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1.
Nat Commun ; 15(1): 4664, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38821968

RESUMEN

Using a transfer printing technique, we imprint a layer of a designated near-infrared fluorescent dye BTP-eC9 onto a thin layer of Pt(II) complex, both of which are capable of self-assembly. Before integration, the Pt(II) complex layer gives intense deep-red phosphorescence maximized at ~740 nm, while the BTP-eC9 layer shows fluorescence at > 900 nm. Organic light emitting diodes fabricated under the imprinted bilayer architecture harvest most of Pt(II) complex phosphorescence, which undergoes triplet-to-singlet energy transfer to the BTP-eC9 dye, resulting in high-intensity hyperfluorescence at > 900 nm. As a result, devices achieve 925 nm emission with external quantum efficiencies of 2.24% (1.94 ± 0.18%) and maximum radiance of 39.97 W sr-1 m-2. Comprehensive morphology, spectroscopy and device analyses support the mechanism of interfacial energy transfer, which also is proved successful for BTPV-eC9 dye (1022 nm), making bright and far-reaching the prospective of hyperfluorescent OLEDs in the near-infrared region.

2.
Acta Pharmacol Sin ; 45(7): 1520-1529, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38519646

RESUMEN

Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-ß production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-ß inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1ß and p53, which accounts for the suppression of TGF-ß production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-ß/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.


Asunto(s)
Movimiento Celular , Neoplasias Hepáticas , Proteína Smad2 , Proteína smad3 , Factor de Crecimiento Transformador beta , Ubiquitina-Proteína Ligasas , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Transducción de Señal , Activación Transcripcional , Animales , Transición Epitelial-Mesenquimal , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Metástasis de la Neoplasia , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Ratones Desnudos , Ratones
3.
Front Pharmacol ; 14: 1072033, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37063257

RESUMEN

Despite the high mutation frequencies of KRAS, NRAS, and BRAF in colorectal cancer (CRC), there are no effective and reliable inhibitors for these biomarkers. Protocadherin-7 (PCDH7) is regarded as a potentially targetable surface molecule in cancer cells and plays an important role in their proliferation, metastasis, and drug resistance. However, the roles and underlying mechanisms of PCDH7 in CRC remain unclear. In the current study, we found that different colorectal cancer cells expressed PCDH7 over a wide range. The levels of PCDH7 expression were positively associated with cell proliferation and drug resistance in CRC cells but negatively correlated with the potential for cell migration and invasion. Our data indicated that PCDH7 mediated the resistance of CRC cells to ABT-263 (a small-molecule Bcl-2 inhibitor that induces apoptosis) by inhibiting cell apoptosis, which was supported by the downregulation of caspase-3, caspase-9, and PARP cleavage. We found that PCDH7 effectively promoted Mcl-1 expression at both mRNA and protein levels. Furthermore, PCDH7 activated the Wnt signaling pathway, which was confirmed by the increase in ß-catenin and c-Myc expression. Finally, and notably, S63845, a novel Mcl-1 inhibitor, not only effectively attenuated the inhibitory effect of PCDH7 on cell apoptosis induced by ABT-263 in vitro but also sensitized PCDH7-overexpressed CRC cell-derived xenografts to ABT-263 in vivo. Taken together, although PCDH7 inhibited the migration and invasion of CRC cells, it could facilitate the development of drug resistance in colorectal cancer cells by positively modulating Mcl-1 expression. The application of the Mcl-1 inhibitor S63845 could be a potential strategy for CRC chemotherapy, especially in CRC with high levels of PCDH7.

4.
Macromol Rapid Commun ; 44(2): e2200570, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36104160

RESUMEN

Fluorinated copolymers can self-assemble in solution and form micelles with rare properties due to the peculiar behavior of fluorinated groups. However, the process description of the self-assembly is still largely phenomenological and difficult to explain due to the tendency of the fluorinated segments to segregate from both the hydrophilic and lipophilic segments, which can result in various morphologies. Herein, the controlled formation of ellipsoidal micelles, disklike micelles, and sheets by hierarchical self-assembly of triphilic main-chain-type semifluorinated alternating graft copolymers (AB)n A-g-mOEG is presented (where A represents unit of α,ω-diiodoperfluoroalkane, B represents the unit of α,ω-unconjugated diene, and mOEG represents methoxy oligo(ethylene glycol)), which are synthesized by step transfer-addition and radical-termination (START) polymerization and azide-alkyne click chemistry. Furthermore, the possible self-assembly mechanism of these micron-level aggregates is proposed, which is ascribed to the hierarchical self-assembly, crowding effect of hydrophilic chains and the interfacial tension between the fluoroalkane and alkane segments. This study can provide a facile and highly efficient approach to the synthesis of main-chain-type fluorinated graft copolymers and expand the research field for the solution self-assembly of fluorinated copolymers.


Asunto(s)
Micelas , Polímeros , Polímeros/química , Agua/química , Polimerizacion , Interacciones Hidrofóbicas e Hidrofílicas
5.
Front Neurosci ; 17: 1305624, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38260009

RESUMEN

Background: Reduced brain volume, impaired cognition, and possibly a range of psychoneurological disorders have been reported in patients with non-alcoholic fatty liver disease (NAFLD); however, no underlying cause has been specified. Here, Mendelian randomization (MR) was employed to determine the causative NAFLD effects on cortical structure. Methods: We used pooled-level data from FinnGen's published genome-wide association study (GWAS) of NAFLD (1908 cases and 340,591 healthy controls), as well as published GWAS with NAFLD activity score (NAS) and fibrosis stage-associated SNPs as genetic tools, in addition to the Enigma Consortium data from 51,665 patients, were used to assess genetic susceptibility in relation to changes with cortical thickness (TH) and surface area (SA). A main estimate was made by means of inverse variance weighted (IVW), while heterogeneity and pleiotropy were detected using MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier to perform a two-sample MR analysis. Results: At the global level, NAFLD reduced SA (beta = -586.72 mm2, se = 217.73, p = 0.007) and several changes in the cortical structure of the cerebral gyrus were found, with no detectable pleiotropy. Conclusion: NAFLD causally affects cortical structures, which supports the presence of an intricate liver-brain axis.

6.
RSC Adv ; 12(46): 29677-29687, 2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36321091

RESUMEN

In this study, macroporous pH-sensitive poly[N-isopropylacrylamide-co-acrylic acid-sorbitan monooleate] hydrogels, termed as PNIPAM-co-AAc-Span80 hydrogels, with an enhanced hydrophobic property and a rich pore structure were prepared by free-radical polymerization in an ethanol/water mixture. The polymerizable surfactant AAc-Span80 was obtained by the esterification of acrylic acid (AAc) and sorbitan monooleate (Span80), which was used to copolymerize with N-isopropylacrylamide (NIPAM). The chemical structure, thermal stability, morphology, and amphipathy of the PNIPAM-co-AAc-Span80 hydrogels were characterized. The results showed that the polymerizable surfactant AAc-Span80 macromolecule introduced into the hydrogels could not only increase the hydrophobic property but also ameliorate the porous network morphology, which was conducive to high adsorption capacity for adriamycin hydrochloride (DOX). The adsorption results showed that the equilibrium adsorption capacity of DOX reached 467.5 mg g-1 within 48 h at pH 7.4, and the hydrophobic interactions and intermolecular hydrogen bonds were the main force in the adsorption process of DOX. The release results demonstrated that the macroporous pH-sensitive hydrogels loaded with DOX could release 98.7% of DOX at pH 5.0, which would be highly beneficial for the release of anti-cancer drugs in the environment of cancer cells. All the results demonstrate that the PNIPAM-co-AAc-Span80 hydrogels have great potential for the delivery of anti-cancer drugs.

7.
Macromol Rapid Commun ; 43(19): e2200266, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35792024

RESUMEN

Side-chain liquid crystalline polymer (SCLCP) usually contains a simple and flexible homopolymer as main chain, while its effect on the self-assembly behavior is often ignored. In this work, in order to increase the structural complexity and investigate the interaction between the main chain and mesogens, perfluorinated segments are introduced into the main chain using a photoinduced Step Transfer-Addition & Radical-Termination polymerization method, producing a novel series of SCLCPs containing 4-methoxyphenyl benzoate mesogens, soft hydrocarbon spacers, and a strictly alternating perfluoroalkyl and alkyl backbone. By adjusting the length of spacers or perfluoroalkyl segments, several mesophases with complex chain packing structures are achieved. This design strategy that constructing highly ordered liquid crystalline (LC) structures from SCLCPs with precise chemical structure provides a facile way toward novel LC nanomaterials.

8.
J Zhejiang Univ Sci B ; 23(4): 352, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35403390

RESUMEN

The online version of the original article can be found at https://doi.org/10.1631/jzus.B2000190 Erratum to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2020 21(10):779-795 https://doi.org/10.1631/jzus.B2000190.

9.
Chem Commun (Camb) ; 58(35): 5383-5386, 2022 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-35412535

RESUMEN

Introducing fluoroalkyl chains into metallopolymers is a prerequisite to studying the self-organization effect of fluoroalkyl chains and their structure-property relationship. In this work, we present a fluorinated metallopolymer to build an alternating conduction-insulation "molecular fence" model synthesized by the coordination of Ru(II) and a bis-terpyridine-end-capped-phenyl (BTP) ligand modified with fluoroalkyl chains. Taking advantage of scanning tunneling microscopy (STM), a well-aligned periodic linear layered structure is observed clearly, which provides the most direct visualization of the self-organization effect of fluoroalkyl chains for the first time. In addition, combining ultraviolet-visible (UV-vis) absorption spectroscopy and theoretical calculations, we find that fluoroalkyl chains demonstrate a septation effect between two adjacent metallopolymer chains and further restrain the occurrence of interchain charge-transfer transition (ICCT) due to their closed packed structure. This "molecular fence" model can provide a novel route for electron conduction in molecular networks and guide potential applications in the materials science field.

10.
Comput Struct Biotechnol J ; 20: 296-308, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35035784

RESUMEN

Transcription regulation in metazoa is controlled by the binding events of transcription factors (TFs) or regulatory proteins on specific modular DNA regulatory sequences called cis-regulatory modules (CRMs). Understanding the distributions of CRMs on a genomic scale is essential for constructing the metazoan transcriptional regulatory networks that help diagnose genetic disorders. While traditional reporter-assay CRM identification approaches can provide an in-depth understanding of functions of some CRM, these methods are usually cost-inefficient and low-throughput. It is generally believed that by integrating diverse genomic data, reliable CRM predictions can be made. Hence, researchers often first resort to computational algorithms for genome-wide CRM screening before specific experiments. However, current existing in silico methods for searching potential CRMs were restricted by low sensitivity, poor prediction accuracy, or high computation time from TFBS composition combinatorial complexity. To overcome these obstacles, we designed a novel CRM identification pipeline called regCNN by considering the base-by-base local patterns in TF binding motifs and epigenetic profiles. On the test set, regCNN shows an accuracy/auROC of 84.5%/92.5% in CRM identification. And by further considering local patterns in epigenetic profiles and TF binding motifs, it can accomplish 4.7% (92.5%-87.8%) improvement in the auROC value over the average value-based pure multi-layer perceptron model. We also demonstrated that regCNN outperforms all currently available tools by at least 11.3% in auROC values. Finally, regCNN is verified to be robust against its resizing window hyperparameter in dealing with the variable lengths of CRMs. The model of regCNN can be downloaded athttp://cobisHSS0.im.nuk.edu.tw/regCNN/.

11.
Sci Rep ; 11(1): 22695, 2021 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-34811424

RESUMEN

Animal hosts infected and killed by parasitoid fungi become nutrient-rich cadavers for saprophytes. Bacteria adapted to colonization of parasitoid fungi can be selected and can predominate in the cadavers, actions that consequently impact the fitness of the parasitoid fungi. In Taiwan, the zombie fungus, Ophiocordyceps unilateralis sensu lato (Clavicipitaceae: Hypocreales), was found to parasitize eight ant species, with preference for a principal host, Polyrhachis moesta. In this study, ant cadavers grew a fungal stroma that was predominated by Bacillus cereus/thuringiensis. The bacterial diversity in the principal ant host was found to be lower than the bacterial diversity in alternative hosts, a situation that might enhance the impact of B. cereus/thuringiensis on the sympatric fungus. The B. cereus/thuringiensis isolates from fungal stroma displayed higher resistance to a specific naphthoquinone (plumbagin) than sympatric bacteria from the environment. Naphthoquinones are known to be produced by O. unilateralis s. l., and hence the resistance displayed by B. cereus/thuringiensis isolates to these compounds suggests an advantage to B. cereus/thuringiensis to grow in the ant cadaver. Bacteria proliferating in the ant cadaver inevitably compete for resources with the fungus. However, the B. cereus/thuringiensis isolates displayed in vitro capabilities of hemolysis, production of hydrolytic enzymes, and antagonistic effects to co-cultured nematodes and entomopathogenic fungi. Thus, co-infection with B. cereus/thuringiensis offers potential benefits to the zombie fungus in killing the host under favorable conditions for reproduction, digesting the host tissue, and protecting the cadaver from being taken over by other consumers. With these potential benefits, the synergistic effect of B. cereus/thuringiensis on O. unilateralis infection is noteworthy given the competitive relationship of these two organisms sharing the same resource.


Asunto(s)
Hormigas/microbiología , Bacillus cereus/genética , Bacillus cereus/metabolismo , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Cadáver , Hypocreales/metabolismo , Animales , Hormigas/clasificación , Bacillus cereus/aislamiento & purificación , Bacillus thuringiensis/aislamiento & purificación , Biodiversidad , Caenorhabditis elegans/microbiología , Técnicas de Cocultivo , Coinfección , ADN Bacteriano/genética , Bosques , Especificidad del Huésped , Micelio/crecimiento & desarrollo , Micelio/metabolismo , Filogenia , Especificidad de la Especie , Simpatría , Taiwán
12.
Chem Commun (Camb) ; 57(86): 11354-11357, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34643625

RESUMEN

In this work, we report a much simpler and low-cost method to prepare main-chain-type semifluorinated alternating copolymers by the formation of a halogen bond (XB) complex between α,ω-diiodoperfluoroalkanes and amines/halide salts. It is interesting that the terminal iodine functional group of the polymer chains is easily lost in the amine-promoted system, while the loss can be significantly reduced by adding a small amount of water. Importantly, the system promoted by halide salts can ensure complete retention of the iodine functional group. Overall, the establishment of this method provides a new strategy for designing smart fluoropolymer materials in a green and environmentally friendly facile manner under irradiation with visible light at room temperature.

13.
Comput Struct Biotechnol J ; 19: 5149-5159, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34589189

RESUMEN

Transcript isoforms regulated by alternative splicing can substantially impact carcinogenesis, leading to a need to obtain clues for both gene differential expression and malfunctions of isoform distributions in cancer studies. The Cancer Genome Atlas (TCGA) project was launched in 2008 to collect cancer-related genome mutation raw data from the population. While many repositories tried to add insights into the raw data in TCGA, no existing database provides both comprehensive gene-level and isoform-level cancer stage marker investigation and survival analysis. We constructed Cancer DEIso to facilitate in-depth analyses for both gene-level and isoform-level human cancer studies. Patient RNA-seq data, sample sheets, patient clinical data, and human genome datasets were collected and processed in Cancer DEIso. And four functions to search differentially expressed genes/isoforms between cancer stages were implemented: (i) Search potential gene/isoform markers for a specified cancer type and its two stages; (ii) Search potentially induced cancer types and stages for a gene/isoform; (iii) Expression survival analysis on a given gene/isoform for some cancer; (iv) Gene/isoform stage expression comparison visualization. As an example, we demonstrate that Cancer DEIso can indicate potential colorectal cancer isoform diagnostic markers that are not easily detected when only gene-level expressions are considered. Cancer DEIso is available at http://cosbi4.ee.ncku.edu.tw/DEIso/.

14.
Mol Cancer Res ; 19(12): 2036-2045, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34462330

RESUMEN

Metastatic castration-resistant prostate cancer (mCRPC) includes a subset of patients with particularly unfavorable prognosis characterized by combined defects in at least two of three tumor suppressor genes: PTEN, RB1, and TP53 as aggressive variant prostate cancer molecular signature (AVPC-MS). We aimed to identify circulating tumor cells (CTC) signatures that could inform treatment decisions of patients with mCRPC with cabazitaxel-carboplatin combination therapy versus cabazitaxel alone. Liquid biopsy samples were collected prospectively from 79 patients for retrospective analysis. CTCs were detected, classified, enumerated through a computational pipeline followed by manual curation, and subjected to single-cell genome-wide copy-number profiling for AVPC-MS detection. On the basis of immunofluorescence intensities, detected rare cells were classified into 8 rare-cell groups. Further morphologic characterization categorized CTC subtypes from 4 cytokeratin-positive rare-cell groups, utilizing presence of mesenchymal features and platelet attachment. Of 79 cases, 77 (97.5%) had CTCs, 24 (30.4%) were positive for platelet-coated CTCs (pc.CTCs) and 25 (38.5%) of 65 sequenced patients exhibited AVPC-MS in CTCs. Survival analysis indicated that the presence of pc.CTCs identified the subset of patients who were AVPC-MS-positive with the worst prognosis and minimal benefit from combination therapy. In AVPC-MS-negative patients, its presence showed significant survival improvement from combination therapy. Our findings suggest the presence of pc.CTCs as a predictive biomarker to further stratify AVPC subsets with the worst prognosis and the most significant benefit of additional platinum therapy. IMPLICATIONS: HDSCA3.0 can be performed with rare cell detection, categorization, and genomic characterization for pc.CTC identification and AVPC-MS detection as a potential predictive biomarker of mCRPC.


Asunto(s)
Biomarcadores de Tumor/genética , Células Neoplásicas Circulantes/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Análisis de Supervivencia
15.
Biochem Biophys Res Commun ; 567: 22-28, 2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-34133998

RESUMEN

ABT-737, a small molecule BH-3 mimetic, is less effective against human colon cancers due to its resistance. Verticillin A is a natural compound, which was previously purified from verticillium-infected mushrooms. Hence, we aimed at overcoming the ABT737 resistance observed in CRC tumors by combining Verticillin A with ABT-737 and figuring out the potential mechanism. In this study, we observed that Verticillin A could sensitize colon cancer to ABT-737-induced cell death through induction of mitochondrial-dependent apoptosis. Verticillin A could significantly increase the BIMEL/MCL-1 ratio to overcome ABT737 resistance through the suppression of the MEK/ERK pathway. In addition, up-regulation of BIM protein levels to activate BAX translocation results in apoptosis induction. Altogether, our work suggested the potential application of Verticillin A as a MEK inhibitor in BH3-mimetic-based therapy.


Asunto(s)
Antineoplásicos/farmacología , Compuestos de Bifenilo/farmacología , Neoplasias del Colon/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Nitrofenoles/farmacología , Sulfonamidas/farmacología , Proteína 11 Similar a Bcl2/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/metabolismo , Humanos , Indoles/farmacología , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Piperazinas/farmacología
16.
Vet Res ; 52(1): 61, 2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926543

RESUMEN

Infectious bursal disease virus (IBDV) and fowl adenovirus serotype 4 (FAdV-4) cause infectious bursal disease (IBD) and hydropericardium-hepatitis syndrome, respectively. Recently, studies have reported co-infections of poultry with IBDV and FAdV-4, which is an important problem in the poultry industry. Here, the variant IBDV strain ZD-2018-1 and FAdV-4 isolate HB1501 were used to assess the pathogenicity of co-infection in 1-day-old specific pathogen-free (SPF) chickens. Compared with chickens infected with only FAdV-4, those coinfected with IBDV and FAdV-4 showed enhanced clinical symptoms, higher mortality, more severe tissue lesions, and higher biochemical index levels. Furthermore, the expression of interleukin (IL)-6, IL-1ß, and interferon-γ mRNAs in the IBDV-FAdV-4 coinfected chickens was delayed, and the antibody response levels were significantly lower in those birds compared with the FAdV-4-infected chickens. These results indicate that co-infection with variant IBDV ZD-2018-1 and FAdV-4 HB1501 could significantly promote the pathogenicity of FAdV-4 and reduce the immune response in chickens. This study provides the foundation for further investigation of the interaction mechanism in IBDV and FAdV-4 co-infection.


Asunto(s)
Infecciones por Birnaviridae/veterinaria , Pollos , Coinfección/veterinaria , Inmunidad Innata , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/mortalidad , Infecciones por Adenoviridae/inmunología , Infecciones por Adenoviridae/mortalidad , Infecciones por Adenoviridae/veterinaria , Animales , Aviadenovirus/fisiología , Infecciones por Birnaviridae/inmunología , Infecciones por Birnaviridae/mortalidad , Coinfección/inmunología , Coinfección/mortalidad , Virus de la Enfermedad Infecciosa de la Bolsa/fisiología , Organismos Libres de Patógenos Específicos
17.
ACS Macro Lett ; 10(5): 564-569, 2021 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-35570758

RESUMEN

In recent years, crystalline-driven self-assembly (CDSA) has received enormous attention, but almost only for block copolymers (BCPs). Herein, we introduced perfluorocarbon chains into main-chain-type liquid crystalline alternating copolymers (ACPs) to obtain perfluoroalkane-containing ACPs with periodic C-I bonds in polymer backbones via step transfer-addition and radical-termination (START) polymerization, followed by an iodine reduction reaction of C-I bonds to induce CDSA of ACPs and put forward a novel concept of "reduction-induced crystallization-driven self-assembly" (RI-CDSA) of main-chain-type ACPs for the first time. Finally, we proposed the folded-chain model and mechanism to explain the novel RI-CDSA behavior, and its rationality has been proved by the corresponding experimental results.

18.
J Zhejiang Univ Sci B ; 21(10): 779-795, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33043644

RESUMEN

Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Alk (containing parasitic fungi Hypomyces hyalines (Schw.) Tul.). Here, we initially found, by wound healing assay and Transwell assay in vitro, that verticillin A possesses an inhibitory effect against the migration and invasion of the human colon cancer cell. Subsequently, c-mesenchymal-epithelial transition factor (c-Met) was identified as a molecular target of verticillin A by screening key genes related to cell migration. Verticillin A-mediated c-Met suppression is at the transcriptional level. Further study demonstrated that verticillin A suppressed c-MET phosphorylation and decreased c-MET protein level. In addition, verticillin A inhibited the phosphorylation of c-MET downstream molecules including rat sarcoma (Ras)-associated factor (Raf), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT). Overexpression of Erk partially reversed the verticillin A-mediated anti-metastasis action in the human colon cancer cell. More importantly, verticillin A also inhibited cancer cell metastasis in vivo. Thus, verticillin A can significantly inhibit the migration and invasion of colon cancer cells by targeting c-Met and inhibiting Ras/Raf/mitogen-activated extracellular signal-regulated kinase (MEK)/ERK signaling pathways. Therefore, we determined that verticillin A is a natural compound that can be further developed as an anti-metastatic drug in human cancers.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-met/biosíntesis , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Indoles/farmacología , Ratones , Ratones Endogámicos BALB C , Invasividad Neoplásica , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Proteínas Proto-Oncogénicas c-raf/metabolismo , Interferencia de ARN , Cicatrización de Heridas , Proteínas ras/metabolismo
19.
Oncol Lett ; 20(2): 1360-1368, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32724378

RESUMEN

Cervical cancer is a malignant disease and a threat to women's health worldwide. Surgical resection followed by radiotherapy or chemotherapy is the main treatment strategy for cervical cancer; however, patients with cervical cancer, especially those with late-stage disease, may not benefit from these traditional therapies, which results in poor clinical outcome. ALOX12B is a gene encoding lipoxygenase, and a mutation in ALOX12B was detected in lung and breast cancer. Furthermore, ALOX12B is essential to the proliferation of epidermoid carcinoma cells; however, the role of ALOX12B in cervical cancer has not been studied thus far, to the best of our knowledge. In the present study, the expression levels of ALOX12B were reduced in cervical cancer cells by lentiviral transfection, and it was found that both cell proliferation and clone formation ability were significantly reduced, and the cell cycle was blocked at G1 phase. Tumor growth was also suppressed in vivo in a xenograft tumor model, but the migration of tumor cells was not affected by ALOX12B. Subsequently, using western blotting, it was demonstrated that knockdown of ALOX12B decreased the expression levels of PI3K, MEK1, ERK1, C-fos and cdc25. Meanwhile, overexpression of ALOX12B increased the expression levels of these five molecules. Conclusively, ALOX12B promoted cell proliferation in cervical cancer via regulation of the PI3K/ERK1 signaling pathway. The present study may improve our understanding of the molecular mechanisms underlying the function of ALOX12B in cervical cancer and inform new therapeutic strategies.

20.
Polymers (Basel) ; 12(5)2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-32455766

RESUMEN

Polymeric nanomaterials made from amphiphilic block copolymers are increasingly used in the treatment of tumor tissues. In this work, we firstly synthesized the amphiphilic block copolymer PBnMA-b-P(BAPMA-co-PEGMA) via reversible addition-fragmentation chain transfer (RAFT) polymerization using benzyl methacrylate (BnMA), poly (ethylene glycol) methyl ether methacrylate (PEGMA), and 3-((tert-butoxycarbonyl)amino)propyl methacrylate (BAPMA) as the monomers. Subsequently, PBnMA-b-P(APMA-co-PEGMA)@NIR 800 with photothermal conversion property was obtained by deprotection of the tert-butoxycarbonyl (BOC) groups of PBAPMA chains with trifluoroacetic acid (TFA) and post-modification with carboxyl functionalized ketocyanine dye (NIR 800), and it could self-assemble into micelles in CH3OH/water mixed solvent. The NIR photothermal conversion property of the post-modified micelles were investigated. Under irradiation with NIR light (λmax = 810 nm, 0.028 W/cm2) for 1 h, the temperature of the modified micelles aqueous solution increased to 53 °C from 20 °C, which showed the excellent NIR photothermal conversion property.

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