RESUMEN
4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin extracted from the fungus Ascochyta viciae, shows anticarcinogenic effects on various cancer cells. 5-Fluorouracil (5-FU) is used to treat colorectal cancer (CRC); however, its efficacy must be enhanced. In this study, we investigated the molecular mechanisms by which MAC acts synergistically with 5-FU to inhibit cell proliferation and induce apoptosis in CRC cells. MAC enhanced the cytotoxic effects of 5-FU by suppressing the Akt/mTOR/p70S6K and Wnt/ß-catenin signaling pathways. It also reduced the viability of 5-FU-resistant (5-FU-R) cells. Furthermore, expression of anti-apoptosis-related proteins and cancer stem-like cell (CSC) markers by 5-FU-R cells decreased in response to MAC. Similar to MAC, the knockdown of CTNNB1 induced apoptosis and reduced expression of mRNA encoding CRC markers in 5-FU-R cells. In summary, these results suggest that MAC and other ß-catenin modulators may be useful in overcoming the 5-FU resistance of CRC cells.
Asunto(s)
Apoptosis , Proliferación Celular , Neoplasias Colorrectales , Sinergismo Farmacológico , Fluorouracilo , Vía de Señalización Wnt , beta Catenina , Humanos , Fluorouracilo/farmacología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Vía de Señalización Wnt/efectos de los fármacos , Apoptosis/efectos de los fármacos , beta Catenina/metabolismo , beta Catenina/genética , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Homoleptic complexes [Fe(4bt)3](ClO4)2 (1), [Fe(2bt)3](ClO4)2 (2), and [Fe(3tpH)3](ClO4)2 (3) were obtained by a reaction between the Fe(II) precursor salt and the corresponding thiazole-based bidentate ligand (L = 4bt = 4,4'-bithiazole, 2bt = 2,2'-bithiazole, 3tpH = 3-(thiazol-2-yl)pyrazole). X-ray crystal structure determination revealed crystallization of solvent-free complex 1, a solvate 2·MeOH, and a co-crystal 3·2(3tpH). The crystal packing of all these complexes is dominated by one-dimensional interactions between the [Fe(L)3]2+ cations. These interactions are stronger in 2·MeOH and 3·2(3tpH), leading to cooperative and slightly hysteretic transitions between the high-spin and low-spin electronic configurations at â¼235 K and 159 K, respectively. In contrast, weaker intermolecular interactions in 1 result in a gradual spin crossover above 300 K, with the maximum fraction of the HS state â¼25% achieved at 400 K. Complexes 2 and 3·2(3tpH) exhibit light-induced excited spin state trapping (LIESST) under irradiation with white light or a 532 nm laser at 5 K. After the photoexcitation, the trapped metastable HS state relaxes to the ground LS state with the average relaxation temperature of 81 K and 68 K, respectively. Examination of the relaxation dynamics by optical absorption spectroscopy on a single crystal of 3·2(3tpH) revealed the sigmoidal shape of the relaxation curves at lower temperatures, attributed to cooperative effects, as well as a plateau at â¼10% of the HS fraction at intermediate temperatures, hinting at a more complex mechanism for the relaxation of the LIESST phase in this material.
RESUMEN
Background: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl2, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl2-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl2-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic.
RESUMEN
Computer modeling and simulation (CM&S) technology is widely used in the medical device industry due to its advantages such as reducing testing time and costs. However, the developer's parameter settings during the modeling and simulation process can have a significant impact on the results. This study developed a test model for the rotational shear strength of dental implants and the constraint force of total knee replacements based on CM&S technology and proposes ideal parameters to ensure reliability. For dental implants, the load area and sliding contact conditions were considered, and for total knee replacements, the friction coefficient, medial-lateral displacement, valgus-varus rotation, and elastic modulus were considered. By comparing the simulation results and mechanical tests, boundary conditions with an error rate of less than 1.5% were selected. When a jig (gripper and collector) was applied with the same boundary conditions, an error rate of 48~22% occurred; otherwise, it was confirmed that the error rate was within 10~0.2%. The FE model was verified with an error of 2.49 to 3% compared to the mechanical test. The friction coefficient variable had the greatest influence on the results, accounting for 10 to 13%, and it was confirmed that valgus-varus rotation had a greater influence on the results than medial-lateral displacement. Relatively, the elastic modulus of the insert had the least effect on the results. These research results are expected to make CM&S techniques useful as a medical device digital development tool (M3DT) in the development of total knee replacements and dental implants.
RESUMEN
Ferroelectric field-effect transistors (FeFETs) have attracted enormous attention for low-power and high-density nonvolatile memory devices in processing-in-memory (PIM). However, their small memory window (MW) and limited endurance severely degrade the area efficiency and reliability of PIM devices. Herein, we overcome such challenges using key approaches covering from the material to the device and array architecture. High ferroelectricity was successfully demonstrated considering the thermodynamics and kinetics, even in a relatively thick (≥30 nm) ferroelectric material that was unexplored so far. Moreover, we employed a metal-ferroelectric-metal-insulator-semiconductor architecture that enabled desirable voltage division between the ferroelectric and the metal-oxide-semiconductor FET, leading to a large MW (â¼11 V), fast operation speed (<20 ns), and high endurance (â¼1011 cycles) characteristics. Subsequently, reliable and energy-efficient multiply-and-accumulation (MAC) operations were verified using a fabricated FeFET-PIM array. Furthermore, a system-level simulation demonstrated the high energy efficiency of the FeFET-PIM array, which was attributed to charge-domain computing. Finally, the proposed signed weight MAC computation achieved high accuracy on the CIFAR-10 dataset using the VGG-8 network.
RESUMEN
A heteroleptic spin-crossover (SCO) complex, [Fe(tpma)(xnap-bim)](ClO4)2 (1; tpma = tris(2-pyridylmethyl)amine, xnap-bim = 8,15-dihydrodiimidazo[1,2-a:2',1'-c]naphtho[2,3-f][1,4]diazocine), has been obtained by reacting a Fe(II) precursor salt with tetradentate tpma and bidentate xnap-bim ligands. Depending on crystallization conditions, two different solvates have been obtained, 1·2.25py·0.5H2O and 1·py. The former readily loses the interstitial solvent to produce either a powder sample of 1 upon filtration or crystals of 1 if the solvent loss is slowed by placing the crystals of 1·2.25py·0.5H2O in diethyl ether. In contrast, 1·py exhibits higher stability toward solvent loss. The crystal packing of both solvates and of the solvent-free structure features double columns of [Fe(tpma)(xnap-bim)]2+ cations formed by efficient π-π interactions between the pyridyl groups of tpma ligands, as well as by stacks supported by π-π interactions between interdigitated naphthalene fragments of xnap-bim ligands. While both solvates show a gradual SCO between the high-spin (HS) and low-spin (LS) states of the Fe(II) ion, solvent-free complex 1 exhibits an abrupt spin transition centered at 127 K, with a narrow 2 K thermal hysteresis. Complex 1 also shows a light-induced excited spin state trapping effect, manifested as LS â HS conversion upon irradiation with white light at 5 K. The metastable HS state relaxes to the ground LS state when heated above 65 K.
RESUMEN
Cu(i) and Au(i) ions, capped with an N-heterocyclic carbene (NHC), react with (TMS)3P7 (TMS = trimethyl-silyl) to afford an η4-coordinated anion [NHCDippCu-P7(TMS)]- and a neutral trinuclear complex (NHCDippAu)3P7. Protecting the P7 cage with the TMS groups is instrumental in controlling the course of these reactions.
RESUMEN
Reactions between red phosphorus (Pred) and potassium ethoxide in various organic solvents under reflux convert this rather inert form of the element to soluble polyphosphides. The activation is hypothesized to proceed via a nucleophilic attack by ethoxide on the polymeric structure of Pred, leading to disproportionation of the latter, as judged from observation of P(OEt)3 in the reaction products. A range of solvents has been probed, revealing that different polyphosphide anions (P73-, P162-, P213-, and P5-) can be stabilized depending on the combination of the boiling point and dielectric constant (polarity) of the solvent. The effectiveness of activation also depends on the nature of nucleophile, with the rate of reaction between Pred and KOR increasing in the order t-Bu < n-Hex < Et < Me, which is in agreement with the increasing order of nucleophilic strength. Thiolates and amides were also examined as potential activators, but the reaction with these nucleophiles were substantially slower; nonetheless, all reactions between Pred and NaSR yielded exclusively P162- as a soluble polyphosphide product.
RESUMEN
Incorporation of a five-membered ring into a helicene framework disrupts aromatic conjugation and provides a site for selective deprotonation. The deprotonation creates an anionic cyclopentadienyl unit, switches on conjugation, leads to a >200â nm red-shift in the absorbance spectrum and injects a charge into a helical conjugated π-system without injecting a spin. Structural consequences of deprotonation were revealed via analysis of a monoanionic helicene co-crystallized with {K+ (18-crown-6)(THF)} and {Cs+ 2 (18-crown-6)3 }. UV/Vis-monitoring of these systems shows a time-dependent formation of mono- and dianionic species, and the latter was isolated and crystallographically characterized. The ability of the twisted helicene frame to delocalize the negative charge was probed as a perturbation of aromaticity using NICS scans. Relief of strain, avoidance of antiaromaticity, and increase in charge delocalization assist in the additional dehydrogenative ring closures that yield a new planarized decacyclic dianion.
RESUMEN
The nitroxyl radical 1-methyl-2-azaadamantane N-oxyl (Me-AZADO) exhibits magnetic bistability arising from a radical/dimer interconversion. The transition from the rotationally disordered paramagnetic plastic crystal, Me-AZADO, to the ordered diamagnetic crystalline phase, (Me-AZADO)2, has been conclusively demonstrated by crystal structure determination from high-resolution powder diffraction data and by solid-state NMR spectroscopy. The phase change is characterized by a wide thermal hysteresis with high sensitivity to even small applied pressures. The molecular dynamics of the phase transition from the plastic crystal to the conventional crystalline phase has been tracked by solid-state (1H and 13C) NMR and EPR spectroscopies.
RESUMEN
Ylidenemalononitrile enamines undergo rapid amine exchange followed by a cyclization with primary amines to yield fluorescent products with emission intensities as high as 900 times greater than the starting materials. After identifying the fluorescent species by X-ray crystallography, we demonstrate that the rate of amine exchange is substrate dependent and that by simple structural variation the fluorescence can be tuned over the entire visible spectrum. We further demonstrate their potential application in biomolecule labeling.
RESUMEN
Desilylation of silylethynyl-substituted benzobisoxazole cruciforms can be achieved using stoichiometric amounts of fluoride, leading to a significant change in their UV-vis absorption and fluorescence. This response is observable at micromolar concentrations of fluoride, and, in the case of a triisopropylsilyl-substituted cruciform fluorophore, extraordinarily selective for fluoride over other small inorganic anions, including hydroxide, acetate, and phosphate.
RESUMEN
OBJECTIVE: This study examined whether iron accumulated in ferritin-producing recombinant microbes is bioavailable to rats with iron deficiency. METHODS: Rats induced with iron deficiency were treated with iron preparations of ferrous ammonium sulfate, horse spleen ferritin, control yeast, and ferritin-producing recombinant yeast for 14 d. The bioavailability of iron was examined by measuring hemoglobin concentration, hematocrit value, and tissue iron stores. Differences between dietary groups were determined by one-way analysis of variance, and P < 0.05 was considered statistically significant. RESULTS: Based on hemoglobin concentration and hematocrit value, iron in ferrous ammonium sulfate, horse spleen ferritin, and ferritin-producing yeast were bioavailable to rats and cured iron deficiency. The efficacy of ferritin and ferritin-producing yeast was also confirmed in establishing tissue iron stores after induction of iron deficiency. CONCLUSIONS: The iron sources of ferritin and ferritin-producing yeast were as effective in recovery from iron deficiency as the iron compounds of ferric citrate and ferrous ammonium sulfate. The results suggest that the iron stored in the ferritin of recombinant yeast is bioavailable, and that recombinant yeast may contribute widely as a source of iron to resolve the global problem of iron deficiency.