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1.
J Hazard Mater ; 421: 126729, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34388920

RESUMO

Polysaccharide-based hydrogels offer a great overlook for environmental applications and help in the elimination of various noxious pollutants from the water system. Novel carrageenan and itaconic acid-based superadsorbent hydrogel having appreciable swelling properties and adsorption capacity towards Methylene blue (MB), Crystal violet (CV), and Methyl Red (MR) was synthesized by suspension polymerization technique. The swelling study showed the dependency upon the temperature in which the swelling rate increased with increasing temperature with a maximum swelling rate of 417% at 318 K. For ascertaining the maximum adsorption capacity, various influential parameters such as contact time, adsorbent dose, dye concentration, and temperature were systematically studied. Maximum adsorption capacity as calculated from the Langmuir isotherm was 2439.02, 1111.11, and 666.68 mg/g for MB, CV, and MR, respectively. Thermodynamic studies revealed the spontaneous nature of the undertaken dye adsorption experiment. Overall, the present study reveals that the synthesized superadsorbent hydrogel can be used as an efficient adsorbent for the removal of dyes from an aqueous solution.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Carragenina , Corantes , Hidrogéis , Concentração de Íons de Hidrogênio , Cinética , Azul de Metileno , Succinatos
2.
J Chromatogr A ; 1657: 462575, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34601254

RESUMO

This work reports a selective and inert triptycene-based stationary phase (TPT) combining the triptycene framework with tocopheryl polyethylene glycol succinate (TPGS) units for capillary gas chromatography (GC). The TPT stationary phase was physically coated onto a capillary column by static coating method with the column efficiency of 4200 plates/m and moderate polarity. As demonstrated, the TPT column exhibited high inertness towards organic bases, including basic heterocycles, aliphatic and aromatic amines, showing distinct advantages over the TPGS and commercial columns. Also, the TPT column displayed high-resolution performance towards the isomers of methylpyridines, toluidines, xylidines and alkanes (C6-C8). Moreover, it showed excellent separation repeatability and reproducibility with RSD values in the range of 0.03%-0.07% for run-to-run, 0.12%-0.18% for day-to-day and 2.3%-3.6% for column-to- column (n = 4). Its applications to purity test of chemical products and to GC-MS analysis of the essential oil of Artemisia annua L. demonstrated its good potential for practical analyses. The present work has novelty in constructing highly selective and inert stationary phases and providing a feasible strategy for concurrently addressing the related problems in GC analyses. Its methodology and findings is of important value in terms of fundamental researches and practical applications.


Assuntos
Fenóis , Polietilenoglicóis , Antracenos , Cromatografia Gasosa , Fenóis/análise , Reprodutibilidade dos Testes , Succinatos
3.
Comput Biol Med ; 137: 104817, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34488030

RESUMO

Microtubules have been widely studied in recent decades as an important pharmacological target for the treatment of cancer especially due to its key role in the mitosis process. Among the constituents of the microtubules, αß-tubulin dimers stand out in view of their four distinct interaction sites, including the so-called colchicine binding site (CBS) - a promising target for the development of new tubulin modulators. When compared to other tubulin sites, targeting the CBS is advantageous because this site is able to host ligands with lower molecular volume and lipophilicity, thus reducing the chances of entailing the phenomenon of multiple drug resistance (MDR) - one of the main reasons of failure in chemotherapy. However, colchicine, the first ligand ever discovered with affinity towards the CBS, despite modulating the action of microtubules, has shown toxicity in clinical studies. Therefore, in order to expand the known chemical space of scaffolds capable of interacting with CBS and to design non-toxic colchicine binding site inhibitors, we conducted a robust virtual screening pipeline. This has been rigorously validated and consisted of ligand- and structure-based methodologies, which allowed us to select four promising CBS inhibitors called tubLCQF1-4. These four compounds were also evaluated with long trajectories molecular dynamics simulations and respective results were used for the theoretical determination of the free energy released in the formation of the complexes, using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) methodology.


Assuntos
Colchicina , Simulação de Dinâmica Molecular , Adipatos , Sítios de Ligação , Simulação de Acoplamento Molecular , Succinatos , Moduladores de Tubulina/farmacologia
4.
FASEB J ; 35(10): e21936, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34547129

RESUMO

Lipopolysaccharide (LPS)-stimulated macrophages express an aconitate decarboxylase (IRG1, also called ACOD1), leading to accumulation of the endogenous metabolite itaconate. However, the precise mechanisms by which elevated itaconate levels alter macrophage function are not clear. Our hypothesis is itaconate affects macrophage function through some uncertain mechanism. Based on this, we established a transcriptional and proteomic signature of macrophages stimulated by itaconate and identified the pathways of IL-1ß secretion and altered iron metabolism. Consistently, the effect of IRG1 deficiency on IL-1ß secretion and iron metabolism was confirmed in IRG1 knockout THP-1 cell lines. Several common inhibitors and other compounds were used to examine the molecular mechanisms involved. Only cysteine and antioxidants (catechin hydrate) could inhibit caspase-1 activation and IL-1ß secretion in itaconate-stimulated macrophages. We further found that aconitase activity was decreased by itaconate stimulation. Our results demonstrate the counteracting effects of overexpression of mitochondrial aconitase (ACO2, a tricarboxylic acid cycle enzyme) or cytosolic aconitase (ACO1, an iron regulatory protein) on IL-1ß secretion and altered iron metabolism. Both enzyme activities were inhibited by itaconate because of iron-sulfur (Fe-S) cluster destruction. Our findings indicate that the immunoregulatory functions of IRG1 and itaconate in macrophages are stressful Fe-S cluster of aconitases disrupting and iron metabolism rebalancing.


Assuntos
Ferro/metabolismo , Macrófagos/metabolismo , Succinatos/metabolismo , Enxofre/metabolismo , Aconitato Hidratase/metabolismo , Carboxiliases/metabolismo , Linhagem Celular , Cisteína/metabolismo , Citocinas/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteoma/metabolismo , Proteômica
5.
Eur Heart J ; 42(42): 4386-4388, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34564722
6.
J Hazard Mater ; 416: 125714, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492774

RESUMO

In the present work, the removal of fast sulphon black (FSB) dye from water was executed by using chitin-cl-poly(itaconic acid-co-acrylamide)/zirconium tungstate nanocomposite hydrogel (Ch-cl-poly(IA-co-AAm)-ZrW NCH). The Ch-cl-poly(IA-co-AAm)-ZrW NCH was fabricated proficiently by microwave-induced sol-gel/copolymrization method. The zirconium tungstate (ZrW) photocatalyst was prepared by co-precipitation method using sodium tungstate and zirconium oxychloride in ratio (2:1). The polymeric hydrogel part has been used to support the ZrW, and it acted as an adsorbent for adsorptive removal of FSB dye. The band gap for nanocomposite hydrogel was found about 4.18 eV by using Tauc equation. The Ch-cl-poly(IA-co-AAm)-ZrW NCH was characterized by various techniques as FTIR (Fourier-transform infrared spectroscopy), X-ray diffraction (XRD), transmittance electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM). The adsorptional-photocatalytic remediation experiment of FSB dye was optimized for reaction parameters as FSB dye and Ch-cl-poly(IA-co-AAm)-ZrW NCH concentration, and pH. The maximum percentage removal for FSB dye was observed at 92.66% in 120 min under adsorptional-photocatalysis condition.


Assuntos
Quitina , Nanocompostos , Acrilamida , Concentração de Íons de Hidrogênio , Nanogéis , Espectroscopia de Infravermelho com Transformada de Fourier , Succinatos , Compostos de Tungstênio , Zircônio
7.
Adv Gerontol ; 34(3): 375-383, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34409816

RESUMO

Continuous improvement of protocols for the treatment of various ailments, in particular, osteochondrosis, is one of the important tasks of providing medical care to elderly patients. Supplementation of treatment with Cytoflavin and biofeed-back therapy seems to be a promising solution, however, it is necessary to develop an algorithm to predict it effectiveness in patients taking into account their initial clinical and psychophysiological status. As a result of the treatment, predictors of the effectiveness of the use of Cytoflavin and biofeed-back therapy have been identified and an algorithm for their administration has been developed.


Assuntos
Inosina Difosfato , Osteocondrose , Idoso , Algoritmos , Combinação de Medicamentos , Mononucleotídeo de Flavina , Humanos , Niacinamida , Succinatos , Resultado do Tratamento
8.
Front Cell Infect Microbiol ; 11: 730288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458164

RESUMO

The present study explores the SARS-CoV-2 drugable target inhibition efficacy of phytochemicals from Indian medicinal plants using molecular docking, molecular dynamics (MD) simulation, and MM-PBSA analysis. A total of 130 phytochemicals were screened against SARS-CoV-2 Spike (S)-protein, RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro). Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro targets with a docking score of -8.22, -6.86, and -9.73 kcal/mole, respectively. Further, MS 3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and Mpro targets respectively. The MD simulation was performed to study the favorable confirmation and energetically stable complex formation ability of Isoquercetin and 10-Hydroxyaloin A phytochemicals in Mpro-unbound/ligand bound/standard inhibitor bound system. The parameters such as RMSD, RMSF, Rg, SASA, Hydrogen-bond formation, energy landscape, principal component analysis showed that the lead phytochemicals form stable and energetically stabilized complex with the target protein. Further, MM-PBSA analysis was performed to compare the Gibbs free energy of the Mpro-ligand bound and standard inhibitor bound complexes. The analysis revealed that the His-41, Cys145, Met49, and Leu27 amino acid residues were majorly responsible for the lower free energy of the complex. Drug likeness and physiochemical properties of the test compounds showed satisfactory results. Taken together, the study concludes that that the Isoquercetin and 10-Hydroxyaloin A phytochemical possess significant efficacy to bind SARS-Cov-2 Mpro active site. The study necessitates further in vitro and in vivo experimental validation of these lead phytochemicals to assess their anti-SARS-CoV-2 potential.


Assuntos
COVID-19 , Simulação de Dinâmica Molecular , Adipatos , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2 , Succinatos
9.
Oxid Med Cell Longev ; 2021: 9932099, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457120

RESUMO

Oxidative stress, inflammation, and apoptosis are crucial in the pathogenesis of acute liver failure (ALF). 4-Octyl itaconate (OI) showed antioxidative and anti-inflammatory properties in many disease models. However, its role in lipopolysaccharide- (LPS-)/D-galactosamine- (D-GalN-) induced ALF is still not investigated. Here, we established an ALF murine model induced by LPS/D-GalN administration. And we found that OI improved survival rate in the murine ALF model. Our results also showed that OI alleviated LPS/D-GalN-induced hepatic histopathological injury and reduced the serum activities of alanine transaminase and aspartate transaminase. Moreover, OI reduced serum levels of proinflammatory cytokines such as monocyte chemotactic protein-1, tumor necrosis factors-α, and interlukin-6. Additionally, OI mitigated oxidative stress and alleviated lipid peroxidation in a murine model of ALF. This was evaluated by a reduction of thiobarbituric acid reactive substances (TBARS) in liver tissues. In addition, OI increased the ratio of reduced glutathione/oxidized glutathione and the activities of antioxidant enzymes including catalase and superoxide dismutase. Moreover, the apoptosis of hepatocytes in the liver was inhibited by OI. Furthermore, we found that OI inhibited LPS-induced nuclear translocation and activation of factor-kappa B (NF-κB) p65 in macrophages which could be inhibited by OI-induced activation of nuclear factor erythroid-2-related factor (Nrf2) signaling. Additionally, D-GalN-induced reactive oxygen species (ROS) generation and apoptosis in hepatocytes were inhibited by OI-induced activation of Nrf2 signaling. Therefore, the underlying mechanism for OI's protective effect in LPS/D-GalN-induced ALF may be associated with deactivation of NF-κB signaling in macrophages to reduce inflammation and inhibition of ROS-related hepatocyte apoptosis by activating Nrf2. In conclusion, OI showed a protective role in LPS/D-GalN-induced ALF by reducing inflammation, enhancing antioxidant capacity, and inhibiting cell apoptosis.


Assuntos
Apoptose , Galactosamina/toxicidade , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/tratamento farmacológico , Estresse Oxidativo , Succinatos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais
10.
Biomolecules ; 11(8)2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34439834

RESUMO

The glutarylation of lysine residues in proteins attracts attention as a possible mechanism of metabolic regulation, perturbed in pathologies. The visualization of protein glutarylation by antibodies specific to ε-glutaryl-lysine residues may be particularly useful to reveal pathogenic mutations in the relevant enzymes. We purified such antibodies from the rabbit antiserum, obtained after sequential immunization with two artificially glutarylated proteins, using affinity chromatography on ε-glutaryl-lysine-containing sorbents. Employing these anti(ε-glutaryl-lysine)-antibodies for the immunoblotting analysis of rat tissues and mitochondria has demonstrated the sample-specific patterns of protein glutarylation. The study of the protein glutarylation in rat tissue homogenates revealed a time-dependent fragmentation of glutarylated proteins in these preparations. The process may complicate the investigation of potential changes in the acylation level of specific protein bands when studying time-dependent effects of the acylation regulators. In the rat brain, the protein glutarylation, succinylation and acetylation patterns obtained upon the immunoblotting of the same sample with the corresponding antibodies are shown to differ. Specific combinations of molecular masses of major protein bands in the different acylation patterns confirm the selectivity of the anti(ε-glutaryl-lysine)-antibodies obtained in this work. Hence, our affinity-purified anti(ε-glutaryllysine)-antibodies provide an effective tool to characterize protein glutarylation, revealing its specific pattern, compared to acetylation and succinylation, in complex protein mixtures.


Assuntos
Glutaratos/metabolismo , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Succinatos/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Anticorpos/química , Anticorpos/isolamento & purificação , Especificidade de Anticorpos , Encéfalo/metabolismo , Cromatografia de Afinidade , Soros Imunes/química , Immunoblotting , Fígado/metabolismo , Masculino , Coelhos , Ratos
11.
Int J Mol Sci ; 22(16)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445761

RESUMO

Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate Rhodococcus sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.


Assuntos
Antivirais/metabolismo , Glicolipídeos/metabolismo , Rhodococcus/metabolismo , Animais , Antivirais/análise , Chlorocebus aethiops , Técnicas de Cultura , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres/metabolismo , Genoma Bacteriano , Glicolipídeos/química , Humanos , Metaboloma , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células PC-3 , Rhodococcus/química , Rhodococcus/genética , Succinatos/metabolismo , Tensoativos/química , Tensoativos/metabolismo , Células Vero
12.
Int J Pharm ; 607: 120979, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34371151

RESUMO

The aim of this investigation is to clarify the effect of D-α-tocopheryl succinate (vitamin E succinate, VES) and distearoylphosphatidyl ethanolamine-poly(ethylene glycol) (DSPE-PEG) on the encapsulation and controlled release of doxorubicin (DOX) in nano-assemblies and their consequences on the anti-tumor efficacy of DOX. DOX molecules were successfully loaded into the hybrid micelles with VES and DSPE-PEG (VDPM) via thin-film hydration method, exhibiting a small hydrodynamic particle size (~30 nm) and a weak negative zeta potential of around -5 mv. The obtained DOX-loaded VDPM2 displayed retarded DOX release at pH of 7.4, while substantially accelerated drug release at acidic pH of 5.0. Furthermore, the DOX-loaded VDPM2 exhibited substantially slower drug release rate at pH 7.4 compared with the drug-loaded VDPM1 or DPM preparation, benefiting for decreasing the premature DOX release during blood circulation. In vitro cell experiment indicated that DOX-loaded micelles (DPM, VDPM1 and VDPM2) improved the cellular uptake of DOX in 4T1 and MDA-MB-231 cells. The existence of VES component in the structure of DOX-loaded micelles had no obvious influence on the subcellular distribution of the encapsulated DOX molecules. Furthermore, the DOX-loaded VDPM2 exhibited more pronounced cytotoxicity to 4T1 and MDA-MB-231 cancerous cells compared with DOX-loaded DPM and free DOX solution. The hybrid nanocarriers including VES and DSPE-PEG selectively induced intracellular ROS accumulation and increased level of cytoplasmic calcium ion in cancerous cells by interacting with mitochondria and endoplasmic reticulum, bringing about the improved cytotoxicity of DOX. In vivo antitumor efficacy investigation of DOX-loaded VDPM2 against 4T1 xenograft-bearing mice displayed satisfied therapeutic activity with negligible systemic toxicity, as evidenced by the histological analysis and change of body weight. The proposed DOX-loaded VDPM preparation, as a mulifunctional chemotherapeutic nanomedicine system, holds great potential and bright prospect for clinical tumor therapy.


Assuntos
Micelas , alfa-Tocoferol , Animais , Linhagem Celular Tumoral , Doxorrubicina , Camundongos , Fosfolipídeos , Polietilenoglicóis , Succinatos
13.
AAPS PharmSciTech ; 22(7): 223, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34409520

RESUMO

D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) has shown potential applications in cancer therapy owing to its attractive properties, including reversal of multi-drug resistance and synergistic effects with antitumor drugs. However, its associated shortcomings cannot be underestimated, including activation of the body's immune response and acceleration of blood clearance of polyethylene glycolylated preparations. Polysialic acid (PSA) is a polysaccharide homopolymer, with the dual function of immune camouflage and tumor targeting. PSA and TPGS conjugates (PSA-TPGS) were synthesized to weaken the immune risks of TPGS. We developed PSA-TPGS and TPGS self-assembled mixed micelles and encapsulated the classical antineoplastic, docetaxel. The particle size of docetaxel-loaded mixed micelles was 16.3 ± 2.0 nm, with entrapment efficiency of 99.0 ± 0.9% and drug-loading efficiency of 3.20 ± 0.03%. Antitumor activity studies revealed that the mixed micelles showed better tumor inhibition than Tween 80 and TPGS micelles. Detection of the accelerated blood clearance (ABC) phenomenon demonstrated that insertion of PSA-TPGS into the micelles weakened the ABC phenomenon induced by TPGS. In summary, PSA-TPGS could be a potential nanocarrier to improve antitumor activity and weaken immune responses.


Assuntos
Antineoplásicos , Micelas , Antineoplásicos/farmacologia , Imunidade , Polietilenoglicóis , Ácidos Siálicos , Succinatos , Vitamina E
14.
Cells ; 10(8)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34440821

RESUMO

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that leads to skin fibrosis. Altered metabolism has recently been described in autoimmune diseases and SSc. Itaconate is a product of the Krebs cycle intermediate cis-aconitate and is an immunomodulator. This work examines the role of the cell-permeable derivative of itaconate, 4-octyl itaconate (4-OI), in SSc. SSc and healthy dermal fibroblasts were exposed to 4-OI. The levels of collagen Nrf2-target genes and pro-inflammatory cytokines interleukin 6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) were determined. Levels of reactive oxygen species (ROS) as well as the gene expression of collagen and Cellular Communication Network Factor 2 (CCN2) were measured after transforming growth factor beta 1 (TGF-ß1) stimulation in the presence or absence of 4-OI. Wild-type or Nrf2-knockout (Nrf2-KO) mouse embryonic fibroblasts (MEFs) were also treated with 4-OI to determine the role of Nrf2 in 4-OI-mediated effects. 4-OI reduced the levels of collagen in SSc dermal fibroblasts. Incubation with 4-OI led to activation of Nrf2 and its target genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). 4-OI activated antioxidant response element (ARE)-dependent gene expression, reduced inflammatory cytokine release and reduced TGF-ß1-induced collagen and ROS production in dermal fibroblasts. The effects of 4-OI are dependent on Nrf2. The cell-permeable derivative of itaconate 4-OI is anti-fibrotic through upregulation of Nrf2 and could be a potential therapeutic option in an intractable disease.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Escleroderma Sistêmico/patologia , Succinatos/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Elementos de Resposta Antioxidante/genética , Colágeno/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-6/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo , Escleroderma Sistêmico/metabolismo , Fator de Crescimento Transformador beta1/farmacologia
15.
Appl Microbiol Biotechnol ; 105(18): 6691-6706, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34463799

RESUMO

Natural water-soluble Monascus pigments (WSMPs) have been in increasing demand but have not been able to achieve industrial production due to the low production rate. This study aimed to improve the biosynthesis and secretion of extracellular yellow pigments (EYPs) through submerged fermentation with Monascus ruber CGMCC 10,910 supplemented with sodium starch octenyl succinate (OSA-SNa). The results demonstrated that the yield was 69.68% and 48.89% higher than that without OSA-SNa in conventional fermentation (CF) and extractive fermentation (EF), respectively. The mainly increased EYP components were Y3 and Y4 in CF, but they were mainly Y1 and Y2 as well as secreted intracellular pigments, including Y5, Y6, O1, and O2, in EF. Scanning electron microscopy analysis revealed that the mycelium presented an uneven surface profile with obvious wrinkles and small fragments with OSA-SNa. It was found that a higher unsaturated/saturated fatty acids ratio in the cell membrane resulted in increased permeability and facilitated the export of intracellular yellow pigments into the broth with OSA-SNa treatment. In addition, a higher NAD+/NADH ratio and glucose-6-phosphate dehydrogenase activity provided a reducing condition for yellow pigment biosynthesis. Gene expression analysis showed that the expression levels of the key genes for yellow pigment biosynthesis were significantly upregulated by OSA-SNa. This study provides an effective strategy to promote the production of WSMPs by microparticle-enhanced cultivation using OSA-SNa. KEY POINTS: • OSA-SNa addition facilitated the production of Monascus yellow pigments. • Mycelial morphology and membrane permeability were affected by OSA-SNa. • The key gene expression of yellow pigments was upregulated.


Assuntos
Monascus , Fermentação , Monascus/metabolismo , Pigmentos Biológicos/metabolismo , Sódio , Amido , Succinatos , Água
16.
J Food Sci ; 86(8): 3574-3588, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34287880

RESUMO

The objective of this study is to prepare zein/starch sodium octenyl succinate composite nanoparticles (ZSPs) via anti-solvent precipitation technology and characterize their colloidal properties. The effects of polar solvents, ultrasonic treatment time, and concentrations of starch sodium octenyl succinate were investigated. We measured the particle size distribution, hydrophobicity, and apparent structures of the composite nanoparticles. Ultrasonic treatment time (0-25 min) was found to play an important role in composite nanoparticle formation. The ZSP nanoparticles were with an average particle size in the range of 70 to 110 nm. When the ultrasonic treatment time exceeds 25 min, ZSPs became macroscopic particles. The fluorescence spectrum and three-phase contact angle indicated that ZSPs presented hydrophilicity with largest three-phase contact angle, which was 65.1°. Fourier transform infrared spectroscopy and scanning electron microscopy revealed that hydrophilic SSOS absorbed on the surface of zein nanoparticles via Van der Waals to improve their water solubility. The changes in solvent polarity and zein self-assembly are considered to be the main driving force for composite nanoparticles conformational transitions from α-helix to ß-sheet. Differential scanning calorimetry analysis indicated that ethanol combined ultrasonic treatment (10 min) was beneficial to enhance the thermal stability of composite nanoparticles, causing the highest Tg of 153.6°C. This work aims to provide a practical reference for formulating delivery systems using bioactive compounds containing zein as a carrier biopolymer. PRACTICAL APPLICATION: This work aims to provide a practical reference for formulating encapsulants for food and other bioactive compounds containing zein as a carrier biopolymer. Zein/starch sodium octenyl succinate composite nanoparticles formulated in this study provide novel stabilizers for emulsification systems or carriers of bioactive substances that can enhance the nutritional value, taste, or shelf life of foods.


Assuntos
Nanopartículas , Zeína , Etanol , Tamanho da Partícula , Sódio , Amido , Succinatos , Ultrassom
17.
Mol Med Rep ; 24(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34296312

RESUMO

The endogenous metabolite itaconate and its cell­permeable derivative dimethyl itaconate (DI) have been identified as anti­inflammatory regulators of macrophages; however, their contribution to inflammasome­mediated pyroptosis remains unknown. The present study examined the molecular mechanism of DI on NLR family pyrin domain­containing 3 (NLRP3) inflammasome assembly and NLRP3 inflammasome­dependent pyroptosis in microglia. Lipopolysaccharide (LPS) and ATP were used to induce microglia pyroptosis in vitro; this process was confirmed by TUNEL assay, lactate dehydrogenase (LDH) detection and gasdermin D (GSDMD) expression analysis. The regulation of microglia polarization and inflammatory cytokine expression was assessed by immunofluorescence assays and ELISA. To investigate the associated mechanism of action, the expression levels of the nuclear factor erythroid 2­related factor 2 (Nrf­2)/heme oxygenase­1 (HO­1) pathway proteins were analyzed by western blotting. Finally, the regulatory effect of DI on autophagy and its association with inflammation was determined by western blotting. The present study demonstrated that DI administration inhibited NLRP3 assembly, LDH release and GSDMD cleavage. Cotreatment of DI with LPS and ATP facilitated the transition from M1 to M2, reduced inflammatory mediator expression and impeded NF­κB phosphorylation. In addition, DI effectively reduced reactive oxygen species production through the Nrf­2/HO­1 pathway. Moreover, DI induced cellular autophagy, whereas inhibition of autophagy with 3­methyladenine markedly reversed its inhibitory effect on NLRP3­dependent pyroptosis. Taken together, the present study suggested that DI participated in the Nrf­2/HO­1 pathway and served a key role in microglia inflammation and NLRP3 inflammasome­mediated pyroptosis via induction of autophagy.


Assuntos
Heme Oxigenase-1/metabolismo , Inflamação/prevenção & controle , Proteínas de Membrana/metabolismo , Microglia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Piroptose/efeitos dos fármacos , Succinatos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Orig Life Evol Biosph ; 51(2): 87-116, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34251577

RESUMO

It has been proposed that clays could have served as key factors in promoting the increase in complexity of organic matter in primitive terrestrial and extraterrestrial environments. The aim of this work is to study the adsorption-desorption of two dicarboxylic acids, fumaric and succinic acids, onto clay minerals (sodium and iron montmorillonite). These two acids may have played a role in prebiotic chemistry, and in extant biochemistry, they constitute an important redox couple (e.g. in Krebs cycle) in extant biochemistry. Smectite clays might have played a key role in the origins of life. The effect of pH on sorption has been tested; the analysis was performed by UV-vis and FTIR-ATR spectroscopy, X-ray diffraction and X-ray fluorescence. The results show that chemisorption is the main responsible of the adsorption processes among the dicarboxylic acids and clays. The role of the ion, present in the clay, is fundamental in the adsorption processes of dicarboxylic acids. These ions (sodium and iron) were selected due to their relevance on the geochemical environments that possibly existed into the primitive Earth. Different mechanisms are proposed to explain the sorption of dicarboxylic acids in the clay. In this work, we propose the formation of complexes among metal cations in the clays and dicarboxylic acids. The organic complexes were probably formed in the prebiotic environments enabling chemical processes, prior to the appearance of life. Thus, the data presented here are relevant to the origin of life studies.


Assuntos
Bentonita , Succinatos , Adsorção , Silicatos de Alumínio , Cátions , Prebióticos
19.
J Mol Graph Model ; 107: 107969, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34237666

RESUMO

The ongoing COVID-19 pandemic demands a novel approach to combat and identify potential therapeutic targets. The SARS-CoV-2 infection causes a hyperimmune response followed by a spectrum of diseases. Limonoids are a class of triterpenoids known to prevent the release of IL-6, IL-15, IL-1α, IL-1ß via TNF and are also known to modulate PI3K/Akt/GSK-3ß, JNK1/2, MAPKp38, ERK1/2, and PI3K/Akt/mTOR signaling pathways and could help to avoid viral infection, persistence, and pathogenesis. The present study employs a computational approach of virtual screening and molecular dynamic (MD) simulations of such compounds against RNA-dependent RNA polymerase (RdRp), Main protease (Mpro), and Papain-like protease (PLpro) of SARS-CoV-2. MD simulation, Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA), and Essential dynamics revealed that the macromolecule-ligand complexes are stable with very low free energy of binding. Such compounds that could modulate both host responses and inhibit viral machinery could be beneficial in effectively controlling the global pandemic.


Assuntos
COVID-19 , Pandemias , Adipatos , Glicogênio Sintase Quinase 3 beta , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fosfatidilinositol 3-Quinases , SARS-CoV-2 , Succinatos
20.
Adv Gerontol ; 34(2): 306-310, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34245516

RESUMO

One of the ways to improve the condition of the elderly body is the method of auto-training with biofeedback, as a means of correcting deviations in the functioning of the regulatory apparatus, as well as improving antioxidant protection and eliminating the effects of oxidative stress using Cytoflavin therapy. These methods seem to be a simple and effective means of correcting negative changes in the FS of elderly hockey players after a training cycle and ensuring the possibility of a more complete recovery of their body. The difference in the points of application made it possible to combine the intake of Cytoflavin and biofeedback training into a single complex correctional and restorative technique. Purpose of the research: to consider the organizational and methodological aspects of introducing a comprehensive methodology for correcting the functional state of elderly hockey players into the system of support of their training process. Based on the results of the study, we have obtained convincing data on the positive effect of the inclusion of Cytoflavin and biofeedback training in the system of medical support for the training process of elderly hockey players. The organizational and methodological aspects of introducing a comprehensive methodology for correcting the functional state of older hockey players into the system of support for their training process considered in this article make it possible to solve a number of problems facing medical workers regarding continuous monitoring of the functional state of older hockey players, proactive diagnosis of their negative deviations, as well as a system of reabilitation.


Assuntos
Hóquei , Idoso , Antioxidantes , Combinação de Medicamentos , Mononucleotídeo de Flavina , Humanos , Inosina Difosfato , Niacinamida , Succinatos
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