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This study evaluated the probiotic properties, safety profile, and antioxidative and immune system-enhancing effects of Enterococcus faecium strains isolated from human infant feces. E. faecium KU22001, E. faecium KU22002, and E. faecium KU22005 exhibited potential probiotic properties; however, to eliminate concerns about toxin production and antibiotic resistance, the E. faecium strains were heat-treated prior to experimental usage. E. faecium KU22001 showed the highest antioxidant activity and lowest reactive oxygen species production among the three strains. The immune system-enhancing effects of heat-killed E. faecium strains were evaluated using a nitric oxide assay. E. faecium KU22001 induced an increase in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in RAW 264.7 cells. Furthermore, E. faecium KU22001 activated the mitogen-activated protein kinase pathway, which was a key regulator of the immune system. These results demonstrate the potential use of E. faecium KU22001 as a multifunctional food material.
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Microsatellite instability (MSI) is a hypermutable condition caused by DNA mismatch repair system defects, contributing to the development of various cancer types. Recent research has identified Werner syndrome ATP-dependent helicase (WRN) as a promising synthetic lethal target for MSI cancers. Herein, we report the first discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for MSI cancer therapy. Initial computational analysis and biological evaluation identified a new scaffold for a WRN inhibitor. Subsequent SAR study led to the discovery of a highly potent WRN inhibitor. Furthermore, we demonstrated that the optimal compound induced DNA damage and apoptotic cell death in MSI cancer cells by inhibiting WRN. This study provides a new pharmacophore for WRN inhibitors, emphasizing their therapeutic potential for MSI cancers.
Asunto(s)
Inestabilidad de Microsatélites , Neoplasias , Tiofenos , Humanos , Ciclohexanonas , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Helicasa del Síndrome de Werner/antagonistas & inhibidores , Helicasa del Síndrome de Werner/metabolismo , Tiofenos/química , Tiofenos/farmacologíaRESUMEN
An isotope-selective responsive system based on molecular recognition in porous materials has potential for the storage and purification of isotopic mixtures but is considered unachievable because of the almost identical physicochemical properties of the isotopes. Herein, a unique isotope-responsive breathing transition of the flexible metal-organic framework (MOF), MIL-53(Al), which can selectively recognize and respond to only D2 molecules through a secondary breathing transition, is reported. This novel phenomenon is examined using in situ neutron diffraction experiments under the same conditions for H2 and D2 sorption experiments. This work can guide the development of a novel isotope-selective recognition system and provide opportunities to fabricate flexible MOF systems for energy-efficient purification of the isotopic mixture.
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The anti-cancer effects of heat-killed Enterococcus faecium KU22001 (KU22001), KU22002, and KU22005 isolated from human infant feces were investigated. The anti-proliferative activity of these strains against various cancer cell lines was evaluated using the MTT assay. To determine the production of exopolysaccharides (EPS) with potential anti-cancer effect, ethanol precipitation and phenol-sulfuric acid method was used with the cell free supernatant of strains grown at 25°C or 37°C. The EPS yield of E. faecium strains was higher at 25°C than at 37°C. Among these E. faecium strains, KU22001 grown at 25°C was associated with the highest bax/bcl-2 ratio, effective apoptosis rate, cell cycle arrest in the G0/G1 phase, and condensation of the nucleus in the cervical cancer HeLa cell line. In conclusion, these results suggest that KU22001 can be beneficial owing to the anti-cancer effects and production of functional materials, such as EPS.
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Antineoplásicos , Apoptosis , Enterococcus faecium , Calor , Humanos , Células HeLa , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Heces/microbiología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Línea Celular Tumoral , Puntos de Control del Ciclo Celular/efectos de los fármacos , TemperaturaRESUMEN
Because of their designability and unprecedented synergistic effects, core-shell metal-organic frameworks (MOFs) have been actively examined recently. However, the synthesis of single-crystalline core-shell MOFs is very challenging, and thus a limited number of examples have been reported. Here, we suggest a method of synthesizing single-crystalline HKUST-1@MOF-5 core-shells, which is HKUST-1 at the center of MOF-5. Through the computational algorithm, this pair of MOFs was predicted to have the matched lattice parameters and chemical connection points at the interface. To construct the core-shell structure, we prepared the octahedral- and cubic-shaped HKUST-1 crystals as a core MOF, in which the (111) and (001) facets were mainly exposed, respectively. Via the sequential reaction, the MOF-5 shell was well-grown on the exposed surface, showing a seamless connect interface, which resulted in the successful synthesis of single-crystalline HKUST-1@MOF-5. Their pure phase formation was proved by optical microscopic images and powder X-ray diffraction (PXRD) patterns. This method presents the potential of and insights into the single-crystalline core-shell synthesis with different kinds of MOFs.
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Estructuras Metalorgánicas , Algoritmos , Microscopía , PolvosRESUMEN
MOF-on-MOF is attracting great attention due to its improved and/or synergistic properties not exhibited in a single MOF. In particular, the non-isostructural pairs of MOF-on-MOFs can have great potential induced by large heterogeneity, which enables diverse applications in a wide range of fields. HKUST-1@IRMOF is a fascinating platform because the alteration of the IRMOF pores with bulkier substituent groups on the ligands can provide a more microporous environment. However, the sterically hindered linker can affect the seamless growth at the interface, an important issue in practical research fields. Despite many efforts to reveal the growth of a MOF-on-MOF, there is still a lack of studies on a MOF-on-MOF consisting of a sterically hindered interface. Indeed, the effect of a bulky linker at an interface of HKUST-1@IRMOF, a non-isostructural MOF-on-MOF system, has not yet been reported, and thus, how the interfacial strain affects the interfacial growth remains unknown. In this study, we investigate the effect of an interfacial strain on a chemical connection point in an MOF-on-MOF system through a series of theoretical and synthetic experiments using a HKUST-1@IRMOF system. Our results reveal the importance of the proximity of each coordinating site at a MOF-on-MOF interface as well as lattice parameter matching for an effective secondary growth to achieve a well-connected MOF-on-MOF.
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Hydrogen isotope separation with nanoporous materials is a very challenging yet promising approach. To overcome the limitation of the conventional isotope separation strategy, quantum sieving-based separation using nanoporous materials has been investigated recently. In this study, to see the thermodynamic deuterium separation phenomena attributed to the chemical affinity quantum sieving effect, we examine Hofmann-type metal-organic frameworks (MOFs), Co(pyz)[M(CN)4] (pyz = pyrazine, M = Pd2+, Pt2+, and Ni2+), which have microporosity (4.0 × 3.9 Å2) and an extraordinarily high density of open metal sites (â¼9 mmol/cm3). Owing to the preferential adsorption of D2 over H2 at strongly binding open metal sites, the Hofmann-type MOF, Co(pyz)[Pd(CN)4] exhibited a high selectivity (SD2/H2) of 21.7 as well as a large D2 uptake of 10 mmol/g at 25 K. This is the first study of Hofmann-type MOFs to report high selectivity and capacity, both of which are important parameters for the practical application of porous materials toward isotope separation.
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Composite metal-organic frameworks (MOFs) tend to possess complex interfaces that prevent facile and rational design. Here we present a joint computational/experimental workflow that screens thousands of MOFs and identifies the optimal MOF pairs that can seamlessly connect to one another by taking advantage of the fact that the metal nodes of one MOF can form coordination bonds with the linkers of the second MOF. Six MOF pairs (HKUST-1@MOF-5, HKUST-1@IRMOF-18, UiO-67@HKUST-1, PCN-68@MOF-5, UiO-66@MIL-88B(Fe) and UiO-67@MIL-88C(Fe)) yielded from our theoretical predictions were successfully synthesized, leading to clean single crystalline MOF@MOF, demonstrating the power of our joint workflow. Our work can serve as a starting point to accelerate the discovery of novel MOF composites that can potentially be used for many different applications.