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1.
J Am Chem Soc ; 144(42): 19382-19395, 2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36251010

RESUMEN

Many of the highest-performing polymer photocatalysts for sacrificial hydrogen evolution from water have contained dibenzo[b,d]thiophene sulfone units in their polymer backbones. However, the reasons behind the dominance of this building block are not well understood. We study films, dispersions, and solutions of a new set of solution-processable materials, where the sulfone content is systematically controlled, to understand how the sulfone unit affects the three key processes involved in photocatalytic hydrogen generation in this system: light absorption; transfer of the photogenerated hole to the hole scavenger triethylamine (TEA); and transfer of the photogenerated electron to the palladium metal co-catalyst that remains in the polymer from synthesis. Transient absorption spectroscopy and electrochemical measurements, combined with molecular dynamics and density functional theory simulations, show that the sulfone unit has two primary effects. On the picosecond timescale, it dictates the thermodynamics of hole transfer out of the polymer. The sulfone unit attracts water molecules such that the average permittivity experienced by the solvated polymer is increased. We show that TEA oxidation is only thermodynamically favorable above a certain permittivity threshold. On the microsecond timescale, we present experimental evidence that the sulfone unit acts as the electron transfer site out of the polymer, with the kinetics of electron extraction to palladium dictated by the ratio of photogenerated electrons to the number of sulfone units. For the highest-performing, sulfone-rich material, hydrogen evolution seems to be limited by the photogeneration rate of electrons rather than their extraction from the polymer.

2.
Exp Cell Res ; 409(2): 112909, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34742742

RESUMEN

LncRNA contribution to self-renewal of bladder cancer stem-like cells (CSLCs) remains largely unknown. We investigated the expression profile and biological function of lncRNAs in urothelial CSLCs by microarray analysis. Among these, lncRNA-AK023096 was identified as potentially playing a role in maintaining self-renewal of CSLCs. Knockdown of this transcript inhibited spheroid formation and tumor formation. We found that AK023096 mediates recruitment of hnRNP-K to SOX2 promoter and increases H3K4 trimethylation status on SOX2 promoter, leading to a robust change in SOX2 mRNA and protein levels. Moreover, AK023096 expression in primary tumors was found to be a powerful predictor of recurrence following transurethral resection in patients with nonmuscle-invasive bladder cancer, highlighting the critical role of lncRNA in the bladder cancer regulatory network.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Autorrenovación de las Células , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Células Madre Neoplásicas/patología , ARN Largo no Codificante/genética , Factores de Transcripción SOXB1/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Animales , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/metabolismo , Pronóstico , Regiones Promotoras Genéticas , Factores de Transcripción SOXB1/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
3.
J Cell Mol Med ; 25(5): 2563-2571, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33523599

RESUMEN

Lung cancer is one of the major cause for high-death rate all over the world, due to increased metastasize and difficulties in diagnosis. Naringenin is naturally occurring flavonoid found in various fruits including tomatoes, citrus fruit and figs. Naringenin is known to have several therapeutic effects including anti-atherogenic, antimicrobial, anti-inflammatory, hepatoprotective, anticancer and anti-mutagenic. The present study was aimed to analyse the naringenin induced anti-proliferative and apoptosis effects in human lung cancer cells. Cells were treated with various concentrations of naringenin (10, 100 & 200 µmol/L) for 48 hours. Cisplatin (20 µg/mL) was used as positive control. Cell viability, apoptosis, migration and mRNA, and protein expression of caspase-3, matrixmetallo proteinases-2 (MMP-2) and MMP-9 were determined. The cell viability was 93.7 ± 7.5, 51.4 ± 4.4 and 32.1 ± 2.1 at 10, 100 and 200 µmol/L of naringenin respectively. Naringenin significantly increased apoptotic cells. The 100 and 200 µmol/L of naringenin significantly suppressed the larger wounds of cultured human cancer cells compared with the untreated lung cancer cells. Naringenin increased d the expression of caspase-3 and reduced the expression of MMP-2 and MMP-9. Taking all these data together, it is suggested that the naringenin was effective against human lung cancer proliferation, migration and metastasis.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Movimiento Celular/inmunología , Flavanonas/farmacología , Animales , Biomarcadores , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Humanos , Ratones
4.
J Biochem Mol Toxicol ; 33(6): e22319, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30897277

RESUMEN

Oxidative stress is performing an essential role in developing Alzheimer's disease (AD), and age-related disorder and other neurodegenerative diseases. In existing research, we have aimed at investigating the daidzein (4',7-dihydroxyisoflavone) effect (10 and 20 mg/kg of body weight), as a free radical scavenger and antioxidant in streptozotocin (STZ) infused AD in rat model. Daidzein treatment led to significant improvement in intracerebroventricular-streptozotocin (ICV-STZ)-induced memory and learning impairments that was evaluated by Morris water maze test and spontaneous locomotor activity. It significantly restored the alterations in malondialdehyde, catalase, superoxide dismutase, and reduced glutathione levels. In addition, histopathological observations in cerebral cortex and hippocampal areas confirmed the neuroprotective effect of daidzein. These outcomes provide experimental proof showing preventive effect of daidzein on memory, learning dysfunction and oxidative stress in case of ICV-STZ rats. In conclusion, daidzein offers a potential treatment module for various neurodegenerative disorders with regard to mental deficits like AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Isoflavonas/farmacología , Estrés Oxidativo/efectos de los fármacos , Estreptozocina/toxicidad , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/prevención & control , Animales , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/prevención & control , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Wistar
5.
Database (Oxford) ; 20242024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38917209

RESUMEN

Major depressive disorder (MDD) is a pressing global health issue. Its pathogenesis remains elusive, but numerous studies have revealed its intricate associations with various biological factors. Consequently, there is an urgent need for a comprehensive multi-omics resource to help researchers in conducting multi-omics data analysis for MDD. To address this issue, we constructed the MDDOmics database (Major Depressive Disorder Omics, (https://www.csuligroup.com/MDDOmics/), which integrates an extensive collection of published multi-omics data related to MDD. The database contains 41 222 entries of MDD research results and several original datasets, including Single Nucleotide Polymorphisms, genes, non-coding RNAs, DNA methylations, metabolites and proteins, and offers various interfaces for searching and visualization. We also provide extensive downstream analyses of the collected MDD data, including differential analysis, enrichment analysis and disease-gene prediction. Moreover, the database also incorporates multi-omics data for bipolar disorder, schizophrenia and anxiety disorder, due to the challenge in differentiating MDD from similar psychiatric disorders. In conclusion, by leveraging the rich content and online interfaces from MDDOmics, researchers can conduct more comprehensive analyses of MDD and its similar disorders from various perspectives, thereby gaining a deeper understanding of potential MDD biomarkers and intricate disease pathogenesis. Database URL: https://www.csuligroup.com/MDDOmics/.


Asunto(s)
Bases de Datos Genéticas , Trastorno Depresivo Mayor , Trastorno Depresivo Mayor/genética , Humanos , Polimorfismo de Nucleótido Simple , Genómica/métodos , Metilación de ADN/genética , Multiómica
6.
Biomol Biomed ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38552230

RESUMEN

Radiation-induced lung injury (RILI) frequently occurs as a complication following radiotherapy for chest tumors like lung and breast cancers. However, the precise underlying mechanisms of RILI remain unclear. In this study, we generated RILI models in rats treated with a single dose of 20 Gy and examined lung tissues by single-cell RNA sequencing (scRNA-seq) 2 weeks post-radiation. Analysis of lung tissues revealed 18 major cell populations, indicating an increase in cell-cell communication following radiation exposure. Neutrophils, macrophages, and monocytes displayed distinct subpopulations and uncovered potential for pro-inflammatory effects. Additionally, endothelial cells exhibited a highly inflammatory profile and the potential for reactive oxygen species (ROS) production. Furthermore, smooth muscle cells (SMC) showed a high propensity for extracellular matrix (ECM) deposition. Our findings broaden the current understanding of RILI and highlight potential avenues for further investigation and clinical applications.

7.
Nanoscale ; 16(24): 11623-11632, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38864422

RESUMEN

Circular dichroism spectroscopy is a key probe of the structural and optical properties of chiral materials, however, commercial circular dichroism spectrometers are large, prohibitively expensive and rarely offer environmental control of the sample under test. Using Fresnel rhombs as inexpensive broadband quarter-wave plates, we demonstrate two novel, low-cost (<£2000) and portable imaging systems controlled by our own bespoke open-source control software which are capable of spatially mapping the circular dichroism of chiral solid state films. By coupling these imaging systems with a temperature controlled stage, we show that we can rapidly identify the thermal processing conditions required to maximise circular dichroism in chiral solid state films by measuring circular dichroism in situ during thermal annealing of a sample under test. The accuracy and spatial resolution of these circular dichroism imagers are cross-compared against our previous studies using an existing circular dichroism imaging system at the Diamond Light Source and are shown to be in good agreement, with a sensitivity down to 250 mdeg and a spatial resolution of 100 µm.

8.
Acta Pharm Sin B ; 14(2): 698-711, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38322340

RESUMEN

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with ß-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of ß-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher ß-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing ß-Catenin to inhibit the progress of gastric cancer.

9.
Chem Mater ; 36(1): 425-438, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38222935

RESUMEN

Higher adducts of a fullerene, such as the bis-adduct of PCBM (bis-PCBM), can be used to achieve shallower molecular orbital energy levels than, for example, PCBM or C60. Substituting the bis-adduct for the parent fullerene is useful to increase the open-circuit voltage of organic solar cells or achieve better energy alignment as electron transport layers in, for example, perovskite solar cells. However, bis-PCBM is usually synthesized as a mixture of structural isomers, which can lead to both energetic and morphological disorder, negatively affecting device performance. Here, we present a comprehensive study on the molecular properties of 19 pure bis-isomers of PCBM using a variety of characterization methods, including ultraviolet photoelectron spectroscopy, thermal gravimetric analysis, differential scanning calorimetry, single crystal structure, and (time-dependent) density functional theory calculation. We find that the lowest unoccupied molecular orbital of such bis-isomers can be tuned to be up to 170 meV shallower than PCBM and up to 100 meV shallower than the mixture of unseparated isomers. The isolated bis-isomers also show an electron mobility in organic field-effect transistors of up to 4.5 × 10-2 cm2/(V s), which is an order of magnitude higher than that of the mixture of bis-isomers. These properties enable the fabrication of the highest performing bis-PCBM organic solar cell to date, with the best device showing a power conversion efficiency of 7.2%. Interestingly, we find that the crystallinity of bis-isomers correlates negatively with electron mobility and organic solar cell device performance, which we relate to their molecular symmetry, with a lower symmetry leading to more amorphous bis-isomers, less energetic disorder, and higher dimensional electron transport. This work demonstrates the potential of side chain engineering for optimizing the performance of fullerene-based organic electronic devices.

10.
Acta Pharm Sin B ; 13(10): 4217-4233, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37799381

RESUMEN

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

11.
Oncogene ; 42(14): 1101-1116, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36792757

RESUMEN

Although N4-acetylcytidine (ac4C) modification affects the stability and translation of mRNA, it is unknown whether it exists in noncoding RNAs, and its biological function is unclear. Here, nucleotide-resolution method for profiling CTC-490G23.2 ac4C sites and gain- and loss-of-function experiments revealed that N-acetyltransferase 10 (NAT10) is responsible for ac4C modification of long noncoding RNAs (lncRNAs). NAT10-mediated ac4C modification leads to the stabilization and overexpression of lncRNA CTC-490G23.2 in primary esophageal squamous cell carcinoma (ESCC) and its further upregulation in metastatic tissues. CTC-490G23.2 significantly promotes cancer invasion and metastasis in vitro and in vivo. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the binding of CD44 pre-mRNA to polypyrimidine tract-binding protein 1 (PTBP1), resulting in a oncogenic splicing switch from the standard isoform CD44s to the variant isoform CD44v(8-10). CD44v(8-10), but not CD44s, binds to and increases the protein stability of vimentin. Expression levels of CTC-490G23.2 and CD44v(8-10) can predict poor prognosis in cancer patients. Furthermore, the antisense oligonucleotide (ASO)/SV40-LAH4-L1 peptide self-assembled nanocomplexes targeting CTC490G23.2 exerts a significantly suppressive effect on cancer metastasis. The outcome of this study will provide new mechanistic insight into the ac4C modification of lncRNAs and useful clues for the development of novel systemic therapies and prognostic biomarkers.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Empalme Alternativo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Isoformas de Proteínas/genética , Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo
12.
Cell Discov ; 9(1): 74, 2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37460462

RESUMEN

Posttranslational modification dramatically enhances protein complexity, but the function and precise mechanism of novel lysine acylation modifications remain unknown. Chemoresistance remains a daunting challenge to successful treatment. We found that lysine butyrylation (Kbu) is specifically upregulated in chemoresistant tumor cells and tissues. By integrating butyrylome profiling and gain/loss-of-function experiments, lysine 754 in HSP90 (HSP90 K754) was identified as a substrate for Kbu. Kbu modification leads to overexpression of HSP90 in esophageal squamous cell carcinoma (ESCC) and its further increase in relapse samples. Upregulation of HSP90 contributes to 5-FU resistance and can predict poor prognosis in cancer patients. Mechanistically, HSP90 K754 is regulated by the cooperation of KAT8 and HDAC11 as the writer and eraser, respectively; SDCBP increases the Kbu level and stability of HSP90 by binding competitively to HDAC11. Furthermore, SDCBP blockade with the lead compound V020-9974 can target HSP90 K754 to overcome 5-FU resistance, constituting a potential therapeutic strategy.

13.
J Transl Med ; 10: 110, 2012 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-22647238

RESUMEN

BACKGROUND: Increased expression of transcriptional coactivator p300 has been observed in a variety of human cancers. However, the expression status of p300 protein/mRNA in nasopharyngeal carcinoma (NPC) tissues and its clinicopathologic/prognostic implication are poorly understood. METHODS: In our study, mRNA and protein expression levels of p300 was explored by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC) in nasopharyngeal mucosal and NPC tissues. The data were analyzed by receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model. RESULTS: Up-regulated expression of p300 mRNA/p300 protein was detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal tissues. Based on ROC curve analysis, the cutoff score for p300 high expression was defined when more than 35% of the tumor cells were positively stained. High expression of p300 was observed in 127/209 (60.7%) of NPCs. In NPCs, high expression of p300 was positively associated with later T classification, later N classification, distant metastasis and later clinical stage (P < 0.05). In univariate survival analysis, overexpression of p300 was found to be an indicator of progression-free (P = 0.002) and overall survival (P = 0.001) in NPCs. More importantly, p300 expression was evaluated as an independent prognostic factor for NPC in multivariate analysis (P = 0.036). CONCLUSIONS: Our findings support that high expression of p300 protein might be important in conferring a more aggressive behavior, and is an independent molecular marker for shortened survival time of patients with NPC.


Asunto(s)
Neoplasias Nasofaríngeas/metabolismo , Factores de Transcripción p300-CBP/metabolismo , Western Blotting , Carcinoma , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/enzimología , Neoplasias Nasofaríngeas/patología , Pronóstico , Curva ROC , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Supervivencia
14.
Bioengineered ; 13(4): 10165-10176, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35435136

RESUMEN

To discuss the effect and molecular mechanism of circular RNA circ_0067741 on the occurrence and development of lung adenocarcinoma (LUAD). QRT-PCR was utilized to detect circ_0067741, microRNA-183-5p (miR-183-5p) and large tumor suppressor 1 (LATS1) expressions in tumor tissues of 30 LUAD patients and LUAD cell lines (A549, Calu-3, H1299 and H1975). After overexpression or knockdown of circ_0067741-1 or miR-183-5p in H1299 and A549 cells, respectively, cell proliferation, viability, apoptosis, invasion and migration ability and angiogenesis ability were detected by MTT, cell cloning, flow cytometry, transwell and tube formation assays, respectively. The targeted relationship between miR-183-5p and circ_0067741 or LATS1 was validated using dual-luciferase reporter assay. We found that circ_0067741 expression was notably declined in LUAD cells and tissues. Overexpression of circ_0067741 inhibited the proliferation, migration, invasion, and angiogenesis of LUAD cells and promoted apoptosis. Moreover, circ_0067741 could sponge miR-183-5p to regulate LATS1 expression and then activate the Hippo/YAP pathway. Downregulation of LATS1 reversed the effects of circ_0067741 on the Hippo/YAP pathway and LUAD cells progression. In conclusion, circ_0067741 sponges miR-183-5p, and regulates LATS1 to activate Hippo/YAP pathway, thereby inhibiting the process of LUAD cells. And the circ_0067741/miR-183-5p/LATS1 axis can be a potential target for early diagnosis and targeted treatment of LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , MicroARNs , Adenocarcinoma del Pulmón/metabolismo , Proliferación Celular/genética , Humanos , Neoplasias Pulmonares/patología , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/genética , ARN Circular/genética
15.
Cell Cycle ; 21(3): 304-321, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35007184

RESUMEN

Non-small cell lung cancer (NSCLC) is one of the most prevalent tumors with high incidence and mortality across the globe. Recently, increasing studies have demonstrated that circular RNAs (circRNAs) exert outstanding functions in NSCLC progression. Notwithstanding, we are still in the dark about the function and exact mechanism of circ-PITX1, a newly discovered circRNA. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) confirmed the profile of circ-PITX1 in NSCLC tissues and adjacent normal tissues. Gain- and loss- of function assay verified the impact of circ-PITX1 and miR-30e-5p on the proliferation, invasion, and migration of NSCLC cells (H1975 and A549). Bioinformatics analysis corroborated the downstream mechanisms of circ-PITX1. Dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) examined the interactions between circ-PITX1 and miR-30e-5p, miR-30e-5p and ITGA6. The protein levels of ITGA6, PI3K, AKT were determined by Western blot. circ-PITX1 was substantially up-regulated in NSCLC tissues and cells, and circ-PITX1 up-regulation was correlated with NSCLC patients' poor survival. Functionally, circ-PITX1 overexpression or miR-30e-5p inhibition markedly facilitated proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), reduced apoptosis, and enhanced ITGA6/PI3K/AKT expression in NSCLC cells, whereas circ-PITX1 knockdown or miR-30e-5p up-regulation resulted in the opposite results. Mechanistically, circ-PITX1 acted as a sponge of miR-30e-5p, which targeted the 3'untranslated region (UTR) of ITGA6. Knockdown of circ-PITX1 or overexpressing miR-30e-5p reduced ITGA6/PI3K/AKT axis. circ-PITX1 modulates the miR-30e-5p/ITGA6 axis to boost NSCLC progression, hence functioning as an oncogene.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Circular/genética , Proteínas de Arabidopsis , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/genética , Humanos , Integrina alfa6 , Neoplasias Pulmonares/patología , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt
16.
J Mater Chem C Mater ; 10(20): 7875-7885, 2022 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-35746953

RESUMEN

Environmental stability remains a major challenge for the commercialisation of organic solar cells and degradation pathways remain poorly understood. Designing materials for improved device stability requires an understanding of the relationship between the properties of the donor or acceptor molecule and different degradation mechanisms. Here we study the correlations between various molecular parameters of the fullerene derivative bis-PCBM and the degradation rate of polymer:bis-PCBM organic solar cells, based on the same carbazole-alt-benzothiadiazole polymer, in aerobic and anaerobic conditions. We compare eight high purity bis-PCBM isomers with different electronic, chemical and packing properties along with PCBM and the mixture of bis isomers. In the case of aerobic photodegradation, we find that device degradation rate is positively correlated to the LUMO energy of the bis-PCBM isomer and to the degree of crystallinity of the isomer, while the correlation of degradation with driving force for epoxide formation is unclear. These results support the idea that in these samples, aerobic photodegradation proceeds via superoxide formation by the photogenerated polaron on the fullerene, followed by further chemical reaction. In the absence of air, photodegradation rate is correlated with molecular structure, supporting the mechanism of microstructural degradation via fullerene dimerization. The approach and findings presented here show how control of specific molecular parameters through chemical design can serve as a strategy to enhance stability of organic solar cells.

17.
Int J Biol Sci ; 18(11): 4497-4512, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35864957

RESUMEN

YAP (gene symbol YAP1) as a potential oncoprotein, is positively correlated with the malignancy of various tumors. However, overexpression of YAP alone in multiple normal tissue cells has failed to induce tumor formation and the underlying mechanism is poorly understood. Herein, we show that YAP activation directly induces transcription of its negative regulator, SAV1, to constitute a negative feedback loop, which plays a vital role in maintaining lung epithelial cell homeostasis and was dysregulated in non-small cell lung cancer (NSCLC). Notably, smoking promotes the hypermethylation of the SAV1 promoter region, which disrupts YAP negative feedback by inactivating the Hippo pathway. Besides, exogenous overexpression of SAV1 can act as a traffic protein, activating the Hippo signaling and concurrently inhibiting the WNT pathway to decrease cancer cell growth. Furthermore, using the lung cancer organoids, we found that lentivirus-mediated SAV1 gene transfer combined with methylation inhibitor and YAP-TEAD inhibitor is a potential feasible clinical medication regimen for the lung cancer patient, especially among the smoking population. Thus, this SAV1 mediated feedback loop provides an efficient mechanism to establish the robustness and homeostasis of YAP regulation and as a potential target of gene therapy for the smoking NSCLC population.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Proteínas de Ciclo Celular , Neoplasias Pulmonares , Humo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Retroalimentación , Humanos , Neoplasias Pulmonares/genética , Fosfoproteínas/metabolismo , Regiones Promotoras Genéticas/genética , Humo/efectos adversos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
18.
Recent Pat Anticancer Drug Discov ; 17(4): 387-395, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35023460

RESUMEN

BACKGROUND: Therapeutic resistance is a frequent problem of cancer treatment and a leading cause of mortality in patients with metastatic colorectal cancer (CRC). Recent insight into the mechanisms that confer multidrug resistance has elucidated that the ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) assists cancer cells in escaping therapeutic stress caused by toxic chemotherapy. Therefore, it is necessary to develop ABCG2 inhibitors. OBJECTIVES: In the present study, we investigated the inhibitory effect of KU55933 on ABCG2 in CRC. METHODS: The cytotoxicity assay and drug accumulation assay were used to examine the inhibitory effect of KU55933 on ABCG2. The protein expressions were detected by Western blot assay. The docking assay was performed to predict the binding site and intermolecular interactions between KU55933 and ABCG2. RESULTS: KU55933 was more potent than the known ABCG2 inhibitor fumitremorgin C to enhance the sensitivity of mitoxantrone and doxorubicin and the intracellular accumulation of mitoxantrone, doxorubicin and rhodamine 123 inside CRC cells with ABCG2 overexpression. Moreover, KU55933 did not affect the protein level of ABCG2. Furthermore, the docking data showed that KU55933 was tightly located in the drug-binding pocket of ABCG2. CONCLUSION: In summary, our data presented that KU55933 could effectively inhibit the drug pump activity of ABCG2 in colorectal cancer, which is further supported by the predicted model that showed the hydrophobic interactions of KU55933 within the drug-binding pocket of ABCG2. KU55933 can potently inhibit the activity of ABCG2 in CRC.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Antineoplásicos , Neoplasias Colorrectales , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Humanos , Mitoxantrona/farmacología , Morfolinas/farmacocinética , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Pironas/farmacología
19.
Front Immunol ; 12: 680327, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34367140

RESUMEN

We present a patient with locoregionally advanced laryngeal carcinoma, who experienced recurrence 2 months after surgery. We exploratively treated this patient with immunotherapy combined with targeted therapy with or without radiation therapy. The patient exhibited a significant and durable response. Thus far, there are no standard or effective second-line therapeutic modalities for recurrent locoregionally advanced laryngeal carcinoma. The efficacy of conventional chemotherapy with anti-epidermal growth factor receptor (anti-EGFR) remains unsatisfactory. The addition of immunotherapy resulted in substantial improvement in the progression-free survival (PFS) and overall survival (OS) of this patient. In this case, immunotherapy combined with anti-EFGR was administered, leading to good tumor response; based on this observation, radiotherapy was added to further intensify tumor control. This therapeutic strategy may be a novel option for recurrent locoregionally advanced squamous cell carcinoma of the head and neck.


Asunto(s)
Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Antineoplásicos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Toma de Decisiones Clínicas , Terapia Combinada , Manejo de la Enfermedad , Humanos , Inmunoterapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Tomografía Computarizada por Rayos X
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