transfer parameter secret keys. A variety of complex medium hologram generation methods are proposed and compared. The effectiveness, security, and robustness of the method are studied and analyzed. Finally, a graphical user interface (GUI) is designed for the convenience of users. The advantages of this method include lower PUF encoding complexity, effective reduction of the database size, lower requirements for characterization equipment, and direct use of decrypted information without complicated comparative authentication to reduce misjudgment. It is believed that the method proposed in this paper will pave the way for the popularization and application of PUF-based anticounterfeiting and encryption methods.

9.
ACS Appl Mater Interfaces ; 15(19): 23527-23537, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37140148

RESUMEN

In photopolymerization-induced 3D printing of glass and ceramics, the demand for a slurry that has high photosensitivity, low viscosity, and high solid content leads to a limited selection of suspended particles. To this end, ultraviolet-assisted direct ink writing (UV-DIW) is proposed as a new 3D printing compatible approach. A curable UV ink is synthesized, which overcomes the material limitation. Benefiting from the advantage of the UV-DIW process, CaAlSiN3:Eu2+/BaMgAl10O17:Eu2+ phosphors in glass (CASN/BAM-PiG) as chromaticity-tunable specially shaped all-inorganic color converters are prepared for plant growth lighting using an optimized heat treatment procedure. Size compatible dome-type and flat-type CaAlSiN3:Eu2+ phosphors in glass (CASN-PiG) are constructed in batches. The manufactured dome-type PiG-based light-emitting diodes (LEDs) exhibit better heat dissipation capacity and a larger divergence angle. The advantage of CASN/BAM-PiG in plant growth lighting is confirmed by the high degree of resemblance between the emission spectra of CASN/BAM-PiG and the absorption spectra of carotenoid and chlorophyll. A series of dome-type CASN/BAM-PiG based LEDs with selective region doping are constructed, which can weaken reabsorption effects and scientifically match the requirements of different plants. The excellent color-tunable ability and high degree of spectral resemblance indicate the superiority of the proposed UV-DIW process in all-inorganic CASN/BAM-PiG color converters for intelligent agricultural lighting.

10.
Nanoscale ; 15(23): 10141-10148, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37265388

RESUMEN

Polarized luminescence has many applications in energy saving, displays, communication and other fields. Here, electrically tunable polarized luminescence of aligned Eu(tta)3phen/E7 composites is successfully obtained based on the interaction between liquid crystal (LC) hosts and rare earth (RE) complex guests. The generation mechanism of the polarization effect is thoroughly explored from three different aspects. The polarized luminescence of Eu(tta)3phen/E7 composites is closely related to the polarized energy absorption of incident light, the site symmetry of Eu3+ ions for oriented Eu(tta)3phen complex molecules, and the polarized energy transfer from E7 to Eu(tta)3phen. The convenient control of the well-aligned Eu(tta)3phen complex by simply embedding the Eu(III) complex guest in the E7 host and utilizing small-magnitude electric field forces is explicitly confirmed. The E7 host not only provides the orientation condition for the electrically tunable polarized luminescence but also promotes the degree of polarization through polarized energy transfer. The polarized spectral properties and the symmetry of the Eu3+ site of the aligned Eu(tta)3phen complexes are described in detail. The analysis of the generation mechanism of polarized luminescence supplements the research content in the field of RE/LC composites and paves the way for exciting novel advances in the field of polarized emission.


Asunto(s)
Cristales Líquidos , Metales de Tierras Raras , Luminiscencia , Metales de Tierras Raras/química , Electricidad , Transferencia de Energía
11.
J Immunol Res ; 2023: 3804605, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37767202

RESUMEN

Background: Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identity and the pathogenesis of multiple cancers. Belonging to the cytosolute linker protein group, FYB1 is essential for TCR signaling and extensively studied in terms of tumor pathogenesis and metastasis. Dissecting the role of FYN binding protein 1 (FYB1) in T-ALL holds the potential to improve the treatment outcome and prognosis of T-ALL. Methods: In this study, SEs were explored using public H3K27ac ChIP-seq data derived from T-ALL cell lines, AML cell lines and hematopoietic stem and progenitor cells (HSPCs). Downstream target of FYB1 gene was identified by RNA-seq. Effects of shRNA-mediated downregulation of FYB1 and immunoglobulin lambda-like polypeptide 1 (IGLL1) on self-renewal of T-ALL cells were evaluated in vitro and/or in vivo. Results: As an SE-driven gene, overexpression of FYB1 was observed in T-ALL, according to the Cancer Cell Line Encyclopedia database. In vitro, knocking down FYB1 led to comprised growth and enhanced apoptosis of T-ALL cells. In vivo, downregulation of FYB1 significantly decreased the disease burden by suppressing tumor growth and improved survival rate. Knocking down FYB1 resulted in significantly decreased expression of IGLL1 that was also an SE-driven gene in T-ALL. As a downstream target of FYB1, IGLL1 exerted similar role as FYB1 in inhibiting growth of T-ALL cells. Conclusion: Our results suggested that FYB1 gene played important role in regulating self-renewal of T-ALL cells by activating IGLL1, representing a promising therapeutic target for T-ALL patients.

12.
Hematology ; 28(1): 2247253, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37594294

RESUMEN

INTRODUCTION: B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While the majority of B-ALL patients (90%) experience successful recovery, early relapse cases of B-ALL continue to exhibit high mortality rates. MZ1, a novel inhibitor of Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective of this study was to examine the role and therapeutic potential of MZ1 in the treatment of B-ALL. METHODS: In order to ascertain the fundamental mechanism of MZ1, a sequence of in vitro assays was conducted on B-ALL cell lines, encompassing Cell Counting Kit 8 (CCK8) assay, Propidium iodide (PI) staining, and Annexin V/PI staining. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to examine protein and mRNA expression levels. Transcriptomic RNA sequencing (RNA-seq) was utilized to screen the target genes of MZ1, and lentiviral transfection was employed to establish stably-expressing/knockdown cell lines. RESULTS: MZ1 has been observed to induce the degradation of Bromodomain Containing 4 (BRD4), Bromodomain Containing 3 (BRD3), and Bromodomain Containing 2 (BRD2) in B-ALL cell strains, leading to inhibited cell growth and induction of cell apoptosis and cycle arrest in vitro. These findings suggest that MZ1 exhibits cytotoxic effects on two distinct molecular subtypes of B-ALL, namely 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines. Additionally, RNA-sequencing analysis revealed that MZ1 significantly downregulated the expression of Cyclin D3 (CCND3) gene in B-ALL cell lines, which in turn promoted cell apoptosis, blocked cell cycle, and caused cell proliferation inhibition. CONCLUSION: Our results suggest that MZ1 has potential anti-B-ALL effects and might be a novel therapeutic target.


Asunto(s)
Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Proteínas de Ciclo Celular/genética , Ciclina D3 , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Factores de Transcripción/genética
13.
Cell Death Dis ; 14(8): 518, 2023 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-37573405

RESUMEN

One of the characteristics of leukemia is that it contains multiple rearrangements of signal transduction genes and overexpression of non-mutant genes, such as transcription factors. As an important regulator of hematopoietic stem cell development and erythropoiesis, LMO2 is considered an effective carcinogenic driver in T cell lines and a marker of poor prognosis in patients with AML with normal karyotype. LDB1 is a key factor in the transformation of thymocytes into T-ALL induced by LMO2, and enhances the stability of carcinogenic related proteins in leukemia. However, the function and mechanism of LMO2 and LDB1 in AML remains unclear. Herein, the LMO2 gene was knocked down to observe its effects on proliferation, survival, and colony formation of NB4, Kasumi-1 and K562 cell lines. Using mass spectrometry and IP experiments, our results showed the presence of LMO2/LDB1 protein complex in AML cell lines, which is consistent with previous studies. Furthermore, in vitro and in vivo experiments revealed that LDB1 is essential for the proliferation and survival of AML cell lines. Analysis of RNA-seq and ChIP-Seq results showed that LDB1 could regulate apoptosis-related genes, including LMO2. In LDB1-deficient AML cell lines, the overexpression of LMO2 partially compensates for the proliferation inhibition. In summary, our findings revealed that LDB1 played an important role in AML as an oncogene, and emphasize the potential importance of the LMO2/LDB1 complex in clinical treatment of patients with AML.


Asunto(s)
Proteínas de Unión al ADN , Leucemia Mieloide Aguda , Humanos , Proteínas de Unión al ADN/metabolismo , Proteínas con Homeodominio LIM/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Eritropoyesis , Leucemia Mieloide Aguda/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo
14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(1): 80-84, 2022 Jan.
Artículo en Zh | MEDLINE | ID: mdl-35307066

RESUMEN

OBJECTIVE: To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS). METHODS: A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. RESULTS: A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO2/FiO2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO2/FiO2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO2/FiO2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found (P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. CONCLUSIONS: Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO2/FiO2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.


Asunto(s)
Surfactantes Pulmonares , Síndrome de Dificultad Respiratoria del Recién Nacido , Administración por Inhalación , Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Humanos , Recién Nacido , Recien Nacido Prematuro , Nebulizadores y Vaporizadores , Estudios Prospectivos , Surfactantes Pulmonares/administración & dosificación , Surfactantes Pulmonares/efectos adversos , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico
15.
Cancer Biol Ther ; 23(1): 1-15, 2022 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-36170346

RESUMEN

Acute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance and relapse resulting in high mortality. Recently, bromodomains and extra-terminal (BET) protein inhibitors have been extensively researched in hematological tumors as potential anticancer agents. MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML. In this study, we first identified that AML patients with high BRD4 expression had poor overall survival than those with low expression group. MZ1 inhibited AML cell growth and induced apoptosis and cycle arrest in vitro. MZ1 induced degradation of BRD4, BRD3 and BRD2 in AML cell strains. Additionally, MZ1 also initiated the cleavage of poly-ADP-ribose polymerase (PARP), which showed cytotoxic effects on NB4 (PML-RARa), K562 (BCR-ABL), Kasumi-1 (AML1-ETO), and MV4-11 (MLL-AF4) cell lines representing different molecular subtypes of AML. In AML mouse leukemia model, MZ1 significantly decreased leukemia cell growth and increased the mouse survival time. According to the RNA-sequencing analysis, MZ1 led to c-Myc and ANP32B genes significant downregulation in AML cell lines. Knockdown of ANP32B promoted AML cell apoptosis and inhibited cell growth. Overall, our data indicated that MZ1 had broad anti-cancer effects on AML cell lines with different molecular lesions, which might be exploited as a novel therapeutic strategy for AML patients.


Asunto(s)
Antineoplásicos , Dipéptidos , Compuestos Heterocíclicos con 3 Anillos , Leucemia Mieloide Aguda , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Dipéptidos/farmacología , Compuestos Heterocíclicos con 3 Anillos/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Proteolisis , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN , Factores de Transcripción/metabolismo
16.
J Immunol Res ; 2022: 7912484, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958877

RESUMEN

Background: AML (acute myeloid leukemia) is a common hematological malignancy in children with poor treatment effects and poor prognosis. Recent studies have shown that as a novel BRD4 (bromodomain containing 4) PROTACs (proteolysis targeting chimeras) degrader, GNE-987 can slow down the growth of various tumors and increase apoptosis, with promising clinical prospects. However, the function and molecular mechanism of GNE-987 in AML remain unclear. This study is aimed at investigating the therapeutic effect of GNE-987 on AML and its underlying mechanism. Methods: The association between BRD4 and AML was assessed by studying public databases. After GNE-987 was added to AML cells, cell proliferation slowed down, the cycle was disturbed, and apoptosis increased. Western blotting was used to detect BRD2 (bromodomain containing 2), BRD3 (bromodomain containing 3), BRD4, and PARP (poly ADP-ribose polymerase) proteins. The effect of GNE-987 on AML cells was analyzed in vivo. RNA-seq (RNA sequencing) and ChIP-seq (chromatin immunoprecipitation sequencing) validated the function and molecular pathways of GNE-987 in processing AML. Results: BRD4 expression was significantly elevated in pediatric AML samples compared with healthy donors. GNE-987 inhibited AML cell proliferation by inhibiting the cell cycle and inducing apoptosis. BRD2, BRD3, and BRD4 were consistent with decreased VHL (Von Hippel Lindau) expression in AML cells. In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time. Based on analysis of RNA-seq and ChIP-seq analyses, GNE-987 could target multiple SE- (super-enhancer-) related genes, including LYL1 (lymphoblastic leukemia 1), to inhibit AML. Conclusions: GNE-987 had strong antitumor activity in AML. GNE-987 could effectively inhibit the expression of SE-related oncogenes including LYL1 in AML. Our results suggested that GNE-987 had broad prospects in the treatment of AML.


Asunto(s)
Leucemia Mieloide Aguda , Proteínas Nucleares , Animales , Apoptosis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Ratones , Proteínas de Neoplasias , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
17.
Pathol Oncol Res ; 28: 1610447, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35832114

RESUMEN

Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities to achieve better treatment outcomes. However, due to the complex heterogeneity of AML, its prognosis remains dismal. In this study, we first identified the correlation between high expression of BRD4 and overall survival of patients with AML. Targeted degradation of BRD2, BRD3, and BRD4 proteins by dBET1, a proteolysis-targeting chimera (PROTAC) against the bromodomain and extra-terminal domain (BET) family members, showed cytotoxic effects on Kasumi (AML1-ETO), NB4 (PML-RARa), THP-1 (MLL-AF9), and MV4-11 (MLL-AF4) AML cell lines representing different molecular subtypes of AML. Furthermore, we determined that dBET1 treatment arrested cell cycling and enhanced apoptosis and c-MYC was identified as the downstream target. Collectively, our results indicated that dBET1 had broad anti-cancer effects on AML cell lines with different molecular lesions and provided more benefits to patients with AML.


Asunto(s)
Leucemia Mieloide Aguda , Proteínas Nucleares , Humanos , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Péptidos y Proteínas de Señalización Intercelular , Leucemia Mieloide Aguda/patología , Proteínas Nucleares/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-myc , Factores de Transcripción/metabolismo
18.
J Exp Clin Cancer Res ; 41(1): 225, 2022 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-35842703

RESUMEN

BACKGROUND: Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis. METHODS: ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. RESULTS: We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells. CONCLUSIONS: In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Leucemia Mieloide Aguda , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Ciclo Celular , Niño , Humanos , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética
19.
Nanomaterials (Basel) ; 11(4)2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33921613

RESUMEN

Lanthanide materials have great applications in optical communication, biological fluorescence imaging, laser, and so on, due to their narrow emission bandwidths, large Stokes' shifts, long emission lifetimes, and excellent photo-stability. However, the photon absorption cross-section of lanthanide ions is generally small, and the luminescence efficiency is relatively low. The effective improvement of the lanthanide-doped materials has been a challenge in the implementation of many applications. The local surface plasmon resonance (LSPR) effect of plasmonic nanoparticles (NPs) can improve the luminescence in different aspects: excitation enhancement induced by enhanced local field, emission enhancement induced by increased radiative decay, and quenching induced by increased non-radiative decay. In addition, plasmonic NPs can also regulate the energy transfer between two close lanthanide ions. In this review, the properties of the nanocomposite systems of lanthanide material and plasmonic NPs are presented, respectively. The mechanism of lanthanide materials regulated by plasmonic NPs and the scientific and technological discoveries of the luminescence technology are elaborated. Due to the large gap between the reported enhancement and the theoretical enhancement, some new strategies applied in lanthanide materials and related development in the plasmonic enhancing luminescence are presented.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 261: 120002, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34090095

RESUMEN

The utilization and residue of pesticides exist multifaceted non-restrictive effects on food safety and ecological protection. Exploitation of rapid and sensitive pesticide detection technology is imperative and will be helpful to better control the detriment of pesticides. Here, a novel flexible film has been prepared based on organic-inorganic composite materials (coumarin-3-carboxylic acid and GdF3:Sm3+), which exhibits good optical performance and can well realize the timely and maneuverable detection for different pesticides. The spectra and luminescence properties of each composition in the composite have been analyzed systematically, and the coordinated fluorescence emission of Sm3+ and coumarin-3-carboxylic acid is revealed at an excitation wavelength of 373 nm. Besides, the energy transfer mechanism is also researched by both experiment and theoretical calculation. The actual detection of different pesticides reveals differential fluorescence influence degree. Meanwhile, the flexible film still possesses sensitive recognition in the presence of micro concentration of pesticides. Results indicate that the flexible film with good optical performance can produce visual detection ability and provide a promising strategy for wider detection applications.


Asunto(s)
Plaguicidas , Cumarinas , Luminiscencia , Plaguicidas/análisis , Espectrometría de Fluorescencia
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