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1.
Anal Chem ; 96(16): 6236-6244, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38446717

RESUMEN

In recent years, the expression and progression of programmed cell death ligand 1 (PD-L1) as an immunomarker in the context of a cell metabolic environment has gained significant attention in cancer research. However, intercellular bioprocesses that control the dynamics of PD-L1 have been largely unexplored. This study aimed to explore the cell metabolic states and conditions that govern dynamic variations of PD-L1 within the cell metabolic environment using an aptamer-based surface-enhanced Raman scattering (SERS) approach. The aptamer-SERS technique offers a sensitive, rapid, and powerful analytical tool for targeted and nondestructive detection of an immunomarker with high sensitivity and specificity. By combining aptamer-SERS with cell state profiling, we investigated the modulation in PD-L1 expression under different metabolic states, including glucose deprivation, metabolic coenzyme activity, and altered time/concentration-based cytokine availability. The most intriguing features in our findings include the cell-specific responses, cell differentiation by revealing distinct patterns, and dynamics of PD-L1 in different cell lines. Additionally, the time-dependent variations in PD-L1 expression, coupled with the dose-dependent relationship between glucose concentration and PD-L1 levels, underscore the complex interplay between immune checkpoint regulation and cellular metabolism. Therefore, this work demonstrates the advantages of using highly-sensitive and specific aptamer-SERS nanotags for investigating the immune checkpoint dynamics and related metabolic bioprocess.

2.
J Bone Miner Metab ; 42(1): 99-114, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38057603

RESUMEN

INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.


Asunto(s)
Fracturas Óseas , Osteoporosis , Humanos , Densidad Ósea , Osteoporosis/epidemiología , Fracturas Óseas/epidemiología , Antebrazo ,
3.
Artículo en Inglés | MEDLINE | ID: mdl-39318248

RESUMEN

Ganoderma lucidum, a popular medicinal fungus, has been utilized to treat a variety of diseases. It possesses a unique therapeutic and pharmacological reputation in suppressing cancer/tumor progression, especially breast cancer, due to its embedded rich bioactive chemical constituents, mainly triterpenoids (ganoderic acids). The most prevalent malignant tumor in women with a high mortality and morbidity rate is breast cancer. Ganoderic acids A, D, DM, F, and H are evidenced in previous research to have breast cancer-preventive properties by exhibiting autophagic and apoptosis, anti-proliferative, and anti-angiogenesis effects. However, the anti-breast cancer mechanism remains unclear. The putative targets of the ganoderic acids were further determined using bioinformatics techniques and molecular docking calculation. Finally, the key targets were verified in vitro. A total of 53 potential target proteins associated with 202 pathways were predicted to be related to breast cancer. The potential targets were narrowed down to six key targets (AKT1, PIK3CA, epidermal growth factor receptor [EGFR], STAT1, ESR1, and CTNNB1), using different algorithms of the CytoHubba plugin, which were further validated using molecular docking analysis. The ganoderic acid DM (GADM) and the targets (PIK3CA and EGFR) with the strongest interactions were validated via MDA-MB-231 and MCF7 cells. The expression level of PIK3CA in both MDA-MB-231 and MCF7 cells was dose-dependently suppressed by GADM, whereas EGFR expression was unexpectedly increased, which warrants further investigation. These data indicated that the network pharmacology-based prediction of GADM targets for treating human breast cancer could be reliable.

4.
Opt Express ; 30(19): 34064-34076, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36242428

RESUMEN

A soft highly sensitive tactile sensor based on an in-fiber interferometer embedded in polydimethylsiloxane (PDMS) structure is studied. Theoretical simulation obtains that the high order sensing modes and PDMS can improve the sensitivity. Experiments show that different order sensing modes, derived by fast Fourier transform (FFT) and inverse FFT methods, present different sensing performance. Corresponding to high order mode, 1.3593 nm/kPa sensitivity and 37 Pa (0.015 N) detection limit is obtained. Meanwhile, it also shows very good stability, reproducibility, and response time. This study not only demonstrates a tactile sensor with high sensitivity but also provides a novel sensing modes analysis method.

5.
Analyst ; 147(22): 5082-5090, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36217766

RESUMEN

Acetylation can be regulated by histone deacetylases (HDACs) and histone acetyltransferases (HATs), and the imbalance between HDACs and HATs can lead to cancers. Trichostatin A (TSA), as one of the typical HDAC inhibitors (HDACis), may regulate the acetylation level and thus prevent the proliferation of cancer cells, in which the metabolic change of glycolysis is involved. However, the dynamic process of glycolysis has not yet been explored, and the mechanism is still elusive. In this work, we constructed GFP-actin-HeLa cells to observe the dynamic change of glycolysis in situ and found that the GFP fluorescence enhanced significantly after TSA treatment, which was consistent with the change of pH in the cells (pHi) depending on the change of lactate originated from glycolysis. Furthermore, we confirmed that the glycolysis was inhibited after TSA treatment, and this process was associated with HIF-1α and c-Myc regulation. As such, this work not only demonstrates the usefulness of the GFP fluorescent probe for monitoring the metabolic process of glycolysis in situ, but also sheds new light on the mechanism of glycolysis suppression in the cancer cells treated with HDACi.


Asunto(s)
Glucólisis , Histona Desacetilasas , Humanos , Acetilación , Fluorescencia , Células HeLa , Histona Desacetilasas/metabolismo
6.
Microb Cell Fact ; 20(1): 115, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34107983

RESUMEN

BACKGROUND: Interleukin-15 (IL-15) is a critical cytokine for the development, proliferation, and function of natural killer (NK) cells, NKT cells, and CD8+ memory T cells and has become one of the most promising protein molecules for the treatment of cancer and viral diseases. However, there are several limitations in applying IL-15 in therapy, such as its low yield in vitro, limited potency, and short half-life in vivo. To date, there are several recombinant IL-15 agonists based on configurational modifications that are being pursued in the treatment of cancer, such as ALT-803, which are mainly produced from mammalian cells. RESULTS: In this study, we designed two different forms of the IL-15 complex, which were formed by the noncovalent assembly of IL-15 with dimeric or monomeric sushi domain of IL-15 receptor α (SuIL-15Rα)-IgG4 Fc fusion protein and designated IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc, respectively. The two IL-15 complexes were expressed in Pichia pastoris (P. pastoris), and their activities and half-lives were evaluated and compared. Pharmacokinetic analysis showed that IL-15/SuIL-15Rα-dFc had a half-life of 14.26 h while IL-15/SuIL-15Rα-mFc had a half-life of 9.16 h in mice, which were much longer than the 0.7-h half-life of commercial recombinant human IL-15 (rhIL-15). Treatment of mice with intravenous injection of the two IL-15 complexes resulted in significant increases in NK cells, NKT cells, and memory CD8+ T cells, which were not observed after rhIL-15 treatment. Treatment of human peripheral blood mononuclear cells (PBMCs) from healthy donors with the two IL-15 complexes yielded enhanced NK and CD8+ T cell activation and proliferation, which was comparable to the effect of rhIL-15. CONCLUSIONS: These findings indicate that the IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc produced in P. pastoris exhibit potent activities and prolonged half-lives and may serve as superagonists for immunotherapy in further research and applications.


Asunto(s)
Fragmentos Fc de Inmunoglobulinas/metabolismo , Subunidad alfa del Receptor de Interleucina-15/metabolismo , Interleucina-15/agonistas , Interleucina-15/metabolismo , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/metabolismo , Saccharomycetales/metabolismo , Animales , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Fermentación , Semivida , Humanos , Fragmentos Fc de Inmunoglobulinas/genética , Fragmentos Fc de Inmunoglobulinas/inmunología , Interleucina-15/genética , Interleucina-15/inmunología , Subunidad alfa del Receptor de Interleucina-15/genética , Subunidad alfa del Receptor de Interleucina-15/inmunología , Células Asesinas Naturales/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Células T Asesinas Naturales/inmunología , Conformación Proteica , Dominios Proteicos , Organismos Libres de Patógenos Específicos
7.
Plant Mol Biol ; 104(3): 235-248, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32757127

RESUMEN

KEY MESSAGE: Two PaGL1-like genes were identified in London plane and functional in Arabidopsis, moreover, may play an important role in the regulation of trichome development in London plane. Trichome development is governed by a complex regulatory network. In Arabidopsis, subgroup 15 of the R2R3 MYB transcription factor family, which includes GLABRA1 (GL1), is involved in trichome development. In this study, we isolated and characterized two PaGL1-like genes from London plane (Platanus acerifolia). Sequence alignment and phylogenetic analysis indicated that these PaGL1-like genes are homologous to AtGL1. Quantitative real-time PCR (qRT-PCR) analysis showed that PaGL1-like1 was expressed in all of the tested organs taken from adult London plane trees, including trichomes, petioles after trichome removal, stems after trichome removal, and leaves after trichome removal, and also in the roots, cotyledons, hypocotyls and true leaves of seedlings. By contrast, the PaGL1-like2 was expressed only in the trichomes and leaves after trichome removal from adult trees, and in the cotyledons and true leaves of seedlings. Overexpression of PaGL1-like genes caused trichome abortion when transferred into wild type Arabidopsis and promoted trichome formation in the gl1 mutant. The expression profiles of some trichome-related genes were changed in transgenic Arabidopsis lines, and yeast two-hybrid analysis indicated that PaGL1-like proteins can directly interact with trichome-related bHLH proteins from both P. acerifolia and Arabidopsis. These results suggest that PaGL1-like genes are functional in Arabidopsis and may play an important role in the regulation of trichome development in London plane.


Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tracheophyta/genética , Tricomas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Regulación de la Expresión Génica de las Plantas , Proteínas de Homeodominio/genética , Filogenia , Hojas de la Planta/genética , Plantas Modificadas Genéticamente , Alineación de Secuencia , Tracheophyta/metabolismo , Factores de Transcripción/genética , Transcriptoma , Tricomas/crecimiento & desarrollo
8.
Anal Chem ; 92(21): 14452-14458, 2020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33085464

RESUMEN

The SWI/SNF complex is a highly conserved chromatin remodeling complex and can hydrolyze ATP by its catalytic subunit BRG1 or BRM to reconstruct the chromatin. To investigate whether this ATP-dependent chromatin remodeling could affect the DNA conformation, we therefore regulated (knocked down or overexpressed) BRG1/BRM in the cells and applied Fourier transform infrared (FTIR) spectroscopy to probe DNA conformational changes. As a result, we found that BRG1/BRM was indeed associated with the DNA conformational changes, in which knockdown of BRG1/BRM reduced Z-DNA conformation, while overexpression of BRG1/BRM enhanced Z-DNA conformation. This Z-DNA conformational transformation was also verified using the Z-DNA-binding proteins. Therefore, this work has provided a direct analytical tool to probe Z-DNA transformation upon ATP-dependent chromatin remodeling.


Asunto(s)
Ensamble y Desensamble de Cromatina , ADN de Forma Z/química , Conformación de Ácido Nucleico , Espectroscopía Infrarroja por Transformada de Fourier , Adenosina Trifosfato/metabolismo , Línea Celular Tumoral , ADN Helicasas/deficiencia , ADN Helicasas/genética , ADN de Forma Z/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Factores de Transcripción/deficiencia , Factores de Transcripción/genética
9.
BMC Biotechnol ; 19(1): 54, 2019 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-31362722

RESUMEN

BACKGROUND: The microbial transglutaminase (MTG) is inactive when only the mature sequence is expressed in Pichia pastoris. Although co-expression of MTG and its N-terminal pro-peptide can obtain the active MTG, the enzyme activity was still low. One of the basic steps for strain improvement is to ensure a sufficient level of transcription of the heterologous gene, based on promoter strength and gene copy number. To date, high-copy-number recombinants of P. pastoris are achievable only by cloning of gene concatemers, so methods for rapid and reliable multicopy strains are therefore desirable. RESULTS: The coexpression strains harboring different copies mtg were obtained successfully by stepwise increasing Zeocin concentration based on the rDNA sequence of P. pastoris. The genome of coexpression strains with the highest enzyme activity was analyzed by real-time fluorescence quantitative PCR, and three copies of mtg gene (mtg-3c) was calculated according to the standard curve of gap and mtg genes (gap is regarded as the single-copy reference gene). The maximum enzyme activity of mtg-3c was up to 1.41 U/mL after being inducted for 72 h in 1 L flask under optimal culture conditions, and two protein bands were observed at the expected molecular weights (40 kDa and 5 kDa) by Western blot. Furthermore, among the strains detected, compared with mtg-2c, mtg-6c or mtg-8c, mtg-3c is the highest expression level and enzyme activity, implying that mtg-3c is the most suitable for co-expression pro-peptide and MTG. CONCLUSIONS: This study provides an effective strategy for improving the expression level of active MTG by directional increasing of mtg copies in P. pastoris.


Asunto(s)
Proteínas Fúngicas/genética , Dosificación de Gen , Regulación Enzimológica de la Expresión Génica , Regulación Fúngica de la Expresión Génica , Pichia/genética , Transglutaminasas/genética , Clonación Molecular/métodos , Proteínas Fúngicas/metabolismo , Genoma Fúngico/genética , Pichia/enzimología , Regiones Promotoras Genéticas/genética , Transglutaminasas/metabolismo
10.
Planta ; 249(3): 861-877, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30448862

RESUMEN

MAIN CONCLUSION: Four R3 MYB genes were cloned and identified from Platanus acerifolia and analysed according to endogenous gene expression profiles, protein-protein interaction patterns, phenotypic effects and related gene expression profiles in transgenic Arabidopsis, suggesting that London plane R3 MYB genes inhibit trichome formation in Arabidopsis. The CPC-like MYB transcription factors including CAPRICE (CPC), TRIPTYCHON (TRY), ENHANCER OF TRY AND CPC 1, 2 and 3 (ETC1, ETC2 and ETC3), TRICHOMELESS1 (TCL1) and TRICHOMELESS2(TCL2) play important roles in controlling trichome patterning in Arabidopsis. In this study, four sequences homologous with the Arabidopsis CPC family were identified from London plane and named PaTRY, PaCPC-like1, PaCPC-like2 and PaCPC-like3. Over-expression of PaTRY, PaCPC-like1, PaCPC-like2 and PaCPC-like3 in Arabidopsis resulted in glabrous phenotypes. In addition, expression of endogenous GL2, GL1, MYB23, TTG2 and a set of R3 MYB-encoding genes was markedly reduced. Furthermore, the protein products of PaTRY, PaCPC-like1, PaCPC-like2 and PaCPC-like3 were shown to interact with PaGL3 in yeast two-hybrid assays. Together, these results likely suggest that the mechanisms of trichome regulation in London plane have similarities with those in Arabidopsis.


Asunto(s)
Genes de Plantas/fisiología , Genes myb/fisiología , Magnoliopsida/genética , Proteínas de Plantas/fisiología , Factores de Transcripción/fisiología , Tricomas/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Clonación Molecular , Genes de Plantas/genética , Genes myb/genética , Microscopía Electrónica de Rastreo , Mutagénesis Sitio-Dirigida , Filogenia , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/ultraestructura , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Reacción en Cadena en Tiempo Real de la Polimerasa , Alineación de Secuencia , Factores de Transcripción/genética , Transcriptoma , Tricomas/genética , Tricomas/ultraestructura , Técnicas del Sistema de Dos Híbridos
11.
Biochem Biophys Res Commun ; 490(1): 22-28, 2017 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-28576493

RESUMEN

Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-ß mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-ß activation was ascribed to 3Cpro of RV-C, and the 40-His site of 3Cpro played an important role. Furthermore, RIG-I was degraded by 3Cpro in a caspase-dependent manner and 3Cpro cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells.


Asunto(s)
Tolerancia Inmunológica , Inmunidad Innata/inmunología , Rhinovirus/inmunología , Células HEK293 , Células HeLa , Humanos , Interferón Tipo I/inmunología
12.
Microb Cell Fact ; 15(1): 209, 2016 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-27927205

RESUMEN

BACKGROUND: Interferon (IFN)-α has been commonly used as an antiviral drug worldwide; however, its short half-life in circulation due to its low molecular weight and sensitivity to proteases impacts its efficacy and patient compliance. RESULTS: In this study, we present an IgG1 Fc fusion strategy to improve the circulation half-life of IFN-α. Three different forms of IgG1 Fc fragments, including the wild type, aglycosylated homodimer and aglycosylated single chain, were each fused with IFN-α and designated as IFN-α/Fc-WT, IFN-α/Fc-MD, and IFN-α/Fc-SC, respectively. The recombinant proteins were expressed in Pichia pastoris and tested using antiviral and pharmacokinetic assays in comparison with the commercial pegylated-IFN-α (PEG-IFN-α). The in vitro study demonstrated that IFN-α/Fc-SC has the highest antiviral activity, while IFN-α/Fc-WT and IFN-α/Fc-MD exhibited antiviral activities comparable to that of PEG-IFN-α. The in vivo pharmacokinetic assay showed that both IFN-α/Fc-WT and IFN-α/Fc-MD have a longer half-life than PEG-IFN-α in SD rats, but IFN-α/Fc-SC has the shortest half-life among them. Importantly, the circulating half-life of 68.3 h for IFN-α/Fc-MD was significantly longer than those of 38.2 h for IFN-α/Fc-WT and 22.2 h for PEG-IFN-α. CONCLUSIONS: The results demonstrate that the elimination of N-glycosylation by mutation of putative N-glycosylation site further prolongs the half-life of the IFN-α/Fc fusion protein and could present an alternative strategy for extending the half-life of low-molecular-weight proteins expressed by P. pastoris for in vivo studies as well as for future clinical applications.


Asunto(s)
Fragmentos Fc de Inmunoglobulinas/metabolismo , Interferón-alfa/farmacocinética , Mutación , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes de Fusión/farmacocinética , Animales , Glicosilación , Fragmentos Fc de Inmunoglobulinas/genética , Interferón-alfa/genética , Interferón-alfa/metabolismo , Ratas , Proteínas Recombinantes de Fusión/genética
13.
Photochem Photobiol ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695248

RESUMEN

Astaxanthin (AST) is a xanthophyll carotenoid with strong oxidation resistance, which can effectively scavenge various free radicals and protect organisms from oxidative damage. AST is also known to have prominent anti-aging effects, but the underlying mechanism of AST in anti-radiation aging is largely unknown. In this work, we applied ultraviolet (UV) irradiation to accelerate the aging of Caenorhabditis elegans (C. elegans) and treated the nematodes with AST to explore whether and how AST could attenuate the radiation-induced aging effect. Our results showed that AST improved the survival rate of C. elegans, reduced the aging biomarkers, and alleviated the mitochondrial dysfunction caused by the irradiation. Based on the transcriptome sequencing analysis, we identified that the key genes regulated by AST were involved in JNK-MAPK and DAF-16 longevity signaling pathways. Furthermore, we employed jnk-1 and daf-16 mutants and verified the role of the JNK-1/DAF-16 signaling pathway in the anti-aging effect. As such, this study has not only demonstrated that AST can resist the aging process caused by UV-irradiation but also revealed the anti-aging mechanism of AST through JNK-1/DAF-16 activation in C. elegans.

14.
Food Funct ; 15(8): 4207-4222, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38512055

RESUMEN

Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and the modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharides (LPS) served as inflammatory stimuli. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPSs escalated the expression of inflammation-related molecules. Our results demonstrate that AST intervention could effectively alleviate LPS-induced oxidative stress, facilitate cellular repair, and significantly attenuate inflammation. Further exploration of the anti-inflammatory mechanism revealed AST could substantially inhibit NF-κB translocation and activation, and mitigate inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as a popular dietary supplement of anti-inflammatory or immunomodulatory function.


Asunto(s)
Antiinflamatorios , Inflamación , Interleucina-6 , Lipopolisacáridos , Macrófagos , FN-kappa B , Xantófilas , Xantófilas/farmacología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Antiinflamatorios/farmacología , FN-kappa B/metabolismo , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Células THP-1 , Simulación del Acoplamiento Molecular , Antioxidantes/farmacología
15.
RSC Adv ; 14(39): 28569-28584, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39247503

RESUMEN

Human glucose transporters (GLUTs) facilitate the uptake of hexoses into cells. In cancer, the increased proliferation necessitates higher expression of GLUTs, with particular emphasis on GLUT1 and GLUT3. Thus, inhibiting GLUTs holds promise as an anticancer therapy by starving these cells of fuel. Ganoderic acid A (GAA), a triterpene found in Ganoderma lucidum, has anticancer and antidiabetic properties. Recent studies show that GAA reduces glucose uptake in cancer cells, which indicates that GAA may affect GLUT1/GLUT3 by inhibiting glucose uptake. Therefore, this study aimed to inspect whether GAA could target GLUT1/GLUT3 and play an inhibitory role in changing their endofacial and exofacial conformations. To this end, AlphaFold2 was employed to model the endofacial and exofacial conformations of GLUT3 and GLUT1, respectively. Molecular docking, molecular dynamics simulation, cell viability, cellular thermal shift assays (CETSA), glucose uptake, qPCR, and western blotting were harnessed. In comparison to the endofacial (cytochalasin B) and exofacial (phloretin) GLUT1/3 inhibitors, the computational findings unveiled GAA's capacity to bind and stabilize GLUT1/3 in their two conformational states, with a preference for binding the endofacial conformation. A low, non-cytotoxic dose of GAA thermally stabilized both transporters and inhibited glucose uptake in human lung cancer cells, similar to cytochalasin B and phloretin. In conclusion, this study has unearthed novel functionalities of GAA, suggesting its potential utility in cancer therapy by targeting glucose metabolism.

16.
J Hazard Mater ; 452: 131306, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37004443

RESUMEN

The extensive abuse and inadvertent discharge of various antibiotics into the environment has become a serious problem for posing a big threat to human health. In order to deal with this problem, we utilized cold atmospheric plasma jet (CAPJ) to treat two different antibiotics, namely, norfloxacin and chloramphenicol, and investigated the efficiencies and corresponding mechanisms for removing the mixed antibiotics. In the application of the CAPJ technique, we made use of not only the direct plasma processing, but also the indirect plasma-activated water (PAW) treatment. The efficiency for mixed antibiotics treatment was considerably enhanced as compared to the efficiency for treatment of single antibiotics. The contributions from the CAPJ-induced reactive oxygen/nitrogen species (RONS) were examined, showing that ·OH and 1O2 played a major role in the degradation of norfloxacin and chloramphenicol in the direct plasma treatment, while 1O2 played a major role in the PAW treatment. The bio-toxicity evaluation was also provided to verify the ecological safety of the CAPJ treatment. As such, this work has not only showed the effectiveness of CAPJ treatment of mixed antibiotics, but also elucidated the mechanisms for the enhanced treatment efficiency, which may provide a new solution for treatment of antibiotics in the environment.


Asunto(s)
Norfloxacino , Gases em Plasma , Humanos , Norfloxacino/toxicidad , Cloranfenicol/toxicidad , Gases em Plasma/farmacología , Agua , Antibacterianos/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo/metabolismo
17.
Food Res Int ; 172: 113161, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37689913

RESUMEN

Owing to the recognized therapeutic characteristics of G. lucidum, it is one of the most extensively researched mushrooms as a chemopreventive agent and as a functional food. It is a known wood-degrading basidiomycete possessing numerous pharmacological functions and is termed a natural pharmacy store due to its rich number of active compounds which have proved to portray numerous therapeutic properties. This current review highlights studies on the potentialities of G. lucidum extracts as functional ingredients on organoleptic and nutritional properties of food products (e.g., dairy, wine, beverage, bakery, meat, and other products). In addition, the study delved into various aspects of encapsulated G. lucidum extracts, their morphological and rheological characteristics, prebiotic and immunomodulatory importance, the effects on apoptosis, autophagy, cancer therapy, inflammatory responses, oxidative stress, antioxidant activities, and safety concerns. These findings have significant implications for the development of new products in the food and pharmaceutical industries. On the other hand, the various active compounds extracted from G. lucidum exhibited no toxic or adverse effects, and the appeal for it as a dietary food, natural remedy, and health-fortifying food is drastically increasing as well as attracting the interest of both the industrial and scientific communities. Furthermore, the formation of functional foods based on G. lucidum appears to have actual promise and exciting prospects in nutrition, food, and pharmaceutical sciences.


Asunto(s)
Reishi , Bebidas , Alimentos Funcionales , Carne , Estado Nutricional , Vehículos Farmacéuticos
18.
Mol Biotechnol ; 65(4): 645-654, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36155889

RESUMEN

Leucoanthocyanidin reductase (LAR) is the critical enzyme in the synthesis pathway of proanthocyanidins, which are the primary pigments in brown cotton fibers. Our previous study has revealed significant differences in the expression levels of GhLAR1 between white and brown cotton fibers at 10 DPA. In this work, the expression pattern of the GhLAR1 gene was further studied, and the promoter of GhLAR1 (1780 bp) was isolated and characterized. Bioinformatic analysis indicated that GhLAR1 promoter contained many known light response elements and several defenses related to transcriptional factor-binding boxes, which may partially explain the response of the GhLAR1 to temperature, NaCl, and PEG treatments. Furthermore, GhLAR1 was preferentially and strongly expressed in fibers and flowers of cotton, and the expression levels in all tested tissues (especially fibers) of brown cotton were significantly higher than those in white cotton. Consistent with the expression analysis, the GhLAR1 promoter mainly drove GUS expression in epidermal trichomes and floral organs.


Asunto(s)
Antocianinas , Gossypium , Gossypium/genética , Antocianinas/genética , Antocianinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fibra de Algodón , Oxidorreductasas/genética , Oxidorreductasas/metabolismo
19.
PLoS One ; 17(8): e0273351, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36006983

RESUMEN

OBJECTIVE: The purpose of this study was to analyse the biomechanical characteristics of pedicle screws with different placement methods and diameters in the treatment of Tile C1 pelvic fractures by finite element simulation technology and to compare them with the plate fixation model to verify the effectiveness of pedicle screw fixation. METHODS: A three-dimensional digital model of a normal pelvis was obtained using computed tomography images. A finite element model of a normal pelvis containing major ligaments was built and validated (Model 1). Based on the verified normal pelvis finite element model, a Tile C1 pelvic fracture model was established (Model 2), and then a plate fixation model (Model 3) and a pedicle screw fixation model with different screw placement methods and diameters were established (Models 4-15). For all pelvic fracture fixation models, a vertical load of 500 N was applied on the upper surface of the sacrum to test the displacement and stress distribution of the pelvis in the standing state with both legs. RESULTS: The finite element simulation results showed the maximum displacement of Model 1 and Models 3-15 to be less than 1 mm. The overall maximum displacement of Models 4-15 was slightly larger than that of Model 3 (the maximum difference was 177.91×10-3 mm), but the maximum displacement of iliac bone and internal fixation in Models 4-15 was smaller than that of Model 3. The overall maximum stress (maximum stress of the ilium) and maximum stress of internal fixation in Models 4-15 were less than those in Model 3. The maximum displacement difference and maximum stress difference at the fracture of the pubic ramus between each fixed model were less than 0.01 mm and 1 MPa, respectively. The greater the diameter and number of pedicle screws were, the smaller the maximum displacement and stress of the pelvic fracture models were.The maximum displacement and stress of the pelvic fracture models of the screws placed on the injured side of the pubic region were smaller than the screws on the healthy side. CONCLUSION: Both the anterior and posterior pelvic rings are fixed with a pedicle screw rod system for treatment of Tile C1 pelvic fractures, which can obtain sufficient biomechanical stability and can be used as a suitable alternative to other implants.The greater the diameter and number of pedicle screws were, the greater the pelvic stability was, and the greater was the stability of the screws placed on the injured side of the pubic region than the screws on the healthy side.


Asunto(s)
Fracturas Óseas , Tornillos Pediculares , Huesos Pélvicos , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Humanos , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/cirugía , Pelvis/diagnóstico por imagen , Pelvis/cirugía , Sacro/cirugía
20.
Sci Total Environ ; 838(Pt 4): 156576, 2022 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-35688233

RESUMEN

Cold atmospheric plasma (CAP) possesses the ability of high-efficiency disinfection. It is reported that mixtures of reactive oxygen species (ROS) including ·OH, 1O2, O2- and H2O2 generated from CAP have better antimicrobial ability than mimicked solution of mixture of single ROS type, but the reason is not clear. In this study, CAP was applied to treat yeasts in water in order to investigate the fungal inactivation efficiency and mechanism. The results showed that plasma treatment for 5 min could result in >2-log reduction of yeast cells, and application of varied ROS scavengers could significantly increase the yeast survival rate, indicating that ·OH and 1O2 played the pivotal role in yeast inactivation. Moreover, the synergistic effect of 1O2 with other plasma-generated ROS was revealed. 1O2 could diffuse into cells and induce the depolarization of mitochondrial membrane potential (MMP), and different levels of MMP depolarization determined different cell death modes. Mild damage of mitochondria during short-term plasma treatment could lead to apoptosis. For long-term plasma treatment, the cell membrane could be severely damaged by the plasma-generated ·OH, so a large amount of 1O2 could induce more depolarization of MMP, leading to increase of intracellular O2- and Fe2+ which subsequently caused cell inactivation. 1O2 could also induce protein aggregation and increase of RIP1/RIP3 necrosome, leading to necroptosis. With participation of 1O2, endogenous ·OH could also be generated via Fenton and Haber-Weiss reactions during plasma treatment, which potentiated necroptosis. Adding l-His could mitigate membrane damage, inhibit the drop of MMP and the formation of necrosome, and thus prevent the happening of necroptosis. These findings may deepen the understanding of plasma sterilization mechanisms and provide guidance for microbial killing in the environment.


Asunto(s)
Gases em Plasma , Oxígeno Singlete , Desinfección/métodos , Peróxido de Hidrógeno , Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae , Agua
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