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1.
Methods Mol Biol ; 2519: 111-116, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36066716

RESUMEN

The standard FISH uses DNA probes to hybridize to the designated complementary strands. This is DNA-DNA interaction, and it usually takes much longer time to obtain detectable signals compared to other reactions such as immunochemical reactions and simple chemical reactions. Certain proteins bind to specific DNA sequences and regulate the biological function of DNA. These DNA-binding proteins have specific domains to interact with single- or double-stranded DNA. Some of telomere proteins apparently bind to telomere sequence and form nucleoprotein complex to protect chromosome ends. Using telomere PNA probes, probes can be accumulated at the telomere sites in a non-hybridization manner. This chapter introduces nontraditional PNA telomere staining protocol without DNA-DNA hybridization to visualize telomere locations on metaphase chromosomes.


Asunto(s)
Ácidos Nucleicos de Péptidos , Sondas de ADN/genética , Hibridación Fluorescente in Situ/métodos , Ácidos Nucleicos de Péptidos/química , Telómero/genética
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 287(Pt 1): 122059, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36410178

RESUMEN

The complex [Pt(AEP)Cl2]; C-1 (where, AEP = 1-(2-Aminoethyl) pyrrolidine) and its hydrolyzed diaqua form cis-[Pt(AEP)(H2O)2]2+; C-2 were synthesized for their bioactivity and in vitro kinetic study with bioactive thiol group (-SH) containing ligands (like; L- cysteine and N-ac-L- cysteine) for their biological importance for 'drug reservoir' activity. The Thermal Gravimetric Analysis (TGA) was executed to confirm about the weight loss due to coordinated water molecules at high temperature range. At pH 4.0, the substitution behavior of C-2 with the thiols was studied in pseudo-first order reaction condition. The interaction mechanism of thiols with complex C-2 to their corresponding thiol substituted C-3 [Pt(AEP)(L-cys)] and C-4 [Pt(AEP)(N-ac-L-cys)] (where L-cys = L-cysteine and N-ac-L-cys = N-ac-L- cysteine) were proposed from their thermodynamical activation parameters (ΔH≠ and ΔS≠), which were obtained from Eyring equation. DNA and BSA binding activity of the complexes C-1 to C-4 were investigated by gel electrophoresis technique, spectroscopic titration and viscosity methods. The binding activity of the complexes with DNA and BSA was evaluated using a theoretical approach molecular docking study. The drug-like nature of the complexes is supported by the prediction of activity spectra for substance (PASS) from 2D structure of the Pt(II) complexes. Structural optimization, HOMO-LUMO energy calculation, Molecular electrostatic potential surface, NBO and TD-DFT calculation were executed by using density functional theory (DFT) with Gaussian 09 software package to pre-assessment of biological activity of the complexes. DFT-based descriptors were determined from the HOMO-LUMA energy to be related with the ability of binding affinity of Pt(II) complexes towards DNA and BSA to the formation of their corresponding adducts. The anticancer property of the design complexes were examined on HCT116 (colorectal carcinoma) cancer cell lines and as well as human normal cell NKE (Normal Kidney Epithelial) and compared with the recognised anticancer drug cisplatin. The Reactive Oxygen Species (ROS) production was assessed by DCFDA assay in presence of the Pt(II) complexes.


Asunto(s)
Cisteína , ADN , Humanos , Simulación del Acoplamiento Molecular , Cinética , Pirrolidinas , Compuestos de Sulfhidrilo
3.
Carbohydr Polym ; 301(Pt B): 120347, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36446486

RESUMEN

Sulfobutylether ß-cyclodextrin (SBE-ß-CD) is a polyanionic cyclic oligosaccharide that contains glucopyranose units forming a torus ring-like structure. SBE-ß-CD is gifted with many favorable properties viz. relatively high solubility (>50 folds compared to ß-CD), improved stability, and biocompatibility that praised SBE-ß-CD as a smart polymer for drug delivery applications. Commercially, SBE-ß-CD is popular by its brand name Captisol®. The present review discusses the structure, properties, and preparation methods of SBE-ß-CD-based inclusion complexes (ICs). Furthermore, we discuss here the preparation and applications of SBE-ß-CD ICs-based nanoparticulate drug delivery systems, which combines the merits of both, ICs (enhanced solubility) and nanoparticles (NPs, targeted therapy). Patents on and FDA-approved Captisol®-enabled products are tabulated in the benefit of readers. The toxicological aspects and current clinical status of SBE-ß-CD or SBE-ß-CD-based products are briefly explained in the present review. In our opinion, the present review would be a pathfinder to allow dissemination of information on SBE-ß-CD.


Asunto(s)
Polímeros de Estímulo Receptivo , beta-Ciclodextrinas , Biopolímeros , Sistemas de Liberación de Medicamentos
4.
Water Res ; 228(Pt A): 119358, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36402058

RESUMEN

Antibiotic stewardship is hindered by a lack of consideration for complicated environmental fate of antibiotics and their role in resistance development, while the current methodology of eco-toxicological risk assessment has not been fully protective against their potential to select for antibiotic resistance. To address this problem, we established a novel methodologic framework to perform comprehensive environmental risk assessment of antibiotics in terms of resistance development, which was based on selection effect, phenotype resistance level, heteroresistance frequency, as well as prevalence and stability of antibiotic resistance genes. We tracked the contribution of antibiotic load reduction to the mitigation of environmental risk of resistance development by fate and transport modeling. The method was instantiated in a lake-river network-basin complex system, taking the Taihu Basin as a case study. Overall, antibiotic load posed no eco-toxicological risk but an average medium-level environmental risk for resistance development in Taihu Lake. The effect of antibiotic load on resistance risk was both seasonal-dependent and category-dependent, while quinolones posed the greatest environmental risk for resistance development. Mass-flow analysis indicated that temporal-spatial variation in hydrological regime and antibiotic fate together exerted a significant effect on antibiotic load in the system. By apportioning antibiotic load to riverine influx, we identified the hotspots for load reduction and predicted the beneficial response of resistance risk under load-reduction scenarios. Our study proposed a risk-oriented strategy of basin-scaled antibiotic load reduction for environmental risk control of resistance development.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Lagos , Ríos , Hidrología , Antibacterianos
5.
J Sci Food Agric ; 103(2): 820-828, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36038504

RESUMEN

BACKGROUND: Hsian-tsao gum (HG) has unique gel-promoting and nutritional properties; however, its use in processed foods is limited to starchy foods, partially due to a lack of knowledge related to its interaction with proteins. This study elucidated the interaction mechanism of heat-induced gelatin (G) (50 g kg-1 ) gel fortified with HG (0 ~ 20 g kg-1 ) using rheology, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), large deformation tests, low-field nuclear magnetic resonance (LF-NMR), and confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM). RESULTS: Heating promoted synergistic interactions between G and more HG molecules with enhanced apparent viscosity and higher storage modulus G' than loss modulus G″, thus shortening the gel time (tg ) of G-HG sols into gels. Fourier-transform infrared spectroscopy and DSC also confirmed the chemical interactions that occurred, facilitating the formation of ß-sheet structures of G. The microstructure of G gradually formed separate, coarse strands, and aggregated as HG was added, as observed by CLSM and SEM. This accelerated the gel formation rate and changed the textural properties. Although HG caused a disruptive decrease in the helix structure of G, it was possible to compensate for this by accelerating synergistic interactions, including depletion attractions and Maillard reactions, by heating. CONCLUSION: Hsian-tsao gum interacted synergistically with G as a result of heating and this accelerated the gel formation rate and improved the gel properties. Novel complex gels could be designed by blending HG to improve the gel properties of G in the heat processing of the food gel formulation. © 2022 Society of Chemical Industry.


Asunto(s)
Medicamentos Herbarios Chinos , Gelatina , Gelatina/química , Calor , Geles/química , Medicamentos Herbarios Chinos/química , Reología
6.
Biochim Biophys Acta Bioenerg ; 1864(1): 148930, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36272463

RESUMEN

At low inner mitochondrial membrane potential (ΔΨ) oxaloacetate (OAA) accumulates in the organelles concurrently with decreased complex II-energized respiration. This is consistent with ΔΨ-dependent OAA inhibition of succinate dehydrogenase. To assess the metabolic importance of this process, we tested the hypothesis that perturbing metabolic clearance of OAA in complex II-energized mitochondria would alter O2 flux and, further, that this would occur in both ΔΨ and tissue-dependent fashion. We carried out respiratory and metabolite studies in skeletal muscle and interscapular brown adipose tissue (IBAT) directed at the effect of OAA transamination to aspartate (catalyzed by the mitochondrial form of glutamic-oxaloacetic transaminase, Got2) on complex II-energized respiration. Addition of low amounts of glutamate to succinate-energized mitochondria at low ΔΨ increased complex II (succinate)-energized respiration in muscle but had little effect in IBAT mitochondria. The transaminase inhibitor, aminooxyacetic acid, increased OAA concentrations and impaired succinate-energized respiration in muscle but not IBAT mitochondria at low but not high ΔΨ. Immunoblotting revealed that Got2 expression was far greater in muscle than IBAT mitochondria. Because we incidentally observed metabolism of OAA to pyruvate in IBAT mitochondria, more so than in muscle mitochondria, we also examined the expression of mitochondrial oxaloacetate decarboxylase (ODX). ODX was detected only in IBAT mitochondria. In summary, at low but not high ΔΨ, mitochondrial transamination clears OAA preventing loss of complex II respiration: a process far more active in muscle than IBAT mitochondria. We also provide evidence that OAA decarboxylation clears OAA to pyruvate in IBAT mitochondria.

7.
Biochim Biophys Acta Bioenerg ; 1864(1): 148919, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36152681

RESUMEN

Formate hydrogenlyase-1 (FHL-1) is a complex-I-like enzyme that is commonly found in gram-negative bacteria. The enzyme comprises a peripheral arm and a membrane arm but is not involved in quinone reduction. Instead, FHL-1 couples formate oxidation to the reduction of protons to molecular hydrogen (H2). Escherichia coli produces FHL-1 under fermentative conditions where it serves to detoxify formic acid in the environment. The membrane biology and bioenergetics surrounding E. coli FHL-1 have long held fascination. Here, we review recent work on understanding the molecular basis of formic acid efflux and influx. We also consider the structure and function of E. coli FHL-1, its relationship with formate transport, and pay particular attention to the molecular interface between the peripheral arm and the membrane arm. Finally, we highlight the interesting phenotype of genetic mutation of the ND1 Loop, which is located at that interface.

8.
Biosens Bioelectron ; 220: 114839, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36327903

RESUMEN

Development of simple, low-cost and highly sensitive electrochemiluminescence (ECL) sensors for various targets is urgent but remains challenging. It is because most of emitters were required to be dissolved in organic solvent or immobilized at electrode's surface to display ECL emission, and suffered from complicated tagging procedures and short emission wavelength. Herein, we synthesize an iridium (III) complex (Ir-ECL) and applied it as a ECL emitter for improved target sensing. ECL emission of Ir-ECL originated from the sensitization of N-heterocyclic ligands on Ir (III). Impressively, Ir-ECL exhibited ECL emission wavelength at 590 nm, and displayed a superior intercalation ability into G-quadruplex DNA against single-stranded DNA and double-stranded DNA (dsDNA). Using such properties, Ir-ECL was applied to enzyme-free, label-free, sensitive and homogeneous ECL analysis of pesticide acetamiprid (Ace) based on aptamer-target recognition-driven hybridization chain reaction (HCR). The recognition of H1 by Ace switched HCR of H2 and H3 to generate a long-chain dsDNA with abundant G-quadruplex DNAs, in which large numbers of Ir-ECL were locked, resulting in falling diffusion toward electrode, declining ECL signal and eventually improving Ace ECL sensing.


Asunto(s)
Técnicas Biosensibles , G-Cuádruplex , Iridio , Técnicas Biosensibles/métodos , Mediciones Luminiscentes/métodos , Hibridación de Ácido Nucleico/métodos , ADN/química , Técnicas Electroquímicas/métodos
9.
Biosens Bioelectron ; 220: 114828, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36327905

RESUMEN

MicroRNAs (miRNAs) play an important role in post-transcriptional regulation of gene expression. However, methods to accurately detect miRNA activity in living cells are still limited. Here we developed a DNA nanomachine initiated by a miRNA-induced silencing complex (miRISC) for imaging miRNA activity in living cells. miRISC-mediated RNA cleavage reaction activated the DNA nanomachine by the specific cleavage of an RNA strand on the machine, resulting in autonomous movement of the walking leg around the AuNP surface with the release of a large number of fluorescently labeled DNA strands. The DNA nanomachine was successfully applied to detect miR-21 activity in three cell lines with different miR-21 expression profiles. We also demonstrated that terminal uridylyltransferase Tut4 knockdown by siRNA significantly increased the activity of let-7b miRNA, which further verifies the versatility of our DNA nanomachine. This new nanomachine has distinct advantages compared with reported methods for detecting miRNA activity, including simple operating procedures, short analysis time and sensitive signal output. Collectively, this work not only expands the application of the DNA nanomachine in the detection of miRNA activity, but also provides a promising tool for basic research in cell biology and development of clinical biomedicine.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , MicroARNs , MicroARNs/análisis , Técnicas Biosensibles/métodos , ADN/genética , Línea Celular
10.
Blood Cells Mol Dis ; 98: 102708, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36334505

RESUMEN

Severe aplastic anemia (SAA) is a bone marrow failure disorder caused by autoimmune dysfunction. The presentation by dendritic cells (DCs) is the key step in initiating the immune response against unknown antigens in SAA patients. In the previous phase, we found that compared to healthy controls, patients with SAA had an increased proportion of circulating myeloid/conventional dendritic cells (mDCs/cDCs) with enhanced phagocytosis, more secretion of Th1-type cytokines (IL-2, TNF-α, IFN-γ) in the bone marrow, and a reduced proportion of Treg cells. In this study, we found that cDCs sorted from SAA patients had higher expression level of HLA-DQ, co-stimulatory molecules CD86, PTK and ERK1/2 than the remission SAA patients and healthy controls. Moreover, downregulation of HLA-DQ protein levels on cDCs derived from SAA patients resulted in reduced phagocytosis rate and CD86 expression of cDCs. When the cDCs above were co-cultured with CD4+ cells from the same patients, reduced secretion of Th1 type of lymphocyte cytokines was observed. Analysis of clinically relevant data suggests that HLA-DQ expression levels were closely related to disease severity and immune status of patients. These findings show that the role of HLA-DQ in the immunopathogenesis of SAA is potentially important and worth further study.


Asunto(s)
Anemia Aplásica , Humanos , Médula Ósea/patología , Factor de Necrosis Tumoral alfa , Antígenos HLA-DQ/metabolismo
11.
Bioorg Chem ; 130: 106234, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36375353

RESUMEN

Ras protein has been considered a fascinating target for anticancer therapy because its malfunction is closely related to cancer. However, Ras has been considered undruggable because of the failure to regulate its malfunction by controlling the Ras activation mechanism. Recently, Lumakras targeting the G12C mutation was approved, and therapeutic interest in Ras for anticancer therapy has been rejuvenated. Here, we present a series of compounds that inhibit Ras via a unique mechanism of action that exploits the relationship between the Wnt/ß-catenin pathway and Ras. KYA1797K (1) binds to axin to stabilize the ß-catenin destruction complex that causes the phosphorylation and subsequent degradation of Ras, similar to canonical ß-catenin regulation. Based on the chemical structure of 1, we performed a structural optimization and identified 3-(2-hydroxyethyl)-5-((6-(4-nitrophenyl)pyridin-2-yl)methylene)thiazolidine-2,4-dione (13d) as the most potent compound. 13d displayed antitumor effects in a colorectal cancer model with enhanced inhibition activity on Ras. The results of this study suggest that the further development of 13d could contribute to the development of Ras inhibitors with novel mechanisms of action.


Asunto(s)
Neoplasias Colorrectales , beta Catenina , Humanos , beta Catenina/química , Proteína Axina/química , Proteína Axina/genética , Proteína Axina/metabolismo , Vía de Señalización Wnt , Proteínas ras/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología
12.
Philos Trans R Soc Lond B Biol Sci ; 378(1868): 20210437, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36440558

RESUMEN

Helping behaviour is thought to play a major role in the evolution of group-living animals. Yet, it is unclear to what extent human males and human females use the same strategies to secure support. Accordingly, we investigate help-seeking over a 5-year period in relation to gender using data from virtually all adults in two Tamil villages (N = 782). Simulations of network dynamics (i.e. stochastic actor-oriented models) calibrated to these data broadly indicate that women are more inclined than men to create and maintain supportive bonds via multiple mechanisms of cooperation (e.g. reciprocity, kin bias, friend bias, generalized exchange). However, gender-related differences in the simulated dynamics of help-seeking are modest, vary based on structural position (e.g. out-degree), and do not appear to translate to divergence in the observed structure of respondents' egocentric networks. Findings ultimately suggest that men and women in the two villages are similarly social but channel their sociality differently. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.


Asunto(s)
Conducta de Ayuda , Red Social , Masculino , Adulto , Animales , Humanos , Femenino , India , Factores Sexuales
13.
MAbs ; 15(1): 2149055, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36458900

RESUMEN

Nerve growth factor (NGF) has emerged as a key driver of pain perception in several chronic pain conditions, including osteoarthritis (OA), and plays an important role in the generation and survival of neurons. Although anti-NGF antibodies improve pain control and physical function in patients with clinical chronic pain conditions, anti-NGF IgGs are associated with safety concerns such as effects on fetal and postnatal development and the risk of rapidly progressive osteoarthritis. To overcome these drawbacks, we generated a novel anti-NGF PEGylated Fab' antibody. The anti-NGF PEGylated Fab' showed specific binding to and biological inhibitory activity against NGF, and analgesic effects in adjuvant-induced arthritis model mice in a similar manner to an anti-NGF IgG. In collagen-induced arthritis model mice, the anti-NGF PEGylated Fab' showed higher accumulation in inflamed foot pads than the anti-NGF IgG. In pregnant rats and non-human primates, the anti-NGF PEGylated Fab' was undetectable in fetuses, while the anti-NGF IgG was detected and caused abnormal postnatal development. The PEGylated Fab' and IgG also differed in their ability to form immune complexes in vitro. Additionally, while both PEGylated Fab' and IgG showed analgesic effects in sodium monoiodoacetate-induced arthritic model rats, their effects on edema were surprisingly quite different. While the anti-NGF IgG promoted edema over time, the anti-NGF PEGylated Fab' did not. The anti-NGF PEGylated Fab' (ASP6294) may thus be a potential therapeutic candidate with lower risk of adverse effects for various diseases in which NGF is involved such as OA and chronic back pain.


Asunto(s)
Analgesia , Artritis Experimental , Dolor Crónico , Osteoartritis , Femenino , Embarazo , Ratas , Ratones , Animales , Dolor Crónico/tratamiento farmacológico , Artritis Experimental/tratamiento farmacológico , Analgésicos , Polietilenglicoles/efectos adversos , Inmunoglobulina G
14.
J Mol Graph Model ; 118: 108347, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36208591

RESUMEN

Cytochrome b (QcrB) is considered an essential subunit in the electron transport chain that coordinates the action of the entire cytochrome bc1 oxidase. It has been identified as an attractive drug target for a new promising clinical candidate Q203 that depletes the intracellular ATP levels in the bacterium, Mycobacterium tuberculosis. However, single point polymorphism (T313A/I) near the quinol oxidation site of QcrB developed resistance to Q203. In the present study, we analyze the structural changes and drug-resistance mechanism of QcrB due to the point mutation in detail through conformational morphing and molecular docking studies. By morphing, we generated conformers between the open and closed state of the electron transporting cytochrome bc1-aa3 super complex. We clustered them to identify four intermediate structures and relevant intra- and intermolecular motions that may be of functional relevance, especially the binding of Q203 in wild and mutant QcrB intermediate structures and their alteration in developing drug resistance. The difference in the binding score and hydrogen bond interactions between Q203 and the wild-type and mutant intermediate structures of QcrB from molecular docking studies showed that the point mutation T313A severely affected the binding affinity of the candidate drug. Together, the findings provide an in-depth understanding of QcrB inhibition in different conformations, including closed, intermediate, and open states of cytochrome bc1-aa3 super complex in Mycobacterium tuberculosis at the atomic level. We also obtain insights for designing QcrB and cytochrome bc1-aa3 inhibitors as potential therapeutics that may combat drug resistance in tuberculosis.


Asunto(s)
Complejo III de Transporte de Electrones , Mycobacterium tuberculosis , Complejo III de Transporte de Electrones/genética , Complejo III de Transporte de Electrones/metabolismo , Ligandos , Simulación del Acoplamiento Molecular , Mycobacterium tuberculosis/genética , Análisis por Conglomerados
15.
Magn Reson Med ; 89(2): 812-827, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36226661

RESUMEN

PURPOSE: To evaluate an iterative learning approach for enhanced performance of robust artificial-neural-networks for k-space interpolation (RAKI), when only a limited amount of training data (auto-calibration signals [ACS]) are available for accelerated standard 2D imaging. METHODS: In a first step, the RAKI model was tailored for the case of limited training data amount. In the iterative learning approach (termed iterative RAKI [iRAKI]), the tailored RAKI model is initially trained using original and augmented ACS obtained from a linear parallel imaging reconstruction. Subsequently, the RAKI convolution filters are refined iteratively using original and augmented ACS extracted from the previous RAKI reconstruction. Evaluation was carried out on 200 retrospectively undersampled in vivo datasets from the fastMRI neuro database with different contrast settings. RESULTS: For limited training data (18 and 22 ACS lines for R = 4 and R = 5, respectively), iRAKI outperforms standard RAKI by reducing residual artifacts and yields better noise suppression when compared to standard parallel imaging, underlined by quantitative reconstruction quality metrics. Additionally, iRAKI shows better performance than both GRAPPA and standard RAKI in case of pre-scan calibration with varying contrast between training- and undersampled data. CONCLUSION: RAKI benefits from the iterative learning approach, which preserves the noise suppression feature, but requires less original training data for the accurate reconstruction of standard 2D images thereby improving net acceleration.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Algoritmos , Estudios Retrospectivos , Redes Neurales de la Computación
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 287(Pt 1): 122045, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36327811

RESUMEN

A paper-based colourimetric assay for the Point-of-Care Testing (PoCT) of bilirubin has been developed based on the formation of a green-coloured copper-bilirubin complex from a blue-coloured tetraamminecopper(II) sulphate complex. The reaction was studied and optimized by UV-Visible absorption spectroscopy and translated onto a paper strip. Hydrophobic circular well patterns on Whatman chromatography paper were created by wax printing. The tetraamminecopper(II) sulphate complex was drop cast and dried on the reagent zones in the wax-patterned paper. The images of reagent zones captured using a scanner were analyzed using ImageJ software. Bilirubin spiked blood serum was tested in the concentration range of 1.2 to 950 µM. The PAD exhibited sensitivities of 0.4197 a.u/µM and 0.1040 a.u/µM for concentration ranges of bilirubin 1.2 to 96 µM and 105 to 950 µM respectively and a low detection limit of 0.799 µM. The method is highly selective to bilirubin, even in the presence of other biomarkers in serum. A plasma separation membrane incorporated PAD was fabricated for the final testing and quantification of bilirubin from whole blood.


Asunto(s)
Colorimetría , Papel , Bilirrubina , Pruebas en el Punto de Atención , Sulfatos
17.
Phytomedicine ; 108: 154523, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36332385

RESUMEN

BACKGROUND: Chronic and persistent obesity can lead to various complications, including obesity cardiomyopathy. Inhibition of the inflammatory response is an effective measure for the intervention of obesity cardiomyopathy. Numerous studies indicate that costunolide (Cos) can reduce inflammation. However, the role of Cos in obesity cardiomyopathy and its molecular targets remains unknown. HYPOTHESIS/PURPOSE: We aimed to clarify potential cardioprotective effects and mechanism of Cos against obesity cardiomyopathy. METHODS: The model of obesity cardiomyopathy was established by feeding mice with a high-fat diet for 24 weeks. Cos at 10 and 20 mg/kg or vehicle (1% CMCNa solution) was administered once every two days via oral gavage from the 17th to 24th week. Body weight, heart weight/tibia length, cardiac function, myocardial injury markers, pathological morphology of the heart, hypertrophic and fibrotic markers, inflammatory factors were assessed. The targets of Cos were predicted through molecular docking. Pull-down assay and biolayer interferometry were used to confirm the target of Cos. RESULTS: Cos effectively reduces obesity-induced cardiomyocyte inflammation, cardiac hypertrophy and fibrosis, thereby improving cardiac function. We confirmed that Cos can interact with TAK1 and inhibit downstream NF-κB pathway activation by blocking the formation of the TAK1/TAB2 complex, thus inhibiting inflammatory cytokine release in cardiomyocytes. CONCLUSION: Our results demonstrated that Cos significantly improved myocardial remodeling and cardiac dysfunction against obesity cardiomyopathy by reducing myocardial inflammation. Therefore, Cos may serve as a promising therapeutic agent in obesity cardiomyopathy.


Asunto(s)
Cardiomiopatías , FN-kappa B , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Inflamación/patología , Quinasas Quinasa Quinasa PAM/metabolismo , Simulación del Acoplamiento Molecular , Miocitos Cardíacos/metabolismo , FN-kappa B/metabolismo , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Transducción de Señal
18.
J Environ Manage ; 326(Pt B): 116849, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36435129

RESUMEN

Understanding homeowners' energy-efficiency retrofit (EER) decision-making is a critical priority for reducing the adverse environmental impacts of the building sector and promoting a sustainable consumption transition. Existing research lacks attention to the dynamics and social interactions in the decision-making process of homeowner EER adoption. This paper applies the complex network-based evolutionary game approach with agent-based modeling to construct an evolutionary dynamics model for homeowners' EER adoption decision-making. Through simulation experiments, this paper examines the effects of various key factors, including government incentives, retrofit costs, retrofit uncertainty, and network size, on the evolution of EER adoption. The results suggest that government incentives facilitate EER adoption, but their effects require a sufficiently long period of policy implementation and extensive social interaction to be realized. Reducing retrofit costs is a robust and effective way to encourage EER adoption, especially when uncertainty is high. Retrofit uncertainty has a significant impact on the adoption evolution. Increased uncertainty can hinder adoption decisions. In particular, the combination of high uncertainty and incentives is prone to lead to incentive failure. The increase in network size contributes to EER adoption, but attention needs to be paid to the impact of potential incentive redundancy in large-scale networks.

19.
Food Chem ; 405(Pt B): 134971, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36436236

RESUMEN

Gracilaria lemaneiformis is a source of several bioactive natural products in China. Previously, we obtained Saccharomyces cerevisiae JJ4 and Lactobacillus paracasei paracasei RP38, that reduced the fishy odor of G. lemaneiformis. However, the associated deodorization mechanisms remain unclear. Here, G. lemaneiformis was fermented using single strain JJ4, single strain RP38, and both strains together. Dynamic changes in volatile aroma substances during fermentation were measured using HS-SPME-GC/MS. We found that the unpleasant aromas of raw G. lemaneiformis were primarily due to 3-octanone, cyclooctanol, and 1-methylcycloheptanol. Fermentation with lactic acid bacteria and yeast could reduce the substances associated with unpleasant aromas. The potentially characteristic aromatic substances consumed and produced by the different strains were determined using Opls-da and Spearman's correlations with VIP value >1 and |r| > 0.6. These results help to clarify the metabolic mechanisms by which different microbes reduce the fishy smell of G. lemaneiformis.


Asunto(s)
Gracilaria , Lactobacillales , Saccharomyces cerevisiae , Odorantes , Fermentación
20.
J Inorg Biochem ; 238: 112057, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36370504

RESUMEN

It is a major challenge to design novel multifunctional metal-based chemotherapeutic agents for anti-tumor and anti-metastasis applications. Two complexes (OA-Ir and OA-Ru) were synthesized via CuAAC (copper-catalyzed azide-alkyne cycloaddition) reaction from nontoxic Ir-N3 or Ru-N3 species and low toxic alkynyl precursor OA-Alkyne, and exhibited satisfactory anti-tumor and anti-metastasis pharmacological effects. Conjugation of Oleanolic acid (OA) and metal-arene species significantly enhanced the cytotoxicity in A2780 cells compared to the precursors through mitochondrial-induced autophagy pathway. Moreover, the two complexes could inhibit the cell metastasis and invasion through damage of actin dynamics and down-regulation of MMP2/MMP9 proteins. Combination of two precursors improved the lipophilicity and biocompatibility, simultaneously enhanced the cell uptake and the mitochondrial accumulation of metal-arene complexes, which caused mitochondrial membrane potential damage, oxidative phosphorylation, ATP depletion and autophagy. Besides, OA-Ir and OA-Ru displayed excellent activity to disintegrate the 3D multicellular tumor spheroids, showing potential for the treatment of solid tumors. This work provides a new way for developing novel metal-based complexes via CuAAC reaction for simultaneously inhibiting tumor proliferation and metastasis.


Asunto(s)
Complejos de Coordinación , Neoplasias Ováricas , Rutenio , Humanos , Femenino , Rutenio/farmacología , Iridio/farmacología , Línea Celular Tumoral , Complejos de Coordinación/farmacología , Alquinos
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