Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 456
Filtrar
Más filtros

País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Nature ; 565(7737): 61-66, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30602749

RESUMEN

Topological quantum materials exhibit fascinating properties1-3, with important applications for dissipationless electronics and fault-tolerant quantum computers4,5. Manipulating the topological invariants in these materials would allow the development of topological switching applications analogous to switching of transistors6. Lattice strain provides the most natural means of tuning these topological invariants because it directly modifies the electron-ion interactions and potentially alters the underlying crystalline symmetry on which the topological properties depend7-9. However, conventional means of applying strain through heteroepitaxial lattice mismatch10 and dislocations11 are not extendable to controllable time-varying protocols, which are required in transistors. Integration into a functional device requires the ability to go beyond the robust, topologically protected properties of materials and to manipulate the topology at high speeds. Here we use crystallographic measurements by relativistic electron diffraction to demonstrate that terahertz light pulses can be used to induce terahertz-frequency interlayer shear strain with large strain amplitude in the Weyl semimetal WTe2, leading to a topologically distinct metastable phase. Separate nonlinear optical measurements indicate that this transition is associated with a symmetry change to a centrosymmetric, topologically trivial phase. We further show that such shear strain provides an ultrafast, energy-efficient way of inducing robust, well separated Weyl points or of annihilating all Weyl points of opposite chirality. This work demonstrates possibilities for ultrafast manipulation of the topological properties of solids and for the development of a topological switch operating at terahertz frequencies.

2.
J Am Chem Soc ; 146(4): 2333-2338, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38241610

RESUMEN

Odd-electron bonds, i.e., the two-center, three-electron (2c/3e), or one-electron (2c/1e) bonds, have attracted tremendous interest owing to their novel bonding nature and radical properties. Herein, complex [K(THF)6][LSn:···Sn:L] (1), featuring the first and unsupported 2c/1e Sn···Sn σ-bond with a long distance (3.2155(9) Å), was synthesized by reduction of stannylene [LSn:] (L = N,N-dpp-o-phenylene diamide) with KC8. The one-electron Sn-Sn bond in 1 was confirmed by the crystal structure, DFT calculations, EPR spectroscopy, and reactivity studies. This compound can be viewed as a stabilized radical by delocalizing to two metal centers and can readily mediate radical reactions such as C-C coupling of benzaldehyde.

3.
Small ; 20(7): e2304588, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37840413

RESUMEN

Current practices for delivering agrochemicals are inefficient, with only a fraction reaching the intended targets in plants. The surfaces of nanocarriers are functionalized with sucrose, enabling rapid and efficient foliar delivery into the plant phloem, a vascular tissue that transports sugars, signaling molecules, and agrochemicals through the whole plant. The chemical affinity of sucrose molecules to sugar membrane transporters on the phloem cells enhances the uptake of sucrose-coated quantum dots (sucQD) and biocompatible carbon dots with ß-cyclodextrin molecular baskets (suc-ß-CD) that can carry a wide range of agrochemicals. The QD and CD fluorescence emission properties allowed detection and monitoring of rapid translocation (<40 min) in the vasculature of wheat leaves by confocal and epifluorescence microscopy. The suc-ß-CDs more than doubled the delivery of chemical cargoes into the leaf vascular tissue. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that the fraction of sucQDs loaded into the phloem and transported to roots is over 6.8 times higher than unmodified QDs. The sucrose coating of nanoparticles approach enables unprecedented targeted delivery to roots with ≈70% of phloem-loaded nanoparticles delivered to roots. The use of plant biorecognition molecules mediated delivery provides an efficient approach for guiding nanocarriers containing agrochemicals to the plant vasculature and whole plants.


Asunto(s)
Plantas , Sacarosa , Transporte Biológico , Plantas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Agroquímicos , Hojas de la Planta
4.
J Virol ; 97(10): e0093823, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37792003

RESUMEN

IMPORTANCE: Human norovirus (HuNoV) is highly infectious and can result in severe illnesses in the elderly and children. So far, there is no effective antiviral drug to treat HuNoV infection, and thus, the development of HuNoV vaccines is urgent. However, NoV evolves rapidly, and currently, at least 10 genogroups with numerous genotypes have been found. The genetic diversity of NoV and the lack of cross-protection between different genotypes pose challenges to the development of broadly protective vaccines. In this study, guided by structural alignment between GI.1 and GII.4 HuNoV VP1 proteins, several chimeric-type virus-like particles (VLPs) were designed through surface-exposed loop grafting. Mouse immunization studies show that two of the designed chimeric VLPs induced cross-immunity against both GI.1 and GII.4 HuNoVs. To our knowledge, this is the first designed chimeric VLPs that can induce cross-immune activities across different genogroups of HuNoV, which provides valuable strategies for the development of cross-reactive HuNoV vaccines.


Asunto(s)
Infecciones por Caliciviridae , Epítopos , Genotipo , Norovirus , Vacunas Virales , Virión , Animales , Humanos , Ratones , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/virología , Epítopos/química , Epítopos/genética , Epítopos/inmunología , Inmunización , Norovirus/química , Norovirus/clasificación , Norovirus/genética , Norovirus/inmunología , Vacunas Virales/química , Vacunas Virales/genética , Vacunas Virales/inmunología , Quimera/genética , Quimera/inmunología , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Virión/química , Virión/genética , Virión/inmunología
5.
Spinal Cord ; 62(5): 207-213, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38454067

RESUMEN

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the potential of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG-3) renal scintigraphy for predicting maximal detrusor pressure in the early stages of spinal cord injury (SCI). SETTING: Tertiary rehabilitation facility. METHODS: Medical records of individuals with SCI admitted between January 2020 and April 2023 who underwent both 99mTc-MAG-3 renal scintigraphy and urodynamic study within 90 days of SCI onset were retrospectively reviewed. Pearson's coefficient analysis was performed to determine the relationship between 99mTc-MAG-3 renal scintigraphy findings and urodynamic study findings. A multivariate linear regression analysis was performed to determine the best predictors of maximal detrusor pressure. A multivariate logistic regression analysis was performed to determine risk factors for high detrusor pressure. RESULTS: Ninety-four participants were enrolled in this study. Pearson's correlation analysis showed that effective renal plasma flow (ERPF) and ERPF (% predicted) were significantly correlated with maximal detrusor pressure. The multivariate linear regression analysis demonstrated that ERPF (% predicted) was a significant predictor of maximal detrusor pressure. The multivariate logistic regression analysis showed that ERPF (% predicted) was significantly associated with high detrusor pressure. The receiver operating characteristic curve demonstrated that the predictive model had an area under the curve of 0.725, with an ERPF (% predicted) cut-off of 64.05%, sensitivity 1.000, and specificity 0.429. CONCLUSIONS: These results suggest that 99mTc-MAG-3 renal scintigraphy may be useful for predicting high detrusor pressure in early SCI and may guide the timing of urodynamic studies in individuals with early SCI for appropriate management of neurogenic lower urinary tract dysfunction.


Asunto(s)
Traumatismos de la Médula Espinal , Tecnecio Tc 99m Mertiatida , Urodinámica , Humanos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/complicaciones , Femenino , Masculino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Urodinámica/fisiología , Riñón/diagnóstico por imagen , Riñón/fisiopatología , Cintigrafía , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/diagnóstico por imagen , Vejiga Urinaria Neurogénica/fisiopatología , Radiofármacos , Anciano , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/fisiopatología
6.
Spinal Cord ; 62(1): 42-49, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38123747

RESUMEN

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the risk factors associated with dysphagia in individuals with cervical spinal cord injury (CSCI) and analyze the differences between individuals with improved penetration-aspiration (PA) and persistent PA on follow-up. SETTING: Tertiary inpatient rehabilitation facilities. METHODS: Medical records of individuals with CSCI admitted between December 2009 and February 2023 who underwent a videofluoroscopic swallowing study (VFSS) were retrospectively reviewed. Multivariate logistic regression analysis was performed to assess risk factors for dysphagia. Differences between individuals with improved PA and persistent PA were analyzed using an independent t-test. RESULTS: In total, 149 participants were enrolled. Age (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.04-1.12), percentage of forced vital capacity to predicted normal (FVC (% predicted)) (OR 0.90, 95% CI 0.85-0.94), and skeletal muscle index (OR 0.89, 95% CI, 0.79-0.99) were significant factors associated with the risk of PA. Based on the receiver operating characteristic curve analysis, the cut-off values for age, FVC (% predicted), and skeletal muscle index were determined as 56.0, 45.7, and 41.0, respectively. A secondary analysis of the follow-up VFSS was conducted on 38 participants. The follow-up FVC (% predicted) and degree of weight loss differed significantly between the improved PA and persistent PA groups. CONCLUSIONS: Older age, low FVC (% predicted), and low skeletal muscle index can be predictors of dysphagia in patients with CSCI. On follow-up VFSS, individuals with improved PA demonstrated greater improvement in FVC (% predicted).


Asunto(s)
Médula Cervical , Trastornos de Deglución , Trastornos Respiratorios , Sarcopenia , Traumatismos de la Médula Espinal , Humanos , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico por imagen , Estudios Retrospectivos , Sarcopenia/complicaciones , Médula Cervical/lesiones
7.
Int J Mol Sci ; 25(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38256178

RESUMEN

Unintended genetic modifications that occur during the differentiation and proliferation of human induced pluripotent stem cells (hiPSCs) can lead to tumorigenicity. This is a crucial concern in the development of stem cell-based therapies to ensure the safety and efficacy of the final product. Moreover, conventional genetic stability testing methods are limited by low sensitivity, which is an issue that remains unsolved. In this study, we assessed the genetic stability of hiPSCs and hiPSC-derived cardiomyocytes using various testing methods, including karyotyping, CytoScanHD chip analysis, whole-exome sequencing, and targeted sequencing. Two specific genetic mutations in KMT2C and BCOR were selected from the 17 gene variants identified by whole-exome and targeted sequencing methods, which were validated using droplet digital PCR. The applicability of this approach to stem cell-based therapeutic products was further demonstrated with associated validation according to the International Council for Harmonisation (ICH) guidelines, including specificity, precision, robustness, and limit of detection. Our droplet digital PCR results showed high sensitivity and accuracy for quantitatively detecting gene mutations, whereas conventional qPCR could not avoid false positives. In conclusion, droplet digital PCR is a highly sensitive and precise method for assessing the expression of mutations with tumorigenic potential for the development of stem cell-based therapeutics.


Asunto(s)
Células Madre Pluripotentes Inducidas , Humanos , Miocitos Cardíacos , Carcinogénesis , Diferenciación Celular/genética , Reacción en Cadena de la Polimerasa
8.
Angew Chem Int Ed Engl ; : e202408894, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830120

RESUMEN

Developing a desirable ethanol dehydrogenation process necessitates a highly efficient and selective catalyst with low cost. Herein, we show that the "complex active site" consisting of atomically dispersed Au atoms with the neighboring oxygen vacancies (Vo) and undercoordinated cation on oxide supports can be prepared and display unique catalytic properties for ethanol dehydrogenation. The "complex active site" Au-Vo-Zr3+ on Au1/ZrO2 exhibits the highest H2 production rate, with above 37,964 mol H2 per mol Au per hour (385 g H2 g-1 Au h-1) at 350 oC, which is 3.32, 2.94 and 15 times higher than Au1/CeO2, Au1/TiO2, and Au1/Al2O3, respectively. Combining experimental and theoretical studies, we demonstrate the structural sensitivity of these complex sites by assessing their selectivity and activity in ethanol dehydrogenation. Our study sheds new light on the design and development of cost-effective and highly efficient catalysts for ethanol dehydrogenation. Fundamentally, atomic-level catalyst design by colocalizing catalytically active metal atoms forming a structure-sensitive "complex site", is a crucial way to advance from heterogeneous catalysis to molecular catalysis. Our study advanced the understanding of the structure sensitivity of the active site in atomically dispersed catalysts.

9.
J Am Chem Soc ; 145(2): 811-821, 2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36596224

RESUMEN

The catalytic transformation of N2 to NH3 by transition metal complexes is of great interest and importance but has remained a challenge to date. Despite the essential role of vanadium in biological N2 fixation, well-defined vanadium complexes that can catalyze the conversion of N2 to NH3 are scarce. In particular, a V(NxHy) intermediate derived from proton/electron transfer reactions of coordinated N2 remains unknown. Here, we report a dinitrogen-bridged divanadium complex bearing POCOP (2,6-(tBu2PO)2-C6H3) pincer and aryloxy ligands, which can serve as a catalyst for the reduction of N2 to NH3 and N2H4. Low-temperature protonation and reduction of the dinitrogen complex afforded the first structurally characterized neutral metal hydrazido(2-) species ([V]═NNH2), which mediated 15N2 conversion to 15NH3, indicating that it is a plausible intermediate of the catalysis. DFT calculations showed that the vanadium hydrazido complex [V]═NNH2 possessed a N-H bond dissociation free energy (BDFEN-H) of as high as 59.1 kcal/mol. The protonation of a vanadium amide complex ([V]-NH2) with [Ph2NH2][OTf] resulted in the release of NH3 and the formation of a vanadium triflate complex, which upon reduction under N2 afforded the vanadium dinitrogen complex. These transformations model the final steps of a vanadium-catalyzed N2 reduction cycle. Both experimental and theoretical studies suggest that the catalytic reaction may proceed via a distal pathway to liberate NH3. These findings provide unprecedented insights into the mechanism of N2 reduction related to FeV nitrogenase.


Asunto(s)
Amoníaco , Vanadio , Amoníaco/química , Oxidación-Reducción , Nitrogenasa/metabolismo , Protones , Catálisis
10.
PLoS Pathog ; 17(7): e1009745, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34252166

RESUMEN

Norovirus (NoV) is the major pathogen causing the outbreaks of the viral gastroenteritis across the world. Among the various genotypes of NoV, GII.4 is the most predominant over the past decades. GII.4 NoVs interact with the histo-blood group antigens (HBGAs) to invade the host cell, and it is believed that the receptor HBGAs may play important roles in selecting the predominate variants by the nature during the evolution of GII.4 NoVs. However, the evolution-induced changes in the HBGA-binding affinity for the GII.4 NoV variants and the mechanism behind the evolution of the NoV-HBGA interactions remain elusive. In the present work, the virus-like particles (VLPs) of the representative GII.4 NoV stains epidemic in the past decades were expressed by using the Hansenula polymorpha yeast expression platform constructed by our laboratory, and then the enzyme linked immunosorbent assay (ELISA)-based HBGA-binding assays as well as the molecular dynamics (MD) simulations combined with the molecular mechanics/generalized born surface area (MMGBSA) calculations were performed to investigate the interactions between various GII.4 strains and different types of HBGAs. The HBGA-binding assays show that for all the studied types of HBGAs, the evolution of GII.4 NoVs results in the increased NoV-HBGA binding affinities, where the early epidemic strains have the lower binding activity and the newly epidemic strains exhibit relative stronger binding intensity. Based on the MD simulation and MMGBSA calculation results, a physical mechanism that accounts for the increased HBGA-binding affinity was proposed. The evolution-involved residue mutations cause the conformational rearrangements of loop-2 (residues 390-396), which result in the narrowing of the receptor-binding pocket and thus tighten the binding of the receptor HBGAs. Our experimental and computational studies are helpful for better understanding the mechanism behind the evolution-induced increasing of HBGA-binding affinity, which may provide useful information for the drug and vaccine designs against GII.4 NoVs.


Asunto(s)
Antígenos de Grupos Sanguíneos/metabolismo , Interacciones Huésped-Parásitos/fisiología , Norovirus/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Norovirus/genética , Acoplamiento Viral
11.
Environ Sci Technol ; 57(48): 19663-19677, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37948609

RESUMEN

A lack of mechanistic understanding of nanomaterial interactions with plants and algae cell walls limits the advancement of nanotechnology-based tools for sustainable agriculture. We systematically investigated the influence of nanoparticle charge on the interactions with model cell wall surfaces built with cellulose or pectin and performed a comparative analysis with native cell walls of Arabidopsis plants and green algae (Choleochaete). The high affinity of positively charged carbon dots (CDs) (46.0 ± 3.3 mV, 4.3 ± 1.5 nm) to both model and native cell walls was dominated by the strong ionic bonding between the surface amine groups of CDs and the carboxyl groups of pectin. In contrast, these CDs formed weaker hydrogen bonding with the hydroxyl groups of cellulose model surfaces. The CDs of similar size with negative (-46.2 ± 1.1 mV, 6.6 ± 3.8 nm) or neutral (-8.6 ± 1.3 mV, 4.3 ± 1.9 nm) ζ-potentials exhibited negligible interactions with cell walls. Real-time monitoring of CD interactions with model pectin cell walls indicated higher absorption efficiency (3.4 ± 1.3 10-9) and acoustic mass density (313.3 ± 63.3 ng cm-2) for the positively charged CDs than negative and neutral counterparts (p < 0.001 and p < 0.01, respectively). The surface charge density of the positively charged CDs significantly enhanced these electrostatic interactions with cell walls, pointing to approaches to control nanoparticle binding to plant biosurfaces. Ca2+-induced cross-linking of pectin affected the initial absorption efficiency of the positively charged CD on cell wall surfaces (∼3.75 times lower) but not the accumulation of the nanoparticles on cell wall surfaces. This study developed model biosurfaces for elucidating fundamental interactions of nanomaterials with cell walls, a main barrier for nanomaterial translocation in plants and algae in the environment, and for the advancement of nanoenabled agriculture with a reduced environmental impact.


Asunto(s)
Arabidopsis , Nanopartículas , Electricidad Estática , Celulosa/metabolismo , Plantas/metabolismo , Arabidopsis/metabolismo , Pectinas/metabolismo , Pared Celular/metabolismo
12.
Proc Natl Acad Sci U S A ; 117(47): 29442-29452, 2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33168744

RESUMEN

Employing liquid organic hydrogen carriers (LOHCs) to transport hydrogen to where it can be utilized relies on methods of efficient chemical dehydrogenation to access this fuel. Therefore, developing effective strategies to optimize the catalytic performance of cheap transition metal-based catalysts in terms of activity and stability for dehydrogenation of LOHCs is a critical challenge. Here, we report the design and synthesis of ultrasmall nickel nanoclusters (∼1.5 nm) deposited on defect-rich boron nitride (BN) nanosheet (Ni/BN) catalysts with higher methanol dehydrogenation activity and selectivity, and greater stability than that of some other transition-metal based catalysts. The interface of the two-dimensional (2D) BN with the metal nanoparticles plays a strong role both in guiding the nucleation and growth of the catalytically active ultrasmall Ni nanoclusters, and further in stabilizing these nanoscale Ni catalysts against poisoning by interactions with the BN substrate. We provide detailed spectroscopy characterizations and density functional theory (DFT) calculations to reveal the origin of the high productivity, high selectivity, and high durability exhibited with the Ni/BN nanocatalyst and elucidate its correlation with nanocluster size and support-nanocluster interactions. This study provides insight into the role that the support material can have both regarding the size control of nanoclusters through immobilization during the nanocluster formation and also during the active catalytic process; this twofold set of insights is significant in advancing the understanding the bottom-up design of high-performance, durable catalytic systems for various catalysis needs.

13.
Int J Mol Sci ; 24(12)2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37373174

RESUMEN

This study aimed to synthesize 23 coumarin derivatives and analyze their anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. A cytotoxicity test performed on LPS-induced RAW264.7 macrophages revealed that none of the 23 coumarin derivatives were cytotoxic. Among the 23 coumarin derivatives, coumarin derivative 2 showed the highest anti-inflammatory activity by significantly reducing nitric oxide production in a concentration-dependent manner. Coumarin derivative 2 inhibited the production of proinflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, and decreased the expression level of each mRNA. In addition, it inhibited the phosphorylation of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, nuclear factor kappa-B p65 (NF-κB p65), and inducible nitric oxide synthase. These results indicated that coumarin derivative 2 inhibited LPS-induced mitogen-activated protein kinase and NF-κB p65 signal transduction pathways in RAW264.7 cells, as well as proinflammatory cytokines and enzymes related to inflammatory responses, to exert anti-inflammatory effects. Coumarin derivative 2 showed potential for further development as an anti-inflammatory drug for the treatment of acute and chronic inflammatory diseases.


Asunto(s)
FN-kappa B , Piranocumarinas , Humanos , FN-kappa B/metabolismo , Piranocumarinas/uso terapéutico , Lipopolisacáridos/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/metabolismo , Citocinas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo
14.
Int J Mol Sci ; 24(18)2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37762259

RESUMEN

Currently, therapies for treating oral cancer have various side effects; therefore, research on treatment methods employing natural substances is being conducted. This study aimed to investigate piperine-induced apoptosis and autophagy in HSC-3 human oral cancer cells and their effects on tumor growth in vivo. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that piperine reduced the viability of HSC-3 cells and 4',6-diamidino-2-phenylindole staining, annexin-V/propidium iodide staining, and analysis of apoptosis-related protein expression confirmed that piperine induces apoptosis in HSC-3 cells. Additionally, piperine-induced autophagy was confirmed by the observation of increased acidic vesicular organelles and autophagy marker proteins, demonstrating that autophagy in HSC-3 cells induces apoptosis. Mechanistically, piperine induced apoptosis and autophagy by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in HSC-3 cells. We also confirmed that piperine inhibits oral cancer tumor growth in vivo via antitumor effects related to apoptosis and PI3K signaling pathway inhibition. Therefore, we suggest that piperine can be considered a natural anticancer agent for human oral cancer.

15.
Molecules ; 28(18)2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37764519

RESUMEN

Ten traditional herbal extracts effective against diarrhea, infectious diseases, and bacterial activity were selected and analyzed for Peyer's patch cell-mediated intestinal immunomodulatory activity in vitro and in vivo. Among the 10 herbal extracts, Zingiber officinale Rosc. (ZO) extract induced the highest secretion of immunoglobulin A (IgA) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cells of Peyer's patches. Furthermore, animal experiments showed that IA production was enhanced with the oral administration of ZO extract (100 mg/kg and 300 mg/kg) for 10 days. In addition, 6-, 8-, 10-gingerol, and 6-, 8-, 10-shogaol, the six major index compounds of ZO extract, were analyzed using HPLC. Our study findings confirm the intestinal immunomodulatory activity of ZO extract and lay a strong foundation for future analytical studies aimed at determining the active components of ZO extracts.

16.
J Cell Sci ; 133(1)2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31831524

RESUMEN

Store-operated Ca2+ entry (SOCE) is a major Ca2+ influx pathway that is controlled by the ER Ca2+ sensor STIM1. Abnormal activation of STIM1 directly influences Ca2+ influx, resulting in severe diseases such as Stormorken syndrome. The inactivation domain of STIM1 (IDstim) has been identified as being essential for Ca2+-dependent inactivation of STIM1 (CDI) after SOCE occurs. However, it is unknown whether IDstim is involved in keeping STIM1 inactive before CDI. Herein, we show that IDstim helps STIM1 keep inactive through intramolecular binding with the coiled-coil domain. Between IDstim and the coiled-coil domain, we found a short conserved linker whose extension or mutation leads to the constitutive activation of STIM1. We have demonstrated that IDstim needs the coiled-coil domain 1 (CC1) to inhibit the Ca2+ release-activated Ca2+ (CRAC) activation domain (CAD) activity and binds to a CC1-CAD fragment. Serial deletion of CC1 revealed that CC1α1 is a co-inhibitory domain of IDstim. CC1α1 deletion or leucine mutation, which abolishes the closed conformation, impaired the inhibitory effect and binding of IDstim. These results suggest that IDstim cooperates with CC1α1 to help STIM1 keep inactive under resting conditions.


Asunto(s)
Proteínas de Neoplasias/metabolismo , Molécula de Interacción Estromal 1/metabolismo , Calcio/metabolismo , Células HEK293 , Humanos , Conformación Proteica , Dominios Proteicos
17.
FASEB J ; 35(1): e21221, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33337564

RESUMEN

Alterations in complement component 3 (C3) expression has been reported to be linked to several bowel diseases including Crohn's disease, inflammatory bowel disease, and ulcerative colitis; however, the association with constipation has never been investigated. In this study, we aimed to investigate the correlation between C3 regulation and constipation development using a C3 deficiency model. To achieve these, alterations in stool excretion, transverse colon histological structure, and mucin secretion were analyzed in FVB/N-C3em1Hlee /Korl (C3 knockout, C3 KO) mice with the deletion of 11 nucleotides in exon 2 of the C3 gene. The stool excretion parameters, gastrointestinal transit, and intestine length were remarkably decreased in C3 KO mice compared with wild-type (WT) mice, although there was no specific change in feeding behavior. Furthermore, C3 KO mice showed a decrease in mucosal and muscle layer thickness, alterations in crypt structure, irregular distribution of goblet cells, and an increase of mucin droplets in the transverse colon. Mucin secretion was suppressed, and they accumulated in the crypts of C3 KO mice. In addition, the constipation phenotypes detected during C3 deficiency were confirmed in FVB/N mice treated with C3 convertase inhibitor (rosmarinic acid (RA)). Similar phenotypes were observed with respect to stool excretion parameters, gastrointestinal transit, intestine length, alterations in crypt structure, and mucin secretion in RA-treated FVB/N mice. Therefore, the results of the present study provide the first scientific evidence that C3 deficiency may play an important role in the development of constipation phenotypes in C3 KO mice.


Asunto(s)
Complemento C3/deficiencia , Estreñimiento/metabolismo , Exones , Animales , Cinamatos/farmacología , Complemento C3/metabolismo , Convertasas de Complemento C3-C5/antagonistas & inhibidores , Convertasas de Complemento C3-C5/genética , Convertasas de Complemento C3-C5/metabolismo , Estreñimiento/genética , Estreñimiento/patología , Depsidos/farmacología , Ratones , Ratones Noqueados , Ácido Rosmarínico
18.
Photodermatol Photoimmunol Photomed ; 38(6): 571-581, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35437847

RESUMEN

BACKGROUND: In this study, we examined cellular responses to acute and chronic IRA irradiation at mild and natural levels of exposure in two types of human fibroblasts, each isolated from a different donor, at physiological temperature (34°C). METHOD: Two types of human dermal fibroblasts (derived from a 20- and 50-year-old women, respectively) were exposed to different repeat numbers of IRA exposure (3, 6, 10, and 14 times; 42 mW/cm2 ) at a frequency of 3-4 times per week (4 h per irradiation). Cellular responses to acute and chronic IRA irradiation were examined by reactive oxygen species (ROS) level, apoptotic signals, cellular morphology, and collagen level. RESULTS: We demonstrated that chronic IRA irradiation-induced severe cellular damage, including prolonged cell proliferation, increased intracellular ROS levels, activated cellular apoptosis, and elongated cell morphology, whereas acute IRA irradiation had negligible effects at 34°C. In addition, it was evident that the degree of cellular damage due to IRA irradiation differed according to the type of fibroblasts. CONCLUSIONS: Considering the severe cellular damage induced by chronic IRA irradiation without heat, continuous exposure of skin to IRA irradiation during daily life may be harmful enough to induce photoaging.


Asunto(s)
Envejecimiento de la Piel , Enfermedades de la Piel , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Rayos Ultravioleta , Temperatura , Piel/metabolismo , Fibroblastos/metabolismo
19.
J Digit Imaging ; 35(6): 1590-1598, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35668218

RESUMEN

Several studies have investigated the relationship between the thickness of the posterior meniscofemoral ligament (pMFL) and the presence of a discoid meniscus. We investigated the correlation between meniscal pathology and anatomic features of pMFL such as attachment type, thickness, and volume. We retrospectively evaluated 191 patients who underwent knee MRI. MR images were reviewed to assess the attachment type of the pMFL on the medial femoral condyle (high vs. low), the thickness of the pMFL, and the presence of a meniscal tear or a discoid meniscus. The pMFL volume was quantified by using three-dimensional (3D) segmentation software. The relationship between the frequency of medial or lateral meniscal tear and anatomic features of pMFL were analyzed using Chi-square, Fisher's exact, or Mann-Whitney U test. High type pMFLs had significantly greater thickness and volume than low type pMFLs (p < 0.001). Patients with degenerative lateral meniscal tear had significantly higher thickness and volume of the pMFL than patients with intact lateral meniscus (p < 0.05). The pMFL thickness and volume were not significantly related to traumatic lateral meniscal tear, medial meniscal tear, and discoid meniscus. High type pMFLs tended to be thicker and larger than low type pMFLs and higher thickness and volume of the pMFL was significantly related to the degenerative lateral meniscal tear. However, the attachment type of the pMFL itself was not significantly related to the lateral meniscal tear as well as the medial meniscal tear.


Asunto(s)
Lesiones de Menisco Tibial , Humanos , Lesiones de Menisco Tibial/diagnóstico por imagen , Estudios Retrospectivos , Meniscos Tibiales/diagnóstico por imagen , Ligamentos Articulares/diagnóstico por imagen , Ligamentos Articulares/patología , Articulación de la Rodilla , Imagen por Resonancia Magnética/métodos
20.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36555388

RESUMEN

Chrysin is a flavonoid found abundantly in substances, such as honey and phytochemicals, and is known to exhibit anticancer effects against various cancer cells. Nevertheless, the anticancer effect of chrysin against oral cancer has not yet been verified. Furthermore, the mechanism underlying autophagy is yet to be clearly elucidated. Thus, this study investigated chrysin-mediated apoptosis and autophagy in human mucoepidermoid carcinoma (MC-3) cells. The change in MC-3 cell viability was examined using a 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide cell viability assay, as well as 40,6-diamidino-2-phenylindole, annexin V, and propidium iodide staining. Western blotting was used to analyze the proteins related to apoptosis and the mitogen-activated protein kinase (MAPK) pathway. In addition, the presence or absence of autophagy and changes in the expression of related proteins were investigated using acridine orange staining and Western blot. The results suggested that chrysin induced apoptosis and autophagy in MC-3 oral cancer cells via the MAPK/extracellular signal-regulated kinase pathway. Moreover, the induced autophagy exerted a cytoprotective effect against apoptosis. Thus, the further reduced cell viability due to autophagy as well as apoptosis induction highlight therapeutic potential of chrysin for oral cancer.


Asunto(s)
Apoptosis , Neoplasias de la Boca , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Flavonoides/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Autofagia , Línea Celular Tumoral , Neoplasias de la Boca/tratamiento farmacológico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA