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1.
Fish Shellfish Immunol ; 150: 109569, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641216

RESUMO

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.

2.
Exp Mol Med ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38689092

RESUMO

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.

3.
Genomics ; 116(3): 110831, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513875

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/genética , Humanos , Vírus da Hepatite B/genética , Fenótipo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Hepatite B/virologia , Hepatite B/complicações , Hepatite B/genética , Instabilidade Genômica , Reparo do DNA , Multiômica
4.
Front Pharmacol ; 15: 1363212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476326

RESUMO

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.

5.
Biomacromolecules ; 25(3): 1682-1695, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38417021

RESUMO

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.


Assuntos
Metilcelulose , Simulação de Dinâmica Molecular , Metilcelulose/química , Água/química , Celulose
6.
Sci Total Environ ; 918: 170664, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38311080

RESUMO

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.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Humanos , Células Hep G2 , Microplásticos/toxicidade , Plásticos/toxicidade , Apoptose , Polietilenotereftalatos , Polímeros/toxicidade , Poliestirenos/toxicidade
7.
Ecotoxicol Environ Saf ; 269: 115814, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100851

RESUMO

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.


Assuntos
Arsênio , Humanos , Arsênio/toxicidade , Células Hep G2 , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidade , Apoptose
8.
J Hepatocell Carcinoma ; 10: 2197-2209, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090626

RESUMO

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.

9.
Sci Total Environ ; 905: 167010, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37722421

RESUMO

As an emerging environmental pollutant, nanoplastics (NPs) have attracted wide attention in terms of their impact on the ecological environment and human health. Currently, researches on the cytotoxicity of NPs mainly focus on oxidative stress, damage to the cell membrane and organelles, induction of immune response and genotoxicity. Okadaic acid (OA) is the main component of diarrheal shellfish toxin. Based on the previous combined toxicity exploration of polystyrene (PS) NPs and (OA) to human gastric adenocarcinoma (AGS) cells, cell-derived exosomes were extracted and exosomal miRNA profiles were analyzed for the first time in this study. The results showed that the composition of miRNAs varied after the exposure of NPs and OA. Specifically, the expression of miR-1-3p in both PS-Exo and PS-OA-Exo was significantly reduced. And the expression of miR-1248 was upregulated most significantly by comparing the DE miRNAs between PS-Exo and PS-OA-Exo. MiR-1-3p and miR-1248 may be the key genes for the combined toxicity of NPs and OA. After analysis, we found that both the decreased expression of miR-1-3p and the increased expression of miR-1248 can increase the expression of FN1 and affect DNA replication, which was surprisingly consistent with the results of our previous cytotoxicity studies. Since exosomal miRNAs are selectively encapsulated by donor cell, we speculate that the changes of exosomal miRNAs may due to the synchronous changes of intracellular environment and the downregulation of intracellular FN1 may be attributed to decreased expression of miR-1-3p and increased expression of miR-1248 in donor cells. Accordingly, we come to the conclusion that the changes of miRNAs in the exosomes derived from AGS cells after environmental stimulation could reflect the biological effects of donor cells.


Assuntos
MicroRNAs , Humanos , MicroRNAs/genética , Microplásticos/toxicidade , Microplásticos/metabolismo , Ácido Okadáico/toxicidade , Regulação para Baixo
10.
Radiat Oncol ; 18(1): 104, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353800

RESUMO

BACKGROUND: We aimed to evaluate the optimal management for elderly patients with nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT). METHODS: A total of 283 elderly patients with NPC diagnosed from 2015 to 2019 were enrolled in the study. Overall survival (OS) was the primary endpoint. Univariate and multivariate Cox regression analyses were preformed to identify potential prognostic factors. The recursive partitioning analysis (RPA) was used for risk stratification. Kaplan-Meier survival curves were applied to evaluate the survival endpoints, and log-rank test was utilized to assess differences between groups. The prognostic index (PI) was constructed to further predict patients' prognosis displayed by nomogram model. The area under the receiver operating characteristic (ROC) curves (AUC) and the calibration curves were applied to assess the effectiveness of the model. RESULTS: Based on RPA-based risk stratification, we demonstrated that elderly NPC patients who were treated with IC followed by RT had similar OS as those with induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) in the middle- (stage I-III and pre-treatment EBV > 1840 copies/ml) and high-risk groups (stage IVA). IMRT alone may be the optimal treatment option for the low-risk group (stage I-III with pre-treatment EBV ≤ 1840 copies/ml). We established an integrated PI which was indicted with stronger prognostic power than each of the factors alone for elderly NPC patients (The AUC of PI was 0.75, 0.80, and 0.82 for 1-, 3-, 5-year prediction of OS, respectively). CONCLUSION: We present a robust model for clinical stratification which could guide individual therapy for elderly NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Idoso , Carcinoma Nasofaríngeo/patologia , Prognóstico , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , Quimiorradioterapia , Medição de Risco
11.
ACS Appl Mater Interfaces ; 15(22): 26227-26240, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37226779

RESUMO

Osteosarcoma is prone to metastasis and has a low long-term survival rate. The drug treatment of osteosarcoma, side effects of treatment drugs, and prognosis of patients with lung metastasis continue to present significant challenges, and the efficacy of drugs used in the treatment of osteosarcoma remains low. The development of new therapeutic drugs is urgently needed. In this study, we successfully isolated Pinctada martensii mucilage exosome-like nanovesicles (PMMENs). Our findings demonstrated that PMMENs inhibited the viability and proliferation of 143B cells, induced apoptosis, and inhibited cell proliferation by suppressing the activation of the ERK1/2 and Wnt signaling pathways. Furthermore, PMMENs inhibited cell migration and invasion by downregulating N-cadherin, vimentin, and matrix metalloprotease-2 protein expression levels. Transcriptomic and metabolomic analyses revealed that differential genes were co-enriched with differential metabolites in cancer signaling pathways. These results suggest that PMMENs may exert anti-tumor activity by targeting the ERK1/2 and Wnt signaling pathways. Moreover, tumor xenograft model experiments showed that PMMENs can inhibit the growth of osteosarcoma in mice. Thus, PMMENs may be a potential anti-osteosarcoma drug.


Assuntos
Neoplasias Ósseas , Exossomos , Osteossarcoma , Pinctada , Humanos , Animais , Camundongos , Exossomos/metabolismo , Linhagem Celular Tumoral , Neoplasias Ósseas/patologia , Apoptose , Proliferação de Células , Via de Sinalização Wnt , Osteossarcoma/metabolismo , Movimento Celular
12.
Cancer Immunol Immunother ; 72(8): 2741-2755, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37119260

RESUMO

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.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Humanos , Epitopos de Linfócito T , Nitratos , Antígenos de Neoplasias , Neoplasias/tratamento farmacológico , Linfócitos T Auxiliares-Indutores , Adjuvantes Imunológicos , DNA , Imunoterapia
13.
Int J Biol Macromol ; 233: 123595, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36773870

RESUMO

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.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Purificação da Água , Humanos , Celulose/química , Zea mays , Porosidade , Adsorção , Poluentes Químicos da Água/química , Metais Pesados/química , Íons , Purificação da Água/métodos , Cinética , Concentração de Íons de Hidrogênio
14.
Sci Total Environ ; 864: 161111, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36572308

RESUMO

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.


Assuntos
Antibacterianos , Áreas Alagadas , Genes Bacterianos , Plásticos , Resistência Microbiana a Medicamentos/genética , China
15.
Ecotoxicol Environ Saf ; 249: 114375, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508836

RESUMO

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.


Assuntos
Apoptose , Microplásticos , Ácido Okadáico , Poliestirenos , Poluentes Químicos da Água , Humanos , Apoptose/efeitos dos fármacos , Células CACO-2 , Microplásticos/toxicidade , Ácido Okadáico/toxicidade , Plásticos , Poliestirenos/toxicidade , Poluentes Químicos da Água/toxicidade
16.
Macromolecules ; 56(13): 5033-5049, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38362140

RESUMO

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.

17.
Biochem Biophys Res Commun ; 634: 10-19, 2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-36228540

RESUMO

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.


Assuntos
Dermatite , Vesículas Extracelulares , Pinctada , Animais , Humanos , Vesículas Extracelulares/metabolismo , Inflamassomos/metabolismo , Inflamação , Muco/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pinctada/metabolismo , Proteínas Quinases Ativadas por Mitógeno
18.
Inorg Chem ; 61(5): 2490-2498, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35067051

RESUMO

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.

19.
JACS Au ; 1(11): 1925-1936, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34841410

RESUMO

In this paper we present the development and validation of the "Computational Reverse-Engineering Analysis for Scattering Experiments" (CREASE) method for analyzing scattering results from vesicle structures that are commonly found upon assembly of synthetic, biomimetic, or bioderived amphiphilic copolymers in solution. The two-step CREASE method takes the amphiphilic polymer chemistry and small-angle scattering intensity profile, I exp(q), as input and determines the vesicles' structural features on multiple length scales ranging from assembled vesicle wall's individual layer thicknesses to the monomer-level packing and distribution of polymer conformations. In the first step of CREASE, a genetic algorithm (GA) is used to determine the relevant vesicle dimensions from the input macromolecular solution information and I exp(q) by identifying the structure whose computed scattering profile best matches the input I exp(q). Then in the second step, the GA-determined dimensions are used for molecular reconstruction of the vesicle structure. To validate CREASE for vesicles, we test CREASE on input scattering intensity profiles generated mathematically (termed as in silico I exp(q) vs q) from a variety of vesicle sizes with known dimensions. We also test CREASE on in silico I exp(q) vs q generated from vesicles with dispersity in all relevant dimensions, resembling real experiments. After successful validation of CREASE, we compare the CREASE-determined dimensions against those obtained from the traditional approach of fitting the scattering intensity profile to relevant analytical model in SASVIEW package. We show that CREASE performs better than or as well as the core-multishell analytical model's fitting in SASVIEW in determining vesicle dimensions with dispersity. We also show that CREASE provides structural information beyond those possible from traditional scattering analysis using the core-multishell model, such as the distribution of solvophilic monomers between the vesicle wall's inner and outer layers in the vesicle wall and the chain-level packing within each vesicle layer.

20.
BMC Cancer ; 21(1): 519, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33962583

RESUMO

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.


Assuntos
Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Ácido Úrico/sangue , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Prognóstico , Adulto Jovem
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