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1.
Electrophoresis ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39286940

RESUMO

The large surface area, excellent thermal stability and easy modification make microporous organic networks (MONs) good candidates in the field of gas chromatography (GC). Due to the limited species and highly conjugated networks of MONs, their applications are still in infancy and restricted. To accelerate their developments and to enrich their types in GC, here we report the first example of synthesizing alkyl MON and its capillary column for GC separation of position isomers. Linear 1,8-dibromooctane is used as the alkyl monomer instead of traditional aromatic ones to construct novel alkyl MON to decrease the inherent conjugated characteristic of MONs. The alkyl MON exhibits good thermal stability (up to 350°C), large surface area (1173 m2 g-1), and non-polar character, allowing good resolution for alkanes, alkyl benzenes, alcohols, ketones, and diverse position isomers, including dichlorobenzene, trichlorobenzene, bromotoluene, nitrotoluene, methylbenzaldehyde, and ionone with the limits of detection (0.003 mg mL-1) and limits of quantitation of (0.10 mg mL-1). The in situ growth-prepared alkyl MON column demonstrates remarkable duration time and precisions for the retention relative standard deviations, (RSDs%, intra-day, n = 7), 0.06%-0.53% (intra-day, n = 7), and 2.87%-10.59% (column-to-column, n = 3). In addition, the fabricated alkyl MON-coated capillary column offers better resolution than three commercial GC columns for the resolution of methylbenzaldehyde, bromotoluene, and chlorotoluene isomers. This work reveals the practicability for synthesizing alkyl MONs and demonstrates their prospects for position isomers separation.

2.
Lab Chip ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291395

RESUMO

In disciplines like toxicology and pharmacology, oxygen (O2) respiration is a universal metric for evaluating the effects of chemicals across various model systems, including mammalian and microalgal cells. However, for these cells the common practice is to segregate populations into control and exposure groups, which assumes direct equivalence in their responses and does not take into account heterogeneity among individual cells. This lack of resolution impedes our ability to precisely investigate differences among experimental groups with small or limited sample sizes. To overcome this barrier, we introduce SlipO2Chip, an innovative glass microfluidic platform for precisely quantifying single-cell O2 respiration in the coordinated absence and presence of chemical solutes. SlipO2Chip comprises a wet-etched fused silica channel plate on the top and a dry-etched borosilicate microwell plate at the bottom. The microwells are coated with Pt(II) meso-tetra(pentafluorophenyl)porphine (PtTFPP), an O2 sensing optode material and an O2-independent reference dye. A custom 3D-printed holder facilitates the controlled horizontal movement ('slipping') of the channel plate over the microwell plate, thereby establishing or disrupting the fluid path over microwells. Collectively, these design elements enable the immobilization of single-cells in microwells, their exposure to controlled fluid flows, the coordinated opening and closing of microwells and repeated measurements of single-cell O2 respiration. Uniquely, by sequentially executing opening and closing it becomes possible to measure single-cell respiration prior to and after exposure to chemical solutes. In a proof-of-concept application, we utilized SlipO2Chip to measure the impact of increasing exposures of the marine bacterial signal 2-heptyl-4-quinolone (HHQ) on the dark respiration of the diatom Ditylum brightwellii at single-cell resolution. Results revealed a concentration-dependent decrease in per-cell O2 dark respiration, with a maximum reduction of 40.2% observed at HHQ concentrations exceeding 35.5 µM, and a half-maximal effective concentration (EC50) of 5.8 µM, consistent with that obtained via conventional bulk respiration methods. The ability of SlipO2Chip to sequentially assess the effects of chemical substances on single-cell O2 metabolism is advantageous for research where sample volumes are limited, such as clinical biopsies, studies involving rare microbial isolates, and toxicological studies aiming to address exposure effects while accounting for cell-to-cell variability.

3.
Anal Chim Acta ; 1326: 343138, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39260916

RESUMO

BACKGROUND: Sulfonamide (SA) residues in food of animal origin possess a potential threat to human health and environment. However, due to the polar and ionic characteristics and trace level of SAs and the complexity of food matrices, direct measurement of SAs in these samples is still very difficult. Development of efficient sample pretreatment method for sensitive and selective extraction of trace SAs is of great significance and urgently desired. Therefore, rational design and synthesizing advanced and selective extractants is quite important. RESULTS: In this work, a novel phenazine-based microporous organic network (MON) named TEPM-DP is reasonably synthesized and employed as a packing material for selective solid phase extraction (SPE) and sensitive determination of four typical SAs in milk samples. Phenazine-based monomer with aromatic and heteroaromatic ring and numerous N atoms is chosen to construct TEPM-DP adsorbent to provide π-π, hydrogen bonding, hydrophobic, and electrostatic extraction sites for SAs. The proposed method owns wide linear ranges, low limits of detection, high enrichment factors, and good precisions and recoveries for SAs in complex milk samples. The recoveries of SAs on TEPM-DP are much higher than those of commercial C18 and activated carbon. The extraction mechanisms are also elucidated via FT-IR, XPS, and comparative experiments. SIGNIFICANCE: This work reports the first example of design and synthesizing phenazine-based MON in SPE via a simple and rapid solvothermal method. The results reveal the great prospects of TEPM-DP for enriching polar and ionic SAs in complex samples and uncover the potency of phenazine-based MON in sample pretreatment, which will promote the development of MON.


Assuntos
Leite , Fenazinas , Extração em Fase Sólida , Sulfonamidas , Fenazinas/química , Leite/química , Animais , Sulfonamidas/análise , Sulfonamidas/isolamento & purificação , Extração em Fase Sólida/métodos , Porosidade , Limite de Detecção , Adsorção , Contaminação de Alimentos/análise
4.
Artigo em Inglês | MEDLINE | ID: mdl-39255101

RESUMO

Visualization items-factual questions about visualizations that ask viewers to accomplish visualization tasks-are regularly used in the field of information visualization as educational and evaluative materials. For example, researchers of visualization literacy require large, diverse banks of items to conduct studies where the same skill is measured repeatedly on the same participants. Yet, generating a large number of high-quality, diverse items requires significant time and expertise. To address the critical need for a large number of diverse visualization items in education and research, this paper investigates the potential for large language models (LLMs) to automate the generation of multiple-choice visualization items. Through an iterative design process, we develop the VILA (Visualization Items Generated by Large LAnguage Models) pipeline, for efficiently generating visualization items that measure people's ability to accomplish visualization tasks. We use the VILA pipeline to generate 1,404 candidate items across 12 chart types and 13 visualization tasks. In collaboration with 11 visualization experts, we develop an evaluation rulebook which we then use to rate the quality of all candidate items. The result is the VILA bank of ∼1,100 items. From this evaluation, we also identify and classify current limitations of the VILA pipeline, and discuss the role of human oversight in ensuring quality. In addition, we demonstrate an application of our work by creating a visualization literacy test, VILA-VLAT, which measures people's ability to complete a diverse set of tasks on various types of visualizations; comparing it to the existing VLAT, VILA-VLAT shows moderate to high convergent validity (R = 0.70). Lastly, we discuss the application areas of the VILA pipeline and the VILA bank and provide practical recommendations for their use. All supplemental materials are available at https://osf.io/ysrhq/.

6.
J Hazard Mater ; 478: 135375, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39141942

RESUMO

The brominated flame retardant 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) widely used in manufacturing is inevitably released into the environment, resulting in the exposure of organisms to BTBPE. Therefore, it is particularly important to explore its toxic mechanism. The liver is one of the main accumulating organs of BTBPE, but the mechanism underlying BTBPE hepatotoxicity has not been thoroughly investigated. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat hepatocytes (BRL cells) in vivo and in vitro, respectively, and HE staining, AO/EB staining, fluorescent probes, qPCR, immunofluorescence, and dual-luciferase reporter assays were performed. We investigated the mechanism of action of growth arrest-specific 5 (GAS5), miR-743a-5p, and NUAK family kinase 1 (NUAK1) in BTBPE-induced necroptosis from the perspective of competing endogenous RNAs (ceRNAs) using NUAK1 inhibitors, siRNAs, mimics, and overexpression plasmids. Our study showed that exposure to BTBPE caused necroptosis in the liver and BRL cells, accompanied by an oxidation-reduction imbalance and an inflammatory response. It is worth noting that NUAK1 is a newly discovered upstream regulatory target for necroptosis. In addition, miR-743a-5p was shown to inhibit necroptosis by targeting NUAK1 and down-regulating NUAK1. GAS5 upregulates NUAK1 expression by competitively binding to miR-743a-5p, thereby inducing necroptosis. This study demonstrated, for the first time, that the GAS5-miR-743a-5p-NUAK1 axis is involved in the regulation of necroptosis via ceRNAs. Thus, GAS5 and NUAK1 induce necroptosis by competitively binding to miR-743a-5p.


Assuntos
Hepatócitos , MicroRNAs , Necroptose , Animais , Masculino , Ratos , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular , Retardadores de Chama/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , MicroRNAs/metabolismo , MicroRNAs/genética , Necroptose/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Ratos Sprague-Dawley , RNA Nucleolar Pequeno
7.
Int J Biol Macromol ; 277(Pt 4): 134409, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39097042

RESUMO

Alginate is a linear polysaccharide with a modifiable structure and abundant functional groups, offers immense potential for tailoring diverse alginate-based materials to meet the demands of biomedical applications. Given the advancements in modification techniques, it is significant to analyze and summarize the modification of alginate by physical, chemical and biological methods. These approaches provide plentiful information on the preparation, characterization and application of alginate-based materials. Physical modification generally involves blending and physical crosslinking, while chemical modification relies on chemical reactions, mainly including acylation, sulfation, phosphorylation, carbodiimide coupling, nucleophilic substitution, graft copolymerization, terminal modification, and degradation. Chemical modified alginate contains chemically crosslinked alginate, grafted alginate and oligo-alginate. Biological modification associated with various enzymes to realize the hydrolysis or grafting. These diverse modifications hold great promise in fully harnessing the potential of alginate for its burgeoning biomedical applications in the future. In summary, this review provides a comprehensive discussion and summary of different modification methods applied to improve the properties of alginate while expanding its biomedical potentials.


Assuntos
Alginatos , Materiais Biocompatíveis , Alginatos/química , Materiais Biocompatíveis/química , Humanos , Animais , Hidrólise
8.
Chin Med ; 19(1): 119, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39215362

RESUMO

Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects.

9.
Toxicol Appl Pharmacol ; 490: 117020, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38969211

RESUMO

This study explored the effects of 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) and bis (2-ethylhexyl) tetrabromophthalate (TBPH) on serum metabolites and lipids in male Sprague-Dawley (SD) rats. Rats were orally gavaged 250 mg/kg bw of BTBPE and 500 mg/kg bw of TBPH for 28 consecutive days. Serum samples were collected for metabolomics and lipidomics analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to explore changes in rat metabolic patterns. Least absolute shrinkage and selection operator (LASSO) regression models were established using serum levels of total thyroxine (TT4), free thyroxine (FT4), and rats' grouping information as variables to screen for robust differential substances. SuperPred was the database to obtain potential targets. The metabolomics and lipidomics results showed that BTBPE and TBPH had an impact on rat metabolic patterns, affecting pathways such as vitamin B6 synthesis. For BTBPE treatment, pyridoxal and ceramide (Cer) 24:0;4O were selected as differential substances related to thyroid hormones. For TBPH treatment, dehydroascorbic acid, acylcarnitine (CAR) 19:0, and diglyceride (DG) 38:4 were selected as differential substances related to thyroid hormones. Serotonin 2c receptor and cyclooxygenase-2 were chosen as potential targets of BTBPE and TBPH, respectively. In conclusion, this study found that BTBPE and TBPH impacted the metabolism of rats, and this effect may be related to changes in thyroid function.


Assuntos
Metabolômica , Ácidos Ftálicos , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Ácidos Ftálicos/toxicidade , Tiroxina/sangue , Lipidômica , Lipídeos/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos
10.
Drug Des Devel Ther ; 18: 3269-3293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081706

RESUMO

Background: Qingchang Tongluo Decoction (QTF) is clinically used for the treatment of intestinal fibrosis in Crohn's Disease (CD). However, the role of QTF in CD-associated fibrosis and its potential pharmacological mechanism remains unclear. Purpose: The objective of this study was to elucidate the potential mechanism of QTF in treating CD-associated fibrosis, employing a combination of bioinformatics approaches - encompassing network pharmacology and molecular docking - complemented by experimental validation. Methods: To investigate the material basis and potential protective mechanism of QTF, a network pharmacology analysis was conducted. The core components and targets of QTF underwent molecular docking analysis to corroborate the findings obtained from network pharmacology. In vitro, a colon fibrotic model was established by stimulating IEC-6 cells with 10 ng/mL of transforming growth factor(TGF-ß1). In vivo, an intestinal fibrosis model was induced in BALB/c mice by TNBS. The role of QTF in inhibiting the TGF-ß1/Smad signaling pathway was investigated through RT-qPCR, Western blotting, immunohistochemistry staining, and immunofluorescence staining. Results: Network pharmacology analysis revealed that QTF could exert its protective effect. Bioinformatics analysis suggested that Flavone and Isoflavone might be the key components of the study. Additionally, AKT1, IL-6, TNF, and VEGFA were identified as potential therapeutic targets. Furthermore, experimental validation and molecular docking were employed to corroborate the results obtained from network pharmacology. RT-qPCR, Immunofluorescence, and Western blotting results demonstrated that QTF significantly improved colon function and inhibited pathological intestinal fibrosis in vivo and in vitro. Conclusion: Through the application of network pharmacology, molecular docking, and experimental validation, QTF could be confirmed to inhibit the proliferation of intestinal fibroblasts associated with CD and reduce the expression of Collagen I and VEGFA. This effect is achieved through the attenuation of ECM accumulation, primarily via the inhibition of the TGF-ß1/Smad signaling pathway.


Assuntos
Doença de Crohn , Medicamentos de Ervas Chinesas , Fibrose , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Animais , Fibrose/tratamento farmacológico , Camundongos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Doença de Crohn/metabolismo , Ratos , Masculino , Fator de Crescimento Transformador beta1/metabolismo , Modelos Animais de Doenças
11.
Lab Chip ; 24(17): 4128-4137, 2024 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-39069914

RESUMO

Accurate descriptions of the variability in single-cell oxygen consumption and its size-dependency are key to establishing more robust tissue models. By combining microfabricated devices with multiparameter identification algorithms, we demonstrate that single human hepatocytes exhibit an oxygen level-dependent consumption rate and that their maximal oxygen consumption rate is significantly lower than that of typical hepatic cell cultures. Moreover, we found that clusters of two or more cells competing for a limited oxygen supply reduced their maximal consumption rate, highlighting their ability to adapt to local resource availability and the presence of nearby cells. We used our approach to characterize the covariance of size and oxygen consumption rate within a cell population, showing that size matters, since oxygen metabolism covaries lognormally with cell size. Our study paves the way for linking the metabolic activity of single human hepatocytes to their tissue- or organ-level metabolism and describing its size-related variability through scaling laws.


Assuntos
Hepatócitos , Consumo de Oxigênio , Humanos , Hepatócitos/metabolismo , Hepatócitos/citologia , Tamanho Celular , Oxigênio/metabolismo , Análise de Célula Única , Células Cultivadas
12.
J Chromatogr A ; 1730: 465140, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38986401

RESUMO

In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe3O4, MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 µg L-1), low limits of detection (0.07-1.7 µg L-1), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment.


Assuntos
Compostos de Anilina , Anti-Inflamatórios não Esteroides , Extração em Fase Sólida , Compostos de Anilina/química , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Suínos , Galinhas , Bovinos , Adsorção , Carne/análise , Porosidade , Reprodutibilidade dos Testes
13.
Sci Total Environ ; 946: 174350, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38960203

RESUMO

There is limited evidence on the effects of intrauterine chromium (Cr) exposure on children's cognitive developmental delay (CDD). Further, little is known about the genetic factors in modifying the association between intrauterine Cr exposure and CDD. The present study involved 2361 mother-child pairs, in which maternal plasma Cr concentrations were assessed, a polygenic risk score for the child was constructed, and the child's cognitive development was evaluated using the Bayley Scales of Infant Development. The risks of CDD conferred by intrauterine Cr exposure in children with different genetic backgrounds were evaluated by logistic regression. The additive interaction between intrauterine Cr exposure and genetic factors was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). According to present study, higher intrauterine Cr exposure was significantly associated with increased CDD risk [each unit increase in ln-transformed maternal plasma Cr concentration (ln-Cr): adjusted OR (95 % CI), 1.18 (1.04-1.35); highest vs lowest quartile: adjusted OR (95 % CI), 1.57 (1.10-2.23)]. The dose-response relationship of intrauterine Cr exposure and CDD for children with high genetic risk was more prominent [each unit increased ln-Cr: adjusted OR (95 % CI), 1.36 (1.09-1.70)]. Joint effects between intrauterine Cr exposure and genetic factors were found. Specifically, for high genetic risk carriers, the association between intrauterine Cr exposure and CDD was more evident [highest vs lowest quartile: adjusted OR (95 % CI), 2.33 (1.43-3.80)]. For those children with high intrauterine Cr exposure and high genetic risk, the adjusted AP was 0.39 (95 % CI, 0.07-0.72). Conclusively, intrauterine Cr exposure was a high-risk factor for CDD in children, particularly for those with high genetic risk. Intrauterine Cr exposure and one's adverse genetic background jointly contribute to an increased risk of CDD in children.


Assuntos
Cromo , Predisposição Genética para Doença , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Efeitos Tardios da Exposição Pré-Natal/genética , Gravidez , Cromo/toxicidade , Exposição Materna/estatística & dados numéricos , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/induzido quimicamente , Masculino , Adulto , Pré-Escolar , Poluentes Ambientais/toxicidade , Lactente
14.
J Chromatogr A ; 1730: 465158, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39025023

RESUMO

The overuse of nonsteroidal anti-inflammatory drugs (NSAIDs) poses many serious environmental and food safety concerns. Development of effective and sensitive sample pretreatment method for monitoring trace NSAIDs from complex samples is of great significance. Depending on the ionic and aromatic structures of NSAIDs, a cationic microporous organic network (MON) named TEPM-BBDC with large specific surface area, good solvent and thermal stabilities, and numerous interaction sites was designed and prepared for efficient solid-phase extraction (SPE) of four typical NSAIDs (flurbiprofen, ketoprofen, naproxen, and diclofenac sodium) from environmental water and milk samples. By anchoring the ionic groups in the conjugated MON frameworks, the prepared TEPM-BBDC offered good extraction for NSAIDs based on the π-π, hydrophobic, ion exchange, and electrostatic interactions. Under the optimal extraction conditions (initial concentration of each NSAID: 200 g L-1; sample volume: 50 mL; desorption solvent: 1.5 mL of MeOH + 1 % NH3·H2O; sample loading rate: 5 mL min-1; NaCl concentration: 0 mmol L-1; pH = 5), the proposed TEPM-BBDC-SPE-HPLC-UV method owned wide linear range (0.50-1000 g L-1), low limits of detection (0.10-0.40 g L-1), large enrichment factors (92.2-99.2), good precisions (intra-day and inter-day, RSD% = 1.3-7.8 %, n = 6) and reproducibility (column-to-column, RSD% = 8.0 %, n = 3). The developed method also exhibited good recoveries (83.6-113.4 %) for the determination of NSAIDs in river water, lake water and milk samples. This work not only revealed the potential of TEPM-BBDC for SPE of ionic NSAIDs in complex samples, but also highlighted the prospect of ionic MONs in sample pretreatment.


Assuntos
Anti-Inflamatórios não Esteroides , Limite de Detecção , Leite , Extração em Fase Sólida , Poluentes Químicos da Água , Extração em Fase Sólida/métodos , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/isolamento & purificação , Leite/química , Animais , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/química , Cromatografia Líquida de Alta Pressão/métodos , Porosidade , Cátions/química , Reprodutibilidade dos Testes , Adsorção
15.
J Pers Med ; 14(7)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39063948

RESUMO

By using omics, we can now examine all components of biological systems simultaneously. Deep learning-based drug prediction methods have shown promise by integrating cancer-related multi-omics data. However, the complex interaction between genes poses challenges in accurately projecting multi-omics data. In this research, we present a predictive model for drug response that incorporates diverse types of omics data, comprising genetic mutation, copy number variation, methylation, and gene expression data. This study proposes latent alignment for information mismatch in integration, which is achieved through an attention module capturing interactions among diverse types of omics data. The latent alignment and attention modules significantly improve predictions, outperforming the baseline model, with MSE = 1.1333, F1-score = 0.5342, and AUROC = 0.5776. High accuracy was achieved in predicting drug responses for piplartine and tenovin-6, while the accuracy was comparatively lower for mitomycin-C and obatoclax. The latent alignment module exclusively outperforms the baseline model, enhancing the MSE by 0.2375, the F1-score by 4.84%, and the AUROC by 6.1%. Similarly, the attention module only improves these metrics by 0.1899, 2.88%, and 2.84%, respectively. In the interpretability case study, panobinostat exhibited the most effective predicted response, with a value of -4.895. We provide reliable insights for drug selection in personalized medicine by identifying crucial genetic factors influencing drug response.

16.
J Med Chem ; 67(14): 12248-12260, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38959374

RESUMO

Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.


Assuntos
Antozoários , Colite Ulcerativa , Sulfato de Dextrana , Diterpenos , Animais , Colite Ulcerativa/tratamento farmacológico , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/uso terapêutico , Diterpenos/isolamento & purificação , Camundongos , Relação Estrutura-Atividade , Antozoários/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/isolamento & purificação , Células RAW 264.7 , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Descoberta de Drogas , Camundongos Endogâmicos C57BL , Humanos , Masculino , Óxido Nítrico/metabolismo
17.
Microb Pathog ; 194: 106825, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39074517

RESUMO

Short beak and dwarfism syndrome (SBDS) is attributed to Novel Goose Parvovirus (NGPV), which has inflicted significant economic losses on farming in China. Despite its significant impact, limited research has been conducted on the pathogenesis of this disease. The SD strain, a parvovirus variant isolated from ducks in Shandong province, was identified and characterized in our study. Phylogenetic analysis and sequence comparisons confirmed the classification of the SD strain as a member of NGPV. Based on this information, we established an animal model of SBDS by inoculating Cherry Valley ducks with the SD strain. Our findings indicate that infection with the SD strain leads to a reduction in body weight, beak length, width, and tibia length. Notably, significant histopathological alterations were observed in the thymus, spleen, and intestine of the infected ducks. Furthermore, the SD strain induces bone disorders and inflammatory responses. To evaluate the impact of NGPV on intestinal homeostasis, we performed 16S rDNA sequencing and gas chromatography to analyze the composition of intestinal flora and levels of short-chain fatty acids (SCFAs) in the cecal contents. Our findings revealed that SD strain infection induces dysbiosis in cecal microbial and a decrease in SCFAs production. Subsequent analysis revealed a significant correlation between bacterial genera and the clinical symptoms in NGPV SD infected ducks. Our research providing novel insights into clinical pathology of NGPV in ducks and providing a foundation for the research of NGPV treatment targeting gut microbiota.


Assuntos
Patos , Infecções por Parvoviridae , Filogenia , Doenças das Aves Domésticas , Animais , Patos/virologia , Infecções por Parvoviridae/veterinária , Infecções por Parvoviridae/virologia , Infecções por Parvoviridae/patologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/patologia , China , Parvovirinae/genética , Parvovirinae/isolamento & purificação , Parvovirinae/patogenicidade , Microbioma Gastrointestinal , Intestinos/patologia , Intestinos/virologia , RNA Ribossômico 16S/genética , Modelos Animais de Doenças , Disbiose/virologia , Disbiose/veterinária , Ácidos Graxos Voláteis/metabolismo , Gansos/virologia , Baço/patologia , Baço/virologia , Bico/virologia , Bico/patologia
18.
Food Chem ; 460(Pt 1): 140529, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39047468

RESUMO

In this work, a novel fluorinated magnetic microporous organic network (Fe3O4@FMON) was exquisitely designed and synthesized for highly efficient and selective magnetic solid phase extraction (MSPE) of fluorinated benzoylurea insecticides (BUs) from complex tea beverage samples. The Fe3O4@FMON exhibited good extraction for BUs via the pre-designed hydrophobic, π-π stacking, hydrogen bonding and specific FF interactions. A sensitive Fe3O4@FMON-based MSPE-HPLC-UV method with wide linear range (0.10-1000 µg L-1, R2 ≥ 0.996), low limits of detection (0.01-0.02 µg L-1), and large enrichment factors (85.6-98.0) for BUs from tea beverage samples was developed. By decorating F elements within MON's networks, the Fe3O4@FMON characterized good hydrophobicity and chemical stability, which could be reused at least 8 times without decrease of recoveries. This work demonstrated the great prospects of Fe3O4@FMON for enriching trace BUs from complex substrates and triggered the potential of FMON for sample pretreatment of fluorinated analytes.


Assuntos
Halogenação , Inseticidas , Extração em Fase Sólida , Chá , Inseticidas/química , Inseticidas/isolamento & purificação , Inseticidas/análise , Chá/química , Extração em Fase Sólida/métodos , Extração em Fase Sólida/instrumentação , Contaminação de Alimentos/análise , Adsorção , Porosidade , Cromatografia Líquida de Alta Pressão , Interações Hidrofóbicas e Hidrofílicas , Ureia/química , Ureia/isolamento & purificação
19.
Phytomedicine ; 130: 155785, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38823342

RESUMO

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.


Assuntos
Eritrócitos , Glicólise , Peróxido de Hidrogênio , Estresse Oxidativo , Panax , Ratos Sprague-Dawley , Saponinas , Tirosina , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Saponinas/farmacologia , Animais , Glicólise/efeitos dos fármacos , Tirosina/análogos & derivados , Tirosina/farmacologia , Tirosina/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Hemólise/efeitos dos fármacos , Antioxidantes/farmacologia , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Apoptose/efeitos dos fármacos
20.
Talanta ; 277: 126440, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38897013

RESUMO

Owing to their incomplete digestion in the human body and inadequate removal by sewage treatment plants, antiepileptic drugs (AEDs) accumulate in water bodies, potentially affecting the exposed humans and aquatic organisms. Therefore, sensitive and reliable detection methods must be urgently developed for monitoring trace AEDs in environmental water samples. Herein, a novel phenylboronic acid-functionalized magnetic cyclodextrin microporous organic network (Fe3O4@CD-MON-PBA) was designed and synthesized via the thiol-yne click post-modification strategy for selective and efficient magnetic solid-phase extraction (MSPE) of trace AEDs from complex sample matrices through the specific B-N coordination, π-π, hydrogen bonding, electrostatic, and host-guest interactions. Fe3O4@CD-MON-PBA exhibited a large surface area (118.5 m2 g-1), rapid magnetic responsiveness (38.6 emu g-1, 15 s), good stability and reusability (at least 8 times), and abundant binding sites for AEDs. Under optimal extraction conditions, the proposed Fe3O4@CD-MON-PBA-MSPE-HPLC-UV method exhibited a wide linear range (0.5-1000 µg L-1), low limits of detection (0.1-0.5 µg L-1) and quantitation (0.3-2 µg L-1), good anti-interference ability, and large enrichment factors (92.2-104.3 to 92.3-98.0) for four typical AEDs. This work confirmed the feasibility of the thiol-yne click post-synthesis strategy for constructing novel and efficient multifunctional magnetic CD-MONs for sample pretreatment and elucidated the significance of B-N coordination between PBA and N-containing AEDs.


Assuntos
Anticonvulsivantes , Ácidos Borônicos , Química Click , Ciclodextrinas , Extração em Fase Sólida , Compostos de Sulfidrila , Ácidos Borônicos/química , Anticonvulsivantes/química , Anticonvulsivantes/isolamento & purificação , Anticonvulsivantes/síntese química , Extração em Fase Sólida/métodos , Ciclodextrinas/química , Porosidade , Compostos de Sulfidrila/química , Alcinos/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , Limite de Detecção
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