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1.
Nat Commun ; 15(1): 7624, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223157

RESUMEN

Metal-oxide interfaces with poor coherency have specific properties comparing to bulk materials and offer broad applications in heterogeneous catalysis, battery, and electronics. However, current understanding of the three-dimensional (3D) atomic metal-oxide interfaces remains limited because of their inherent structural complexity and the limitations of conventional two-dimensional imaging techniques. Here, we determine the 3D atomic structure of metal-oxide interfaces in zirconium-zirconia nanoparticles using atomic-resolution electron tomography. We quantitatively analyze the atomic concentration and the degree of oxidation, and find the coherency and translational symmetry of the interfaces are broken. Atoms at the interface have low structural ordering, low coordination, and elongated bond length. Moreover, we observe porous structures such as Zr vacancies and nano-pores, and investigate their distribution. Our findings provide a clear 3D atomic picture of metal-oxide interface with direct experimental evidence. We anticipate this work could encourage future studies on fundamental problems of oxides, such as interfacial structures in semiconductor and atomic motion during oxidation process.

2.
Front Immunol ; 15: 1393404, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39206183

RESUMEN

Objective: To systematically evaluate the efficacy and safety of anlotinib targeted therapy for the treatment of patients with advanced digestive system neoplasms (DSNs). Methods: Clinical trials were extracted from PubMed, the Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and the Wanfang database up to October 2023. Outcome measures, including therapeutic efficacy, quality of life (QOL) and adverse events, were extracted and evaluated. Results: Twenty trials, including 1,613 advanced DSNs patients, were included. The results indicated that, compared with conventional treatment alone, the combination of anlotinib targeted therapy with conventional treatment significantly improved the patients' 6-months overall survival (OS, OR=1.76, CI=1.53 to 2.02, P<0.00001), overall response (ORR, OR=1.76, CI=1.53 to 2.02, P<0.00001) and disease control rate (DCR, OR=1.51, 95% CI=1.25 to 1.84, P<0.0001). Moreover, the group that received the combined therapy had higher rates of hypertension (P<0.00001), proteinuria (P<0.00001), fatigue (P<0.00001), diarrhea (P<0.00001), hypertriglyceridemia (P=0.02), alanine aminotransfease (ALT)increased (P=0.004), aspartate transaminase (AST) increased (P=0.006), anorexia (P<0.00001), weight loss (P=0.002), abdominal pain (P=0.0006), hypothyroidism (P=0.02), prolonged QT interval (P=0.04). Analyses of other adverse events, such as gastrointestinal reaction, leukopenia, and neutropenia, did not reveal significant differences (P>0.05). Conclusion: The combination of anlotinib targeted therapy and conventional treatment is more effective for DSNs treatment than conventional treatment alone. However, this combined treatment could lead to greater rates of hypertension, albuminuria and hand-foot syndrome. Therefore, the benefits and risks should be considered before treatment.


Asunto(s)
Neoplasias del Sistema Digestivo , Indoles , Inhibidores de Proteínas Quinasas , Quinolinas , Humanos , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Indoles/uso terapéutico , Indoles/efectos adversos , Indoles/administración & dosificación , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Resultado del Tratamiento , Calidad de Vida , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico
3.
Vaccines (Basel) ; 12(8)2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39203975

RESUMEN

The enormous effects of avian influenza on poultry production and the possible health risks to humans have drawn much attention to this disease. The H9N2 subtype of avian influenza virus is widely prevalent among poultry, posing a direct threat to humans through infection or by contributing internal genes to various zoonotic strains of avian influenza. Despite the widespread use of H9N2 subtype vaccines, outbreaks of the virus persist due to the rapid antigenic drift and shifts in the influenza virus. As a result, it is critical to develop a broader spectrum of H9N2 subtype avian influenza vaccines and evaluate their effectiveness. In this study, a recombinant baculovirus expressing the broad-spectrum HA protein was obtained via bioinformatics analysis and a baculovirus expression system (BES). This recombinant hemagglutinin (HA) protein displayed cross-reactivity to positive sera against several subbranch H9 subtype AIVs. An adjuvant and purified HA protein were then used to create an rHA vaccine candidate. Evaluation of the vaccine demonstrated that subcutaneous immunization of the neck with the rHA vaccine candidate stimulated a robust immune response, providing complete clinical protection against various H9N2 virus challenges. Additionally, virus shedding was more effectively inhibited by rHA than by the commercial vaccine. Thus, our findings illustrate the efficacy of the rHA vaccine candidate in shielding chickens against the H9N2 virus challenge, underscoring its potential as an alternative to conventional vaccines.

4.
ACS Appl Mater Interfaces ; 16(33): 43806-43815, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39105741

RESUMEN

Due to the large volume of exposed atoms and electrons at the surface of two-dimensional materials, interfacial charge coupling has been proven as an efficient strategy to engineer the electronic structures of two-dimensional materials assembled in van der Waals heterostructures. Recently, heterostructures formed by graphene stacked with CrOCl have demonstrated intriguing quantum states, including a distorted quantum Hall phase in the monolayer graphene and the unconventional correlated insulator in the bilayer graphene. Yet, the understanding of the interlayer charge coupling in the heterostructure remains challenging. Here, we demonstrate clear evidences of efficient hole doping in the interfacial-coupled graphene/CrOCl heterostructure by detailed Raman spectroscopy and electrical transport measurements. The observation of significant blue shifts and stiffness of graphene Raman modes quantitatively determines the concentration of hole injection of about 1.2 × 1013 cm-2 from CrOCl to graphene, which is highly consistent with the enhanced conductivity of graphene. First-principles calculations based on density functional theory reveal that due to the large work function difference and the electronegativity of Cl atoms in CrOCl, the electrons are efficiently transferred from graphene to CrOCl, leading to hole doping in graphene. Our findings provide clues for understanding the exotic physical properties of graphene/CrOCl heterostructures, paving the way for further engineering of quantum electronic states by efficient interfacial charge coupling in van der Waals heterostructures.

5.
ACS Nano ; 18(34): 23508-23517, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39137306

RESUMEN

Two-dimensional ferromagnetic/antiferromagnetic (2D-FM/AFM) heterostructures are of great significance to realize the application of spintronic devices such as miniaturization, low power consumption, and high-density information storage. However, traditional mechanical stacking can easily damage the crystal quality or cause chemical contamination residues for 2D materials, which can result in weak interface coupling and difficulty in device regulation. Chemical vapor deposition (CVD) is an effective way to achieve a high-quality heterostructure interface. Herein, high-quality interface 2D-FM/AFM Cr7Te8/MnTe vertical heterostructures were successfully synthesized via a one-pot CVD method. Moreover, the atomic-scale structural scanning transmission electron microscope (STEM) characterization shows that the interface of the vertical heterostructure is clear and flat without an excess interface layer. Compared to the parent Cr7Te8, the coercivity (HC) of the high-quality interface Cr7Te8/MnTe heterostructure is significantly reduced as the thickness of MnTe increases, with a maximum decrease of 74.5% when the thickness of the MnTe nanosheet is around 30 nm. Additionally, the HC of the Cr7Te8/MnTe heterostructure can also be regulated by applying a gate voltage, and the HC increases or decreases with increasing positive or negative gate voltages. Thus, the effective regulation of HC is essential to improving the performance of advanced spintronic devices (e.g., MRAM and magnetic sensors). Our work will provide ideas for spin controlling and device application of 2D-FM/AFM heterostructures.

6.
iScience ; 27(7): 110256, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39109174

RESUMEN

We examined the function of heparan-sulfate-modified proteoglycans (HSPGs) in pathways affecting Alzheimer disease (AD)-related cell pathology in human cell lines and mouse astrocytes. Mechanisms of HSPG influences on presenilin-dependent cell loss were evaluated in Drosophila using knockdown of the presenilin homolog, Psn, together with partial loss-of-function of sulfateless (sfl), a gene specifically affecting HS sulfation. HSPG modulation of autophagy, mitochondrial function, and lipid metabolism were shown to be conserved in human cell lines, Drosophila, and mouse astrocytes. RNA interference (RNAi) of Ndst1 reduced intracellular lipid levels in wild-type mouse astrocytes or those expressing humanized variants of APOE, APOE3, and APOE4. Neuron-directed knockdown of Psn in Drosophila produced apoptosis and cell loss in the brain, phenotypes suppressed by reductions in sfl expression. Abnormalities in mitochondria, liposomes, and autophagosome-derived structures in animals with Psn knockdown were also rescued by reduction of sfl. These findings support the direct involvement of HSPGs in AD pathogenesis.

7.
Nat Commun ; 15(1): 7300, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39181869

RESUMEN

Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (<100 kDa) at near-atomic resolution. This study expands the understanding of SAMs and provides a key to better control the interaction of protein with air-water interface.


Asunto(s)
Aire , Microscopía por Crioelectrón , Grafito , Agua , Microscopía por Crioelectrón/métodos , Agua/química , Grafito/química , Tensoactivos/química , Proteínas/química , Humanos
8.
Arch Insect Biochem Physiol ; 116(4): e22138, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39118528

RESUMEN

To determine the optimal temperature range for the development and reproduction of three spider mites (Eotetranychus sexmaculatus, Eotetranychus orientalis, and Oligonychus biharensis), this study investigated their developmental period, survival rate, lifespan, and reproduction under five temperatures, 21, 24, 27, 30, and 33°C, to predict and control in the field. With the gathered data, a two-sex life table was constructed for each of them. The results revealed that as the temperature increased, both O. biharensis and E. orientalis displayed a gradual reduction in their generation period. Furthermore, an inverse relationship was observed between lifespan and temperature for all three spider mite species. When examining the survival rates at varying temperatures, E. sexmaculatus exhibited the highest rate (98%) at 33°C, while E. orientalis and O. biharensis demonstrated their highest survival rates at 24°C, reaching 90% and 100% respectively. Regarding reproduction, O. biharensis displayed the highest oviposition rates at 30°C with an average of 17.45 eggs per individual. Conversely, E. sexmaculatus and E. orientalis exhibited the highest oviposition rates at 33°C, averaging at 15.22 and 21.38 eggs per individual respectively. Significantly higher intrinsic growth rates were observed for O. biharensis and E. orientalis at 33°C, with rates of 0.22 and 0.26 respectively. In contrast, E. sexmaculatus demonstrated the highest intrinsic growth rate at 27°C. The temperature of 27°C was more suitable for the growth of the E. sexmaculatus, while 33°C was the optimal temperature for the E. orientalis and O. biharensis. The current findings provide valuable guidance for the control and prevention of these three spider mites.


Asunto(s)
Tablas de Vida , Temperatura , Tetranychidae , Animales , Tetranychidae/fisiología , Tetranychidae/crecimiento & desarrollo , Femenino , Masculino , Reproducción , Longevidad , Oviposición , Hevea/crecimiento & desarrollo
9.
J Asian Nat Prod Res ; : 1-7, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39093992

RESUMEN

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

10.
Histochem Cell Biol ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39093409

RESUMEN

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

11.
Heliyon ; 10(15): e34920, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39166081

RESUMEN

Background and aim: Insulin-like growth factor-1 may be involved in the epithelial-to-mesenchymal transition process. It can mitigate adverse effects when interacting with insulin-like growth factor binding protein 3. This study aimed to explore alterations in the expression of these two factors in the colonic tissue of mice with ulcerative colitis. Method: This study utilized animal models. Mice were randomly allocated into three distinct groups. Disease activity index assessment was performed first, followed by histological grading of colitis. Protein and mRNA expression levels were determined using Western blotting and RT-qPCR. Immunohistochemical detection was used to determine histochemistry scores. Pearson correlation and SPSS 25.0 software were used for data analysis. Results: The findings indicated a reduction in the expression of the two investigated factors as well as in epithelial-to-mesenchymal transition epithelial markers during inflammation, while the expression of noninflammatory factors increased. These effects were notably amplified following treatment. Interestingly, the changes in epithelial-to-mesenchymal transition-inducing factors and mesenchymal markers contradicted this trend. Pearson correlation analysis revealed a correlation between molecular indicators of change and epithelial-to-mesenchymal transition. Conclusion: Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 may play a protective role in the development and progression of ulcerative colitis, potentially through their inhibition of the epithelial-to-mesenchymal transition. These factors hold promise as targets for the clinical diagnosis and treatment of ulcerative colitis.

12.
Chem Commun (Camb) ; 60(67): 8840-8843, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39005066

RESUMEN

Au@Ag core-shell composites were successfully fabricated on urchin-like covalent organic frameworks (COFs), providing a platform with numerous hot spots for the detection of two categories of emerging contaminants: sulfonamide antibiotics and nanoplastics, using surface-enhanced Raman spectroscopy (SERS). Au seeds (∼10 nm) were generated on the COFs, leveraging the reducing properties of the vinyl and imino groups within the framework. This ensured the growth of dense and uniformly distributed Ag nanoparticles. The COFs exceptionally large surface area (2324 m2 g-1) and high adsorption capacity, significantly contributed to the enrichment and detection of trace pollutants. As a result, using a portable Raman spectrometer, limits of detection of 0.008 µmol L-1 for sulfamethoxazole and 0.029 mg L-1 for polystyrene nanoplastics were achieved.

13.
Biochem Biophys Res Commun ; 727: 150317, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38959733

RESUMEN

Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases.


Asunto(s)
IMP Deshidrogenasa , Mitocondrias , Osteoclastos , Osteogénesis , Osteoporosis , Ovariectomía , Fosforilación Oxidativa , Animales , Femenino , Ratones , Resorción Ósea/metabolismo , Resorción Ósea/genética , Resorción Ósea/patología , Resorción Ósea/etiología , Diferenciación Celular , IMP Deshidrogenasa/metabolismo , IMP Deshidrogenasa/genética , IMP Deshidrogenasa/deficiencia , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Mitocondrias/patología , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis/metabolismo , Osteoporosis/etiología , Osteoporosis/genética , Osteoporosis/patología
14.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063002

RESUMEN

Arbutin and 6'-O-caffeoylarbutin (CA) from Vaccinium dunalianum Wight are known for their ability to inhibit melanin synthesis. To boost the production of arbutin and CA, precursor feeding with hydroquinone (HQ) was studied in V. dunalianum suspension cells. The effect of HQ on the biosynthesis of arbutin and CA in the suspension cells was investigated using high-performance liquid chromatography (HPLC), and possible molecular mechanisms were analyzed using metabolomics and transcriptomics analyses. HPLC analysis only showed that the addition of HQ significantly enhanced arbutin synthesis in cells, peaking at 15.52 ± 0.28 mg·g-1 after 0.5 mmol·L-1 HQ treatment for 12 h. Subsequently, metabolomics identified 78 differential expression metabolites (DEMs), of which arbutin and CA were significantly up-regulated metabolites. Moreover, transcriptomics found a total of 10,628 differential expression genes (DEGs). The integrated transcriptomics and metabolomics revealed that HQ significantly enhanced the expression of two arbutin synthase (AS) genes (Unigene0063512 and Unigene0063513), boosting arbutin synthesis. Additionally, it is speculated that CA was generated from arbutin and 3,4,5-tricaffeoylquinic acid catalyzed by caffeoyl transferase, with Unigene0044545, Unigene0043539, and Unigene0017356 as potentially associated genes with CA synthesis. These findings indicate that the precursor feeding strategy offers a promising approach for the mass production of arbutin and CA in V. dunalianum suspension cells and provides new insights for CA biosynthesis in V. dunalianum.


Asunto(s)
Arbutina , Perfilación de la Expresión Génica , Hidroquinonas , Metabolómica , Arbutina/farmacología , Arbutina/análogos & derivados , Arbutina/metabolismo , Arbutina/biosíntesis , Hidroquinonas/metabolismo , Metabolómica/métodos , Transcriptoma , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Metaboloma , Cromatografía Líquida de Alta Presión , Células Cultivadas
15.
Nat Mater ; 23(9): 1193-1199, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39080501

RESUMEN

The question of whether all materials can solidify into the glassy form proposed by Turnbull half a century ago remains unsolved. Some of the simplest systems of monatomic metals have not been vitrified, especially the close-packed face-centred cubic metals. Here we report the vitrification of gold, which is notoriously difficult to be vitrified, and several similar close-packed face-centred cubic and hexagonal metals using a method of picosecond pulsed laser ablation in a liquid medium. The vitrification occurs through the rapid cooling during laser ablation and the inhibition of nucleation by the liquid medium. Using this method, a large number of atomic configurations, including glassy configurations, can be generated simultaneously, from which a stable glass state can be sampled. Simulations demonstrate that the favourable stability of monatomic metals stems from the strong topological frustration of icosahedra-like clusters. Our work breaks the limitation of the glass-forming ability of matter, indicating that vitrification is an intrinsic property of matter and providing a strategy for the preparation and design of metallic glasses from an atomic configuration perspective.

16.
Nat Prod Res ; : 1-7, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992980

RESUMEN

Two new aromatic compounds, namely gastupdin A (1), and gastupdin B (2), together with three known compounds, arundin(3), phomosines B (4) and monocillin IV (5), were isolated from the aerial parts of Gastrodia elata Blume. The structures of the new compounds were confirmed through spectral analyses including NMR, HR-ESI-MS, ECD, UV, and IR. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine-induced cell death in Human Neuroblastoma Cells, with curcumin as the positive control, however, the activity of all compounds was weaker than the positive control, showing no significant activity.

18.
J Adv Res ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964734

RESUMEN

INTRODUCTION: Intestinal immune dysregulation is strongly linked to the occurrence and formation of tumors. RING finger protein 128 (RNF128) has been identified to play distinct immunoregulatory functions in innate and adaptive systems. However, the physiological roles of RNF128 in intestinal inflammatory conditions such as colitis and colorectal cancer (CRC) remain controversial. OBJECTIVES: To elucidate the function and mechanism of RNF128 in colitis and CRC. METHODS: Animal models of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced CRC were established in WT and Rnf128-deficient mice and evaluated by histopathology. Co-immunoprecipitation and ubiquitination analyses were employed to investigate the role of RNF128 in IL-6-STAT3 signaling. RESULTS: RNF128 was significantly downregulated in clinical CRC tissues compared with paired peritumoral tissues. Rnf128-deficient mice were hypersusceptible to both colitis induced by DSS and CRC induced by AOM/DSS or APC mutation. Loss of RNF128 promoted the proliferation of CRC cells and STAT3 activation during the early transformative stage of carcinogenesis in vivo and in vitro when stimulated by IL-6. Mechanistically, RNF128 interacted with the IL-6 receptor α subunit (IL-6Rα) and membrane glycoprotein gp130 and mediated their lysosomal degradation in ligase activity-dependent manner. Through a series of point mutations in the IL-6 receptor, we identified that RNF128 promoted K48-linked polyubiquitination of IL-6Rα at K398/K401 and gp130 at K718/K816/K866. Additionally, blocking STAT3 activation effectively eradicated the inflammatory damage of Rnf128-deficient mice during the transformative stage of carcinogenesis. CONCLUSION: RNF128 attenuates colitis and colorectal tumorigenesis by inhibiting IL-6-STAT3 signaling, which sheds novel insights into the modulation of IL-6 receptors and the inflammation-to-cancer transition.

19.
Curr Issues Mol Biol ; 46(7): 6769-6782, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39057046

RESUMEN

Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 15 compounds were identified, including 5 flavonoids (1-5), a galactosylglycerol derivative (6), a terpenoid (7), 4 lignans (8-11), and 4 phenolic acids (12-15). Compounds 6-7 and 9-12 were isolated from the genus Camellia for the first time. The remaining compounds were also isolated from C. fascicularis for the first time. Evaluation of antioxidant and antimicrobial activities revealed that compounds 5 and 8-11 exhibited stronger antioxidant activity than the positive drug ascorbic acid, while compounds 7, 13, and 15 showed similar activity to ascorbic acid. The minimum inhibitory concentration (MIC) of antibacterial activity for compounds 5, 7, 9, 11, and 13 against Pseudomonas aeruginosa was comparable to that of the positive control drug tetracycline at a concentration of 62.50 µg/mL; other secondary metabolites inhibited Escherichia coli and Staphylococcus aureus at concentrations ranging from 125-250 µg/mL.

20.
Foods ; 13(14)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39063349

RESUMEN

Camellia fascicularis has important ornamental, medicinal, and food values, which also have tremendous potential for exploiting bioactivities. We performed the bioactivity-guided (antioxidant and antimicrobial) screening of eight fractions obtained from the ethyl acetate phase of C. fascicularis. The antioxidant activity was measured by DPPH, ABTS, and FRAP, and the antibacterial activity was measured by the minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. The results of bioactivity-guided isolation indicated that the major antioxidant compounds in the ethanolic extracts of C. fascicularis may be present in fractions (Fr.) (A-G, obtained after silica gel column chromatography). Fr. (D-I, obtained after silica gel column chromatography) is a fraction of C. fascicularis with antimicrobial activity. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 17 compounds were identified, including four phenolics (1, 3-4, and 14), a phenylpropane (2), five terpenoids (5-7, 12, and 15), four flavonoids and flavonoid glycosides (8-10 and 16), and two lignins (13 and 17). Compounds 4-7, 13-15, and 17 were isolated from the genus Camellia for first time. The remaining compounds were also isolated from C. fascicularis for first time. The evaluation of antioxidant and antimicrobial activities revealed that compounds 1, 3, 9, 11, and 17 exhibited higher antioxidant activity than the positive control drug (ascorbic acid), and compounds 4, 8, 10, and 13 showed similar activity to ascorbic acid. The other compounds had weaker or no significant antioxidant activities. The MIC of antibacterial activity for compounds 4, 7, and 11-13 against P. aeruginosa was comparable to that of the positive control drug tetracycline at 125 µg/mL, and other secondary metabolites inhibited E. coli and S. aureus at 250-500 µg/mL. This is also the first report of antioxidant and antimicrobial activities of compounds 5-7, 13-15, and 17. The results of the study enriched the variety of secondary metabolites of C. fascicularis and laid the foundation for further research on the pharmacological efficacy and biological activity of this plant.

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