RESUMEN
A wide variety of peptidomimetics (peptide analogs) possessing innovative biological functions have been brought forth as therapeutic candidates through cell-free protein synthesis (CFPS) systems. A key feature of these peptidomimetic drugs is the use of non-canonical amino acid building blocks with diverse biochemical properties that expand functional diversity. Here, we summarize recent technologies leveraging CFPS platforms to expand the reach of peptidomimetics drugs. We also offer perspectives on engineering the translational machinery that may open new opportunities for expanding genetically encoded chemistry to transform drug discovery practice beyond traditional boundaries.
RESUMEN
Motivated by the intricate mechanisms underlying biomolecule syntheses in cells that chemistry is currently unable to mimic, researchers have harnessed biological systems for manufacturing novel materials. Cell-free systems (CFSs) utilizing the bioactivity of transcriptional and translational machineries in vitro are excellent tools that allow supplementation of exogenous materials for production of innovative materials beyond the capability of natural biological systems. Herein, recent studies that have advanced the ability to expand the scope of biobased materials using CFS are summarized and approaches enabling the production of high-value materials, prototyping of genetic parts and modules, and biofunctionalization are discussed. By extending the reach of chemical and enzymatic reactions complementary to cellular materials, CFSs provide new opportunities at the interface of materials science and synthetic biology.
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Biología Sintética , Sistema Libre de CélulasRESUMEN
Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.
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Receptores Notch , Transducción de Señal , Transducción de Señal/fisiología , Receptores Notch/metabolismo , Oncogenes , Células Madre Neoplásicas/metabolismo , Unión ProteicaRESUMEN
The oncogenic role of nuclear LIM domain only 2 (LMO2) as a transcriptional regulator is well established, but its function in the cytoplasm is largely unknown. Here, we identified LMO2 as a cytoplasmic activator for signal transducer and activator of transcription 3 (STAT3) signaling in glioma stem cells (GSCs) through biochemical and bioinformatics analyses. LMO2 increases STAT3 phosphorylation by interacting with glycoprotein 130 (gp130) and Janus kinases (JAKs). LMO2-driven activation of STAT3 signaling requires the LDB1 protein and leads to increased expression of an inhibitor of differentiation 1 (ID1), a master regulator of cancer stemness. Our findings indicate that the cytoplasmic LMO2-LDB1 complex plays a crucial role in the activation of the GSC signaling cascade via interaction with gp130 and JAK1/2. Thus, LMO2-LDB1 is a bona fide oncogenic protein complex that activates either the JAK-STAT signaling cascade in the cytoplasm or direct transcriptional regulation in the nucleus.
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Glioma , Factor de Transcripción STAT3 , Proteínas Adaptadoras Transductoras de Señales , Receptor gp130 de Citocinas/metabolismo , Citoplasma/metabolismo , Proteínas de Unión al ADN/metabolismo , Glioma/genética , Glioma/metabolismo , Glicoproteínas/metabolismo , Humanos , Quinasas Janus/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Proteínas con Homeodominio LIM/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Factor de Transcripción STAT3/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Glioblastoma (GBM) is a refractory disease that has a highly infiltrative characteristic. Over the past decade, GBM perivascular niche (PVN) has been described as a route of dissemination. Here, we investigated that trailed membrane structures, namely retraction fibers (RFs), are formed by perivascular extracellular matrix (ECM) proteins. By using the anatomical GBM database, we validated that the ECM-related genes were highly expressed in the cells within the PVN where fibronectin (FN) induced RF formation. By disrupting candidates of FN-binding integrins, integrin α5ß1 was identified as the main regulator of RF formation. De novo RFs were produced at the trailing edge, and focal adhesions were actively localized in RFs, indicating that adhesive force makes RFs remain at the bottom surface. Furthermore, we observed that GBM cells more frequently migrated along the residual RFs formed by preceding cells in microfluidic channels in comparison to those in the channels without RFs, suggesting that the infiltrative characteristics GBM could be attributed to RFs formed by the preceding cells in concert with chemoattractant cues. Altogether, we demonstrated that shedding membrane structures of GBM cells are maintained by FN-integrin α5ß1 interaction and promoted their motility .
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Neoplasias Encefálicas/metabolismo , Movimiento Celular , Fibronectinas/metabolismo , Glioblastoma/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Vitronectina/metabolismo , Animales , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Glioblastoma/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones DesnudosRESUMEN
The development of high efficiency dye-sensitized solar cells (DSSCs) has received tremendous attention. Many researchers have introduced new materials for use in DSSCs to achieve high efficiency. In this study, the change in power conversion efficiency (PCE) of DSSCs was investigated by introducing two types of materials-Au nanoparticles (Au NPs) and a scattering layer. A DSSC fabricated without neither Au NPs nor a scattering layer achieved a PCE of 5.85%. The PCE of a DSSC based on freestanding TiO2 nanotube arrays (f-TNTAs) with Au NPs was 6.50% due to better electron generation because the plasmonic absorption band of Au NPs is 530 nm, which matches the dye absorbance. Thus, more electrons were generated at 530 nm, which affected the PCE of the DSSC. The PCE of DSSCs based on f-TNTAs with a scattering layer was 6.61% due to better light harvesting by scattering. The scattering layer reflects all wavelengths of light that improve the light harvesting in the active layer in DSSCs. Finally, the PCE of DSSCs based on the f-TNTAs with Au NPs and a scattering layer was 7.12% due to the synergy of better electron generation and light harvesting by plasmonics and scattering. The application of Au NPs and a scattering layer is a promising research area for DSSCs as they can increase the electron generation and light harvesting ability.
RESUMEN
Dye-sensitized solar cells (DSSCs) are fabricated with freestanding TiO2 nanotube arrays (TNTAs) which are incorporated with Au nanoparticles (NPs) and carbon materials via electrodeposition and chemical vapor deposition (CVD) method to create a plasmonic effect and better electron transport that will enhance their energy conversion efficiency (ECE). The ECE of DSSCs based on the freestanding TNTAs is 5.87%. The ECE of DSSCs, based on the freestanding TNTAs with Au NPs or carbon materials, is 6.57% or 6.59%, respectively, and the final results of DSSCs according to the freestanding TNTAs with Au NPs and carbon materials is increased from 5.87% to 7.24%, which is an enhancement of 23.34% owing to plasmonic effect and better electron transport. Au NPs are incorporated into the channel of freestanding TNTAs and are characterized by CS-corrected-field emission transmission electron microscope (Cs-FE-TEM) and elemental mapping. Carbon materials are also well-incorporated in the channel of freestanding TNTAs and are analyzed by Raman spectroscopy.
RESUMEN
OBJECTIVES: Impedance cardiography (ICG) is a noninvasive technique that provides reasonably accurate measurements of cardiac output, but the usefulness of ICG in patients undergoing open abdominal surgery has not been validated. METHODS: Cardiac output was measured while patients underwent open gastrectomy using an ICG monitor (niccomo™; ICG-CO); the results were compared with those measured using a FloTrac™/Vigileo™ monitor (Flo-CO), which measures cardiac output by analysing the arterial waveform. Data collection commenced at the beginning of anaesthetic induction and continued until the patient was awake. Data were compared using the Bland-Altman analysis, and the clinical significance of the difference between the two methods was evaluated by calculating the percentage error (%). RESULTS: Eleven patients were monitored during surgery. The bias of the Flo-CO and ICG-CO values was -0.45 l/min. The upper and lower limits of agreement were 0.96 l/min and -1.85 l/min, respectively. The percentage error was 28.5%. Electrocautery induced interference that transiently impaired the performance of the ICG monitor. CONCLUSIONS: ICG provided useful information in evaluating the cardiac output of patients during abdominal surgery.