Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Genomics ; 116(3): 110831, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38513875

RESUMEN

Hepatitis B virus (HBV) infection is a major etiology of hepatocellular carcinoma (HCC). An interesting question is how different are the molecular and phenotypic profiles between HBV-infected (HBV+) and non-HBV-infected (HBV-) HCCs? Based on the publicly available multi-omics data for HCC, including bulk and single-cell data, and the data we collected and sequenced, we performed a comprehensive comparison of molecular and phenotypic features between HBV+ and HBV- HCCs. Our analysis showed that compared to HBV- HCCs, HBV+ HCCs had significantly better clinical outcomes, higher degree of genomic instability, higher enrichment of DNA repair and immune-related pathways, lower enrichment of stromal and oncogenic signaling pathways, and better response to immunotherapy. Furthermore, in vitro experiments confirmed that HBV+ HCCs had higher immunity, PD-L1 expression and activation of DNA damage response pathways. This study may provide insights into the profiles of HBV+ and HBV- HCCs, and guide rational therapeutic interventions for HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Virus de la Hepatitis B , Neoplasias Hepáticas , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/genética , Humanos , Virus de la Hepatitis B/genética , Fenotipo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Hepatitis B/virología , Hepatitis B/complicaciones , Hepatitis B/genética , Inestabilidad Genómica , Reparación del ADN , Multiómica
2.
Biomacromolecules ; 25(3): 1682-1695, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38417021

RESUMEN

We present a multiscale molecular dynamics (MD) simulation study on self-assembly in methylcellulose (MC) aqueous solutions. First, using MD simulations with a new coarse-grained (CG) model of MC chains in implicit water, we establish how the MC chains self-assemble to form fibrils and fibrillar networks and elucidate the MC chains' packing within the assembled fibrils. The CG model for MC is extended from a previously developed model for unsubstituted cellulose and captures the directionality of H-bonding interactions between the -OH groups. The choice and placement of the CG beads within each monomer facilitates explicit modeling of the exact degree and position of methoxy substitutions in the monomers along the MC chain. CG MD simulations show that with increasing hydrophobic effect and/or increasing H-bonding strength, the commercial MC chains (with degree of methoxy substitution, DS, ∼1.8) assemble from a random dispersed configuration into fibrils. The assembled fibrils exhibit consistent fibril diameters regardless of the molecular weight and concentration of MC chains, in agreement with past experiments. Most MC chains' axes are aligned with the fibril axis, and some MC chains exhibit twisted conformations in the fibril. To understand the molecular driving force for the twist, we conduct atomistic simulations of MC chains preassembled in fibrils (without any chain twists) in explicit water at 300 and 348 K. These atomistic simulations also show that at DS = 1.8, MC chains adopt twisted conformations, with these twists being more prominent at higher temperatures, likely as a result of shielding of hydrophobic methyl groups from water. For MC chains with varying DS, at 348 K, atomistic simulations show a nonmonotonic effect of DS on water-monomer contacts. For 0.0 < DS < 0.6, the MC monomers have more water contacts than at DS = 0.0 or DS > 0.6, suggesting that with few methoxy substitutions, the MC chains are effectively hydrophilic, letting the water molecules diffuse into the fibril to participate in H-bonds with the MC chains' remaining -OH groups. At DS > 0.6, the MC monomers become increasingly hydrophobic, as seen by decreasing water contacts around each monomer. We conclude based on the atomistic observations that MC chains with lower degrees of substitutions (DS ≤ 0.6) should exhibit solubility in water over broader temperature ranges than DS ∼ 1.8 chains.


Asunto(s)
Metilcelulosa , Simulación de Dinámica Molecular , Metilcelulosa/química , Agua/química , Celulosa
3.
Fish Shellfish Immunol ; 150: 109569, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38641216

RESUMEN

Phlorotannins are phenolic compounds with diverse biological activities, yet their efficacy in aquatic animals currently remains unclear. This investigation scrutinized the influence of phlorotannins on the growth, immunity, antioxidant capacity, and intestinal microbiota in Litopenaeus vannamei, concurrently evaluating the potential adverse effects of phlorotannins on L. vannamei. A base diet without phlorotannins supplementation was used as a control, and 4 groups of diets with different concentrations (0, 0.5, 1.0, 2.0 g kg-1) of phlorotannins were formulated and fed to juvenile shrimp (0.25 ± 0.01 g) for 60 days followed by a 24-h challenge with Vibrio parahaemolyticus with triplicate in each group. Compared with the control, dietary 2.0 g kg-1 phlorotannins significantly improved the growth of the shrimp. The activities of enzymes related to cellular immunity, humoral immunity, and antioxidants, along with a notable upregulation in the expression of related genes, significantly increased. After V. parahaemolyticus challenge, the cumulative survival rates of the shrimp demonstrated a positive correlation with elevated concentrations of phlorotannins. In addition, the abundance of Bacteroidetes and functional genes associated with metabolism increased in phlorotannins supplementation groups. Phlorotannins did not elicit any detrimental effects on the biological macromolecules or histological integrity of the hepatopancreas or intestines. Simultaneously, it led to a significant reduction in malondialdehyde content. All results indicated that phlorotannins at concentrations of 2.0 g kg-1 can be used as safe feed additives to promote the growth, stimulate the immune response, improve the antioxidant capacity and intestinal health of L. vannamei, and an protect shrimp from damage caused by oxidative stress.


Asunto(s)
Alimentación Animal , Dieta , Suplementos Dietéticos , Microbioma Gastrointestinal , Penaeidae , Taninos , Vibrio parahaemolyticus , Animales , Penaeidae/inmunología , Penaeidae/crecimiento & desarrollo , Penaeidae/efectos de los fármacos , Penaeidae/microbiología , Alimentación Animal/análisis , Dieta/veterinaria , Microbioma Gastrointestinal/efectos de los fármacos , Taninos/farmacología , Taninos/administración & dosificación , Vibrio parahaemolyticus/fisiología , Suplementos Dietéticos/análisis , Relación Dosis-Respuesta a Droga , Distribución Aleatoria , Inmunidad Innata/efectos de los fármacos
4.
Ecotoxicol Environ Saf ; 269: 115814, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38100851

RESUMEN

Microplastics are detrimental to the environment. However, the combined effects of microplastics and arsenic (As) remain unclear. In this study, we investigated the combined effects of polystyrene (PS) microplastics and As on HepG2 cells. The results showed that PS microplastics 20, 50, 200, and 500 nm in size were taken up by HepG2 cells, causing a decrease in cellular mitochondrial membrane potential. The results of lactate dehydrogenase release and flow cytometry showed that PS microplastics, especially those of 50 nm, enhanced As-induced apoptosis. In addition, transcriptome analysis revealed that TP53, AKT1, CASP3, ACTB, BCL2L1, CASP8, XIAP, MCL1, NFKBIA, and CASP7 were the top 10 hub genes for PS that enhanced the role of As in HepG2 cell apoptosis. Our results suggest that nano-PS enhances As-induced apoptosis. Furthermore, this study is important for a better understanding of the role of microplastics in As-induced hepatotoxicity.


Asunto(s)
Arsénico , Humanos , Arsénico/toxicidad , Células Hep G2 , Microplásticos/toxicidad , Plásticos , Poliestirenos/toxicidad , Apoptosis
5.
Cancer Immunol Immunother ; 72(8): 2741-2755, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37119260

RESUMEN

Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4+ epitope recognition can lead to the lack of greatly limit the persistence of the CD8+ T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+ T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+ T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Humanos , Epítopos de Linfocito T , Nitratos , Antígenos de Neoplasias , Neoplasias/tratamiento farmacológico , Linfocitos T Colaboradores-Inductores , Adyuvantes Inmunológicos , ADN , Inmunoterapia
6.
Ecotoxicol Environ Saf ; 249: 114375, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36508836

RESUMEN

Microplastics (MPs) are widespread in the environment and can be ingested through food, water, and air, posing a threat to human health. In addition, MPs can have a potential combined effect with other toxic compounds. Polystyrene (PS) has been shown to enhance the cytotoxicity of okadaic acid (OA). However, it remains unclear whether this enhancement effect is related to the size of PS particles. In this study, we investigated the mechanism of the combined effect of PS microplastics (PS-MPs) or PS nanoplastics (PS-NPs) and OA on Caco-2 cells. The results indicated that PS-NPs enhanced the cytotoxicity of OA and induced endoplasmic reticulum (ER) stress-mediated apoptosis in Caco-2 cells, compared to PS-MPs. Specifically, PS-NPs and OA cause more severe oxidative stress, lactate dehydrogenase (LDH) release, and mitochondrial membrane depolarization. Furthermore, it induced intracellular calcium overload through store-operated channels (SOCs) and activated the PERK/ATF-4/CHOP pathway to cause ER stress. ER stress promoted mitochondrial damage and finally activated the caspase family to induce apoptosis. This study provided an indirect basis for the assessment of the combined toxicity of MPs or NPs with OA.


Asunto(s)
Apoptosis , Microplásticos , Ácido Ocadaico , Poliestirenos , Contaminantes Químicos del Agua , Humanos , Apoptosis/efectos de los fármacos , Células CACO-2 , Microplásticos/toxicidad , Ácido Ocadaico/toxicidad , Plásticos , Poliestirenos/toxicidad , Contaminantes Químicos del Agua/toxicidad
7.
Biochem Biophys Res Commun ; 634: 10-19, 2022 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-36228540

RESUMEN

Extracellular vesicles (EVs) and their exosome subsets are vesicle-like nanoparticles (EVs) that are secreted by cells and contain various factors that treat various diseases. However, studies on extracting EVs from marine shellfish are still relatively lacking. In this study, EVs were isolated from Pinctada martensii mucus and the efficacy of EVs in modulating the inflammatory environment was demonstrated. A human skin inflammatory cell model was established to investigate the effect of Pinctada martensii mucus-derived EVs on inflammation. The results showed that EVs could restore the viability of inflammatory HaCaT cells and decrease the level of reactive oxygen species (ROS), as well as the mRNA expression of IL-6, IL-8 and TNF-α. The inflammation of HaCaT cells was treated by inhibiting the activation of the MAPK, NF-κB and NLRP3 inflammasome signaling pathways, which prevented the phosphorylation of related inflammatory proteins and the entry of P65 protein into the nucleus. This study provides novel EVs from marine shellfish-derived bioactive materials.


Asunto(s)
Dermatitis , Vesículas Extracelulares , Pinctada , Animales , Humanos , Vesículas Extracelulares/metabolismo , Inflamasomas/metabolismo , Inflamación , Moco/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pinctada/metabolismo , Proteínas Quinasas Activadas por Mitógenos
8.
Inorg Chem ; 61(5): 2490-2498, 2022 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-35067051

RESUMEN

Metal-organic frameworks (MOFs) as friction nanopower generation materials have attracted more and more research and attention because of the inherent three-dimensional framework structure and large aperture. In this work, the ZUT-75(Mn) with a one-dimensional pore structure was synthesized by using electron-rich benzimidazole carboxylic acid ligands, and isomorphic offspring MOF materials were obtained by single crystal-single crystal solvent-assisted metal-ion exchange. The exchange process was monitored by liquid UV-vis spectroscopy, atomic absorption spectrometry, and energy-dispersive X-ray spectroscopy. The metal-oxygen coordination energy, X-ray photoelectron spectroscopy binding energy, and hard-soft acid-base principle verified the spontaneity of the central-metal-exchange reaction. The four materials were applied to a triboelectric nanogenerator (TENG), and the output performance law of ZUT-75 was Co-MT > Zn-MT > Cu-MT > Mn-MT. Among them, the charge and power densities of Co-MT were up to 127.05 µC m-2 and 3280.50 mW m-2. When the density functional theory calculation and variable-temperature magnetic susceptibility test results were combined, it was concluded that low metal-ion-coupling degree promoted the formation and transfer of contact electrifications, which greatly improved the output performance of the TENG. This work provided a new idea for improving the output performance of the TENG.

9.
Cancer Cell Int ; 21(1): 185, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789676

RESUMEN

BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC. METHODS: Exosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples. RESULTS: Western blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes. CONCLUSIONS: We identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC.

10.
BMC Cancer ; 21(1): 519, 2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-33962583

RESUMEN

BACKGROUND: To explore the combined predictive value of serum uric acid (SUA) and tumor response to induction chemotherapy (IC) in locally advanced nasopharyngeal carcinoma (LANPC) patients receiving IC followed by concurrent chemoradiation therapy (CCRT). METHODS: A total of 341 LANPC patients treated with IC + CCRT were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared by the Kaplan-Meier analysis and the log-rank test, and multivariable survival analysis was carried out to investigate the independent prognostic factors. RESULTS: Univariate analysis showed that a low SUA level and unsatisfactory tumor response to two cycles of IC both were negative predictors for OS, PFS, and DMFS in patients with LANPC. multivariable analysis demonstrated that the SUA level after two cycles of IC was an independent prognostic factor for OS (P = 0.012) but of borderline significance for PFS and DMFS (P = 0.055 and P = 0.067, respectively). Furthermore, tumor response to IC was of independent significance for predicting OS, PFS, and DMFS, respectively. Finally, LANPC patients with satisfactory tumor response and a high SUA level after two cycles of IC had a better OS, PFS, and DMFS than those with unsatisfactory tumor response and a low SUA level. CONCLUSION: The SUA level and the tumor response to two cycles of IC had predictive value for LANPC patients treated with IC plus CCRT. However, more aggressive therapeutic strategies are recommended for those with a low SUA level and unsatisfactory tumor response to two cycles of IC.


Asunto(s)
Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Ácido Úrico/sangre , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/mortalidad , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/mortalidad , Pronóstico , Adulto Joven
11.
Inorg Chem ; 60(2): 550-554, 2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33382257

RESUMEN

Precisely controlling the coordination microenvironment and electronic features of polynuclear secondary building units (SBUs) in coordination polymers (CPs) is an efficient approach to governing their fundamental performance. Here, different multinuclear SBUs (binuclear, trinuclear, and pentanuclear SBUs for 1-3, respectively) were introduced into Cd-based CPs, which were used as frictional electrode materials, to clarify the contributions of polynuclear Cd-SBUs through the output of triboelectric nanogenerators (TENGs). The results demonstrated that 1-TENG with binuclear Cd-SBUs possessed the highest output, whereas 3-TENG with the pentanuclear Cd-SBUs indicated the minimum output, suggesting that the binuclear Cd-SBUs in 1 lost electrons most readily and generated much more charge, which was further confirmed by density functional theory calculations. This work opened a new prospect to confirm the gaining/losing capability of polynuclear Cd-SBUs in CPs and provided an effective approach to tuning both the stability and functionality of polynuclear CPs as frictional pair materials to regulate the output of CPs-based TENGs.

12.
Chemistry ; 26(3): 584-591, 2020 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-31725180

RESUMEN

Selection of the friction electrode materials is crucial to the performance of a triboelectric nanogenerator (TENG). In the present study, a metal-organic coordination complex containing organosulfonate counteranions with electron-donating ability was synthesized through the coordination-driven self-assembly approach under mild reaction conditions and was chosen as a positive electrode material to construct a triboelectric nanogenerator, exhibiting high-output performance with a peak value of short circuit current density of 98.6 µA and an output voltage of 1180 V. As a practical application, it was shown to light up 1488 commercial green LEDs and power an anticorrosion system device to protect metals from corrosion.

13.
Chemistry ; 26(26): 5784-5788, 2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32073179

RESUMEN

Covalent organic frameworks (COFs) enable precise integration of various organic building blocks into porous skeletons through topology predesign. Here, we report the first example of COFs by integrating electron withdrawing bromine group onto the skeletons for triboelectric nanogenerators (TENG). The resulting framework exhibits high surface area and good crystallinity. Thus, the bromine functionalized COF has more regular aligned π columns and arrays over the skeleton than bare COFs, which in turn significantly enhances charge transport ability. As a result, bromine functionalized COFs showed higher electrical output performance at 5 Hz with a peak value of short circuit current density of 43.6 µA and output voltage of 416 V, which is 2 and 1.3 times higher than those of bare COFs (21.6 µA and 318 V), respectively. These results demonstrated that this strategy for engineering electron withdrawing groups on the skeleton could open a new aspect of COFs for developing TENG devices.

14.
Front Pharmacol ; 15: 1363212, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476326

RESUMEN

Both continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson's disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (MD6a) and reported that it has excellent antioxidant activity and significantly reduces α-synuclein aggregation in Caenorhabditis elegans; however, the underlying mechanism is largely unknown. In the present study, we revealed that MD6a is a potential PARP-1 inhibitor, leading to mammalian targe of rapamycin/heat shock factor 1 signaling downregulation and reducing heat shock protein 4 and 6 expression, thus helping to maintain protein homeostasis and improve mitochondrial function. Together, these findings suggest that MD6a might be a viable candidate for the prevention and treatment of Parkinson's disease.

15.
Sci Total Environ ; 918: 170664, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38311080

RESUMEN

The problem of microplastics (MPs) contamination in food has gradually come to the fore. MPs can be transmitted through the food chain and accumulate within various organisms, ultimately posing a threat to human health. The concentration of nanoplastics (NPs) exposed to humans may be higher than that of MPs. For the first time, we studied the differences in toxicity, and potential toxic effects of different polymer types of NPs, namely, polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polystyrene (PS) on HepG2 cells. In this study, PET-NPs, PVC-NPs, and PS-NPs, which had similar particle size, surface charge, and shape, were prepared using nanoprecipitation and emulsion polymerization. The results of the CCK-8 assay showed that the PET-NPs and PVC-NPs induced a decrease in cell viability in a concentration-dependent manner, and their lowest concentrations causing significant cytotoxicity were 100 and 150 µg/mL, respectively. Moreover, the major cytotoxic effects of PET-NPs and PVC-NPs at high concentrations may be to induce an increase in intracellular ROS, which in turn induces cellular damage and other toxic effects. Notably, our study suggested that PET-NPs and PVC-NPs may induce apoptosis in HepG2 cells through the mitochondrial apoptotic pathway. However, no relevant cytotoxicity, oxidative damage, and apoptotic toxic effects were detected in HepG2 cells with exposure to PS-NPs. Furthermore, the analysis of transcriptomics data suggested that PET-NPs and PVC-NPs could significantly inhibit the expression of DNA repair-related genes in the p53 signaling pathway. Compared to PS-NPs, the expression levels of lipid metabolism-related genes were down-regulated to a greater extent by PET-NPs and PVC-NPs. In conclusion, PET-NPs and PVC-NPs were able to induce higher cytotoxic effects than PS-NPs, in which the density and chemical structure of NPs of different polymer types may be the key factors causing the differences in toxicity.


Asunto(s)
Nanopartículas , Contaminantes Químicos del Agua , Humanos , Células Hep G2 , Microplásticos/toxicidad , Plásticos/toxicidad , Apoptosis , Tereftalatos Polietilenos , Polímeros/toxicidad , Poliestirenos/toxicidad
16.
Exp Mol Med ; 56(5): 1150-1163, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38689092

RESUMEN

Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic ß-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.


Asunto(s)
Carcinoma Hepatocelular , Proteínas de Unión al ADN , Epinefrina , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Proteínas de Unión al ARN , Transducción de Señal , Factores de Transcripción , Ubiquitina Tiolesterasa , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Epinefrina/metabolismo , Epinefrina/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Animales , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones , Línea Celular Tumoral , Progresión de la Enfermedad , Masculino , Estrés Fisiológico , Proliferación Celular
17.
Macromolecules ; 56(13): 5033-5049, 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38362140

RESUMEN

In this paper, we present a synergistic, experimental, and computational study of the self-assembly of N,N'-disubstituted polysulfamides driven by hydrogen bonds (H-bonds) between the H-bonding donor and acceptor groups present in repeating sulfamides as a function of the structural design of the polysulfamide backbone. We developed a coarse-grained (CG) polysulfamide model that captures the directionality of H-bonds between the sulfamide groups and used this model in molecular dynamics (MD) simulations to study the self-assembly of these polymers in implicit solvent. The CGMD approach was validated by reproducing experimentally observed trends in the extent of crystallinity for three polysulfamides synthesized with aliphatic and/or aromatic repeating units. After validation of our CGMD approach, we computationally predicted the effect of repeat unit bulkiness, length, and uniformity of segment lengths in the polymers on the extent of orientational and positional order among the self-assembled polysulfamide chains, providing key design principles for tuning the extent of crystallinity in polysulfamides in experiments. Those computational predictions were then experimentally tested through the synthesis and characterization of polysulfamide architectures.

18.
Int J Biol Macromol ; 233: 123595, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36773870

RESUMEN

Various methods have been used to cope with heavy metal ion contamination in wastewater, which caused serious hazards to ecological and human health. Adsorption is one of the most frequent, economical and effective methods for removing these contaminants. Herein, a porous and amino-rich cellulose-based composite adsorbent (PEI-PCS) with anisotropic property was successfully prepared by covalently cross-linking polyethyleneimine on delignified corn straw. Combined with the porosity of straw substrate and the chelating ability of amino group to metal ions, the as-prepared PEI-PCS exhibited universality (various metal ions), rapid adsorption behavior (within 180 min achieve adsorption equilibrium), high adsorption capacity (85.47 mg g-1 for Cu(II)), and good durability (70 % of adsorption efficiency after 5 cycles). In addition, the adsorption process was conformed to pseudo-second-order dynamics and the Langmuir isotherm models. Lastly, the adsorption mechanism was also elucidated. This study provides a sustainable pathway for the manufacture of efficient biomass-based adsorbents and confirms that functionalized corn straw is a promising material for the treatment of heavy metal ions.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Purificación del Agua , Humanos , Celulosa/química , Zea mays , Porosidad , Adsorción , Contaminantes Químicos del Agua/química , Metales Pesados/química , Iones , Purificación del Agua/métodos , Cinética , Concentración de Iones de Hidrógeno
19.
J Hepatocell Carcinoma ; 10: 2197-2209, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38090626

RESUMEN

Background: Hepatocellular carcinoma (HCC) is one of the most serious malignant tumors threatening human life with a high mortality rate. The liver regenerative capacity after hepatectomy in early-stage HCC patients is influenced by various factors, including surgical methods and energy metabolism. This study aims to provide a prognostic model based on genes related to liver regeneration that can predict the prognosis of non-tumor tissues in HCC patients. Patients and Methods: A total of 584 non-tumor tissues from HCC patients were collected from three independent databases. Kaplan-Meier survival curves were used to identify prognostic liver-regeneration genes. Subsequently, a prognostic indicator, designated as the Liver Regeneration score (LR score), was determined using single-sample gene set enrichment analysis (ssGSEA). Independent cohorts were used to verify the relationship between LR score and prognosis in non-tumor tissues of HCC patients. Furthermore, a liver regeneration-related model was established to validate key genes identified through LASSO Cox regression analysis. Results: We constructed a gene set comprising 24 liver regeneration-related genes, and the LR score was utilized to predict the prognosis of HCC patients based on its levels in non-tumor tissues. In non-tumor tissues of HCC patients, higher LR scores were associated with improved prognosis. Higher LR scores in non-tumor tissues indicate improved liver metabolism in HCC patients, revealed by Enrichment analysis. LASSO Cox regression analysis identified two key genes, DHTKD1 (dehydrogenase E1 and transketolase domain containing 1) and PHYH (phytanoyl-CoA 2-hydroxylase), and higher expression levels of these genes in non-tumor tissues were correlated with better prognosis. The expression levels of these two genes also changed corresponding to the progression of liver regeneration. Conclusion: In summary, our study has introduced a novel LR gene signature for HCC patients, providing a predictive model for estimating clinical prognosis from non-tumor tissues. The LR score demonstrates promise as a reliable indicator for predicting overall survival in HCC.

20.
Sci Total Environ ; 864: 161111, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36572308

RESUMEN

Plastic waste can carry organisms such as bacterial pathogens and antibiotic resistance genes (ARGs) over long distances. However, only few studies have been conducted on the occurrence of ARGs in plastic waste from mangrove wetlands. This study evaluated the distribution characteristics and ecological risks of plastic waste from mangroves in the coastal areas of the South China Sea. The correlation between anthropogenic activity levels and abundance of ARGs in mangroves was evaluated. Transparent and white were the common colors of plastic waste in mangroves. The main shapes of plastic waste were foam and film. The predominant types of plastic waste order were as follows: polyethylene (30.18 %) > polypropylene (27.51 %) > polystyrene (23.59 %). The living area (LA) mangroves had the highest polymer hazard and pollution load indices of 329.09 and 10.03, respectively. The abundance of ARGs (5.08 × 108 copies/g) on the plastic surface in LA mangroves was significantly higher than that of the other mangrove areas. Furthermore, there was a significant correlation between ARGs and intI1 on the plastic surface in mangroves. Correlation analysis between the ARGs and intI1 showed that most of the ARGs were correlated with intI1 except for msbA. In LA mangroves, sociometric and environmental factors showed significant correlations with the absolute abundances of the four ARGs and intI1, indicating that anthropogenic activities may lead to changes in the amount of ARGs on plastic surfaces. Furthermore, the ARG storage of plastic waste from different mangroves was as follows: protected areas (3.12 × 1017 copies) > living areas (2.99 × 1017 copies) > aquaculture pond areas (2.88 × 1017 copies). The higher ARG storage of LA mangroves, with the smallest area, greatly increased its ecological risk. The results of this study can provide basic data for processes that influence the distribution of plastic waste and ARGs in mangroves.


Asunto(s)
Antibacterianos , Humedales , Genes Bacterianos , Plásticos , Farmacorresistencia Microbiana/genética , China
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA