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1.
Molecules ; 29(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611816

RESUMO

In this study, the α-glucosidase (maltase-glucoamylase: MGAM) and α-amylase inhibitory properties elicited by xylooligosaccharides (XOSs) prepared from dulse xylan were analysed as a potential mechanism to control postprandial hyperglycaemia for type-2 diabetes prevention and treatment. Xylan was purified from red alga dulse powder and used for enzymatic hydrolysis using Sucrase X to produce XOSs. Fractionation of XOSs produced xylobiose (X2), ß-(1→3)-xylosyl xylobiose (DX3), xylotriose (X3), ß-(1→3)-xylosyl-xylotriose (DX4), and a dulse XOS mixture with n ≥ 4 xylose units (DXM). The different fractions exhibited moderate MGAM (IC50 = 11.41-23.44 mg/mL) and α-amylase (IC50 = 18.07-53.04 mg/mL) inhibitory activity, which was lower than that of acarbose. Kinetics studies revealed that XOSs bound to the active site of carbohydrate digestive enzymes, limiting access to the substrate by competitive inhibition. A molecular docking analysis of XOSs with MGAM and α-amylase clearly showed moderate strength of interactions, both hydrogen bonds and non-bonded contacts, at the active site of the enzymes. Overall, XOSs from dulse could prevent postprandial hyperglycaemia as functional food by a usual and continuous consumption.


Assuntos
60578 , Glucuronatos , Hiperglicemia , Rodófitas , alfa-Amilases , Humanos , alfa-Glucosidases , Hipoglicemiantes/farmacologia , Xilanos/farmacologia , Simulação de Acoplamento Molecular , Oligossacarídeos/farmacologia
2.
Cell Death Dis ; 15(4): 267, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622131

RESUMO

Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a. The loss of HIF1a further leads to the inhibition of glycolysis in HCC cells. The activation of IDH1 by Scu can significantly increase the level of α-KG in tumor tissue, downregulate the HIF1a signaling pathway, and activate the tumor immune microenvironment in vivo. This study demonstrated the inhibitory effect of IDH1-α-KG-HIF1a on the growth of HCC cells and evaluated the inhibitory effect of Scu, the first IDH1 small molecule agonist, which provides a reference for cancer immunotherapy involving activated IDH1.


Assuntos
Carcinoma Hepatocelular , Glucuronatos , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteômica , Apigenina/farmacologia , Apigenina/uso terapêutico , Ácidos Cetoglutáricos/metabolismo , Microambiente Tumoral , Isocitrato Desidrogenase
3.
Riv Psichiatr ; 59(2): 52-59, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651773

RESUMO

INTRODUCTION: Prenatal alcohol exposure causes a variety of impairments to the fetus called Fetal Alcohol Spectrum Disorders (FASD). Since it is very difficult to identify women that consume alcohol during pregnancy, different methods have been studied to evaluate alcohol exposure. Ethyl Glucuronide (EtG) and Fatty Acid Ethyl Esters (FAEEs) are commonly used to measure alcohol consumption in individuals at-risk for alcohol abuse, including pregnant women. MATERIALS AND METHODS: We conducted a study of two cohorts of 1.5 year-old infants (of mothers without a history of alcohol abuse) with or without meconium samples positive to both EtG and FAEEs and we evaluated their cognitive-behavioral development by the Griffiths Mental Developmental Scale (GMDS) method. Our protocol included 8 infants with meconium positive to alcohol metabolites (EtG and FAEEs) and 7 with meconium negative to alcohol metabolites. RESULTS: None of the 8 alcohol metabolites positive meconium infants exhibited distinctive facial features and growth retardation of severe FASD, showing that other factors may contribute to the FASD onset but elevations in EtG and FAEEs in the meconium were significantly associated with disrupted neurodevelopment and adaptive functions within the first year and a half of life. Indeed, we found out that infants with meconium positive for both EtG and FAEEs, although without displaying any FASD morphological features, had a delay in the fine regulation of their own locomotory capabilities. CONCLUSIONS: Further analyses and larger studies are needed to estimate the right link between prenatal alcohol exposure and the different range of disorders connected but this study provides an additional step in the field of FASD in order to suggest early treatments for at-risk newborns and infants.


Assuntos
Biomarcadores , Transtornos do Espectro Alcoólico Fetal , Glucuronatos , Mecônio , Humanos , Mecônio/química , Mecônio/metabolismo , Projetos Piloto , Feminino , Transtornos do Espectro Alcoólico Fetal/metabolismo , Biomarcadores/metabolismo , Glucuronatos/análise , Lactente , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ácidos Graxos/metabolismo , Ácidos Graxos/análise , Consumo de Bebidas Alcoólicas/efeitos adversos , Recém-Nascido , Locomoção , Ésteres/análise , Desenvolvimento Infantil
4.
Traffic Inj Prev ; 25(4): 553-561, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497827

RESUMO

OBJECTIVE: The first aim of the study was to identify sex differences in the use of psychoactive substances among subjects with a previous driving under the influence (DUI) episode. The secondary objective was to propose specific strategies for medico-legal improvements. METHODS: This was a retrospective observational study that took place between June 1, 2019, and August 31, 2023. It was conducted on DUI subjects examined for reinstatement of their driver's license using an integrated medico-legal and toxicological approach. Ethyl glucuronide (EtG) and illicit psychoactive substances were determined from hair samples. We performed descriptive statistical analyses for the entire sample as well as separately by sex. Additionally, we conducted binary logistic regression analyses separately for males and females to identify protective/risk factors associated with previous road accidents and judgments of unfitness to drive due to excessive alcohol consumption (EtG ≥ 30 pg/mg). RESULTS: The study included 2,221 subjects, comprising 1,970 men and 251 women. Men exhibited a higher prevalence of tobacco, alcohol, and illicit psychoactive substance use. Women were more frequently co-users of alcohol and psychoactive substances and involved in road accidents at the time of DUI. Among the men, being married or having a partner was found to be a protective factor concerning past traffic accidents. For both sexes, a DUI episode with a blood alcohol concentration (BAC) exceeding 1.5 g/L or the co-ingestion of alcohol and drugs was identified as a risk factor for road accident involvement. For men, smoking more than 20 cigarettes per day and, for women, having a DUI episode with a BAC over 1.5 g/L were the main factors indicating unfitness to drive, as determined through high hair EtG levels (> 30 pg/mg). Women with a previous history of road accidents were less likely to have EtG levels of 30 pg/mg or more. CONCLUSIONS: The study confirmed sex differences in subjects with a previous DUI episode. A BAC exceeding 1.5 g/L or the simultaneous use of alcohol and drugs at the time of DUI necessitate careful assessment of both men and women seeking driver's license reinstatement. In women, a BAC exceeding 1.5 g/L is considered a risk factor for a subsequent judgment of unfitness to drive. The medico-legal assessment should also involve a thorough investigation of smoking habits in men, as these habits could be related to an increased risk of excessive alcohol consumption.


Assuntos
Condução de Veículo , Dirigir sob a Influência , Glucuronatos , Transtornos Relacionados ao Uso de Substâncias , Feminino , Humanos , Masculino , Acidentes de Trânsito , Concentração Alcoólica no Sangue , Etanol , Caracteres Sexuais , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estudos Retrospectivos
5.
Appl Environ Microbiol ; 90(4): e0222323, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38497645

RESUMO

An uncharacterized gene encoding a glycoside hydrolase family 43-like enzyme from Clostridium boliviensis strain E-1 was identified from genomic sequence data, and the encoded enzyme, CbE1Xyn43-l, was produced in Escherichia coli. CbE1Xyn43-l (52.9 kDa) is a two-domain endo-ß-xylanase consisting of a C-terminal CBM6 and a GH43-like catalytic domain. The positions of the catalytic dyad conserved in GH43, the catalytic base (Asp74), and proton donor (Glu240) were identified in alignments including GH43-enzymes of known 3D-structure from different subfamilies. CbE1Xyn43-l is active at pH 7.0-9.0, with optimum temperature at 65°C, and a more than 7 days' half-life in irreversible deactivation studies at this temperature. The enzyme hydrolyzed birchwood xylan, quinoa stalks glucuronoarabinoxylan, and wheat arabinoxylan with xylotriose and xylotetraose as major hydrolysis products. CbE1Xyn43-l also released xylobiose from pNPX2 with low turnover (kcat of 0.044 s-1) but was inactive on pNPX, showing that a degree of polymerization of three (DP3) was the smallest hydrolyzable substrate. Divalent ions affected the specific activity on xylan substrates, which dependent on the ion could be increased or decreased. In conclusion, CbE1Xyn43-l from C. boliviensis strain E-1 is the first characterized member of a large group of homologous hypothetical proteins annotated as GH43-like and is a thermostable endo-xylanase, producing xylooligosaccharides of high DP (xylotriose and xylotetraose) producer. IMPORTANCE: The genome of Clostridium boliviensis strain E-1 encodes a number of hypothetical enzymes, annotated as glycoside hydrolase-like but not classified in the Carbohydrate Active Enzyme Database (CAZy). A novel thermostable GH43-like enzyme is here characterized as an endo-ß-xylanase of interest in the production of prebiotic xylooligosaccharides (XOs) from different xylan sources. CbE1Xyn43-l is a two-domain enzyme composed of a catalytic GH43-l domain and a CBM6 domain, producing xylotriose as main XO product. The enzyme has homologs in many related Clostridium strains which may indicate a similar function and be a previously unknown type of endo-xylanase in this evolutionary lineage of microorganisms.


Assuntos
Glucuronatos , Glicosídeo Hidrolases , Oligossacarídeos , Xilanos , Xilanos/metabolismo , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Especificidade por Substrato , Clostridium/genética , Clostridium/metabolismo , Endo-1,4-beta-Xilanases/metabolismo , Hidrólise , Estabilidade Enzimática , Concentração de Íons de Hidrogênio
6.
Food Funct ; 15(6): 3122-3129, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38426554

RESUMO

Little is known regarding the effects of xylooligosaccharides (XOS) on insulin resistance (IR) in gestational diabetes mellitus (GDM). We aimed to investigate this issue and its mechanism. Sixty female mice were randomly allotted to 4 groups (n = 15): control, high fat diet (HFD), GDM, and GDM + XOS. The control mice were fed an AIN-93 diet, while the mice in the other groups were fed 45% HFD. After pregnancy, mice in GDM and GDM + XOS groups were intraperitoneally injected with 30 mg kg-1 streptozocin for 3 days from the first day of pregnancy. Mice in the GDM + XOS group were then fed an HFD containing 2% XOS. Fasting glucose and insulin levels were monitored. The fecal Akkermansia muciniphila (Akk. muciniphila) and Bifidobacterium were measured by qPCR. The Chiu scores were calculated from hematoxylin-eosin (HE)-stained ileal tissues. Phosphorylated Akt in the liver and occludin and ZO-1 in the intestinal tissues were determined by western blotting. XOS reduced (p < 0.05) fasting blood glucose and insulin and HOMA-IR, and increased (p < 0.05) Akt phosphorylation in the livers of GDM mice. Moreover, XOS decreased (p < 0.05) TNFα, IL-1ß, IL-15 and LPS in the serum, increased (p < 0.05) fecal Akk. muciniphila abundance, lowered (p < 0.05) Chiu's scores, and enhanced (p < 0.05) occludin and ZO-1 expression. XOS ameliorate IR by increasing Akk. muciniphila and improving intestinal barrier dysfunction in GDM mice.


Assuntos
Diabetes Gestacional , Gastroenteropatias , Glucuronatos , Resistência à Insulina , Enteropatias , Oligossacarídeos , Gravidez , Humanos , Feminino , Animais , Camundongos , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ocludina , Insulina , Akkermansia
7.
Bioresour Technol ; 398: 130526, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437967

RESUMO

Globally, the demands for sustainably sourced functional foods like prebiotic oligosaccharides have been constantly increasing. This study assessed the potential of pineapple leaves (PL) as lignocellulosic feedstock for sustainable production of cellulose and hemicellulose-derived oligosaccharides through its hydrothermal pretreatment (HT) followed by controlled enzymatic hydrolysis. PL was subjected to HT at 160, 175, and 190 °C for 20, 30, 60, and 90 min without any catalyst for xylooligosaccharide (XOS) production, whereas, the resulting solid content after HT was subjected to controlled enzymatic hydrolysis by commercial cellulase using conduritol B epoxide (0.5-5 mM) for glucooligosaccharides (GOS) production. HT at 160 °C for 60 min resulted in maximum yield of XOS and GOS at 23.7 and 18.3 %, respectively, in the liquid phase. Controlled enzymatic hydrolysis of HT treated (160 °C) PL solids for 20 and 30 min yielded âˆ¼ 174 mg cellobiose/g dry biomass within 24 h, indicating overall high oligosaccharide production.


Assuntos
Ananas , Celulose , Polissacarídeos , Hidrólise , Oligossacarídeos , Glucuronatos
8.
Clin Exp Pharmacol Physiol ; 51(4): e13845, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38382550

RESUMO

Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.


Assuntos
Apigenina , Aterosclerose , Glucuronatos , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células Espumosas/metabolismo , Células Espumosas/patologia , Músculo Liso Vascular/metabolismo , Ácido Oleico/farmacologia , Ácido Oleico/metabolismo , Aterosclerose/metabolismo , Autofagia , RNA Mensageiro/metabolismo , Miócitos de Músculo Liso/metabolismo
9.
Drug Alcohol Depend ; 257: 111128, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38394813

RESUMO

The increase in alcohol consumption in society has not only led to a number of medical issues but has also become a matter of considerable legal importance. Thus, there is both scientific interest and the necessity to diagnose alcohol abuse in the application of the provisions of the law through laboratory tests that ensure maximum objectivity. The purpose of this work is to study and compare the diagnostic performance of two of the main markers of alcohol abuse, serum carbohydrate-deficient transferrin (CDT) and Ethyl glucuronide (EtG) in a group of 336 driving under the influence (DUI) of alcohol offenders. Thus, it is possible to establish the best marker of alcohol consumption in order to assess the fitness to drive of DUI subjects.EtG was detected in 55 hair samples, while CDT was detected in 5 blood samples. Of the EtG-positive subjects 96,4% had CDT values below the cut-off. While CDT refers to an alcohol consumption of approximately the previous 10 days, EtG allows to detect an excessive alcohol consumption of the last few months. Because of these two different time-windows, EtG proves to be more reliable, since it is more difficult for subjects to change their drinking practice to test negative to toxicological analysis. The determination of Ethyl glucuronide on hair matrix is a valuable tool for the diagnosis of alcohol abuse, with high sensitivity and specificity and certainly greater reliability than traditional markers such as CDT, being a direct marker of alcohol consumption.


Assuntos
Alcoolismo , Transferrina/análogos & derivados , Humanos , Alcoolismo/diagnóstico , Reprodutibilidade dos Testes , Biomarcadores , Consumo de Bebidas Alcoólicas , Glucuronatos , Cabelo/química , Detecção do Abuso de Substâncias
10.
Sud Med Ekspert ; 67(1): 56-61, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38353016

RESUMO

Quantitative determination of ethyl glucuronide (EtG) in different biological objects in recent years has been positioned as one of the most reliable biomarkers of unconditional alcohol consumption. The aim of the study is to summarize the analytical methods of alcohol consumption testing with the use of EtG currently available in domestic and foreign literature and to present a schematic overview of possible errors in reproducibility and interpretation of research on EtG results, which may limit their use in forensic medical practice. The main objective is to increase the reliability and validity of EtG as a marker of ethanol consumption.


Assuntos
Consumo de Bebidas Alcoólicas , Detecção do Abuso de Substâncias , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias/métodos , Glucuronatos , Biomarcadores , Etanol
11.
Carbohydr Polym ; 331: 121869, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38388037

RESUMO

Xylooligosaccharides (XOS) have been employed as prebiotics containing oligomers of varying sizes or molecular ratios. XOS with a low degree of polymerization (DP) has been demonstrated to have high prebiotic potential. However, there is limited information regarding the specific chain length of XOS required to elicit distinct responses in the gut microbiota. In this study, we aimed to explore whether variations in XOS DP could alter the fate of colonic fermentation. Five XOS fractions (BWXFs) with DP ranges of >40, 20-40, 10-20, 5-10, and 2-4 were prepared by beechwood xylan autohydrolysis and tested on human gut microbiota. Extracellular XOS degradation was observed for molecules with a DP exceeding 5. BWXF treatments altered the microbial community structures, and substrate size-dependent effects on the microbial composition and metabolic outputs were observed. Bacteroidaceae were specifically enriched by xylan. Lachnospiraceae were particularly stimulated by XOS with a DP of 20-40 and 2-4. Bifidobacteriaceae were notably enriched by XOS with a DP of 5-20. High butyrate yields were obtained from cultures containing long-chain BWXFs. Microbiota responses differed with XOS DP composition changes, and microbial competition with XOS with a DP of 2-4 requires further exploration.


Assuntos
Prebióticos , Xilanos , Humanos , Fermentação , Xilanos/metabolismo , Colo/metabolismo , Oligossacarídeos/metabolismo , Glucuronatos/metabolismo
12.
Biotechnol Adv ; 72: 108319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38280495

RESUMO

The construction of high-performance microbial cell factories (MCFs) is the centerpiece of biomanufacturing. However, the complex metabolic regulatory network of microorganisms poses great challenges for the efficient design and construction of MCFs. The genome-scale metabolic network models (GSMs) can systematically simulate the metabolic regulation process of microorganisms in silico, providing effective guidance for the rapid design and construction of MCFs. In this review, we summarized the development status of 16 important industrial microbial GSMs, and further outline the technologies or methods that continuously promote high-quality GSMs construction from five aspects: I) Databases and modeling tools facilitate GSMs reconstruction; II) evolving gap-filling technologies; III) constraint-based model reconstruction; IV) advances in algorithms; and V) developed visualization tools. In addition, we also summarized the applications of GSMs in guiding metabolic engineering from four aspects: I) exploring and explaining metabolic features; II) predicting the effects of genetic perturbations on metabolism; III) predicting the optimal phenotype; IV) guiding cell factories construction in practical experiment. Finally, we discussed the development of GSMs, aiming to provide a reference for efficiently reconstructing GSMs and guiding metabolic engineering.


Assuntos
Dissacarídeos , Glucuronatos , Engenharia Metabólica , Redes e Vias Metabólicas , Engenharia Metabólica/métodos , Redes e Vias Metabólicas/genética , Fenótipo
13.
Bioresour Technol ; 395: 130398, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286168

RESUMO

The efficient utilization of biomass resources has gained widespread attention in current research. This study focused on the conversion of hemicellulose into xylo-oligosaccharides and furfural, as well as enhanced cellulose saccharification and lignin removal from residual biomass. The solid acid catalyst AT-Sn-MMT was prepared by sulfonation and tin ion loading of montmorillonite K-10. In a mixture of deep eutectic solvent and γ-valerolactone (3:7, v/v), AT-Sn-MMT was used to catalyze Phyllostachys edulis (PE) at 160 °C for 20 min, obtaining a furfural yield of 85.7 % and 1.5 g/L xylo-oligosaccharides. The delignification of pretreated PE was 59.5 %, reaching an accessibility of 221.3 g dye/g material. While the enzymatic saccharification efficiency was increased to 73.1 %. This work drew on the merits of solid acid catalysts and mixed solvent systems, and this constructed pretreatment method could be efficiently applied for co-production of reducing sugars, xylooligosaccharide and furfural, realizing the efficient valorization of PE.


Assuntos
Furaldeído , Glucuronatos , Açúcares , Solventes , Oligossacarídeos , Lignina , Poaceae , Biomassa , Hidrólise
14.
Org Biomol Chem ; 22(7): 1395-1399, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38291974

RESUMO

Herein we utilise automated glycan assembly to complete solid-phase synthesis of defined heparan sulfate oligosaccharides, employing challenging D-glucuronate disaccharide donors. Using an orthogonally protected D-GlcN-α-D-GlcA donor, milligram-scale synthesis of a heparan sulfate tetrasaccharide is completed in 18% yield over five steps. Furthermore, orthogonal protecting groups enabled regiospecific on-resin 6-O-sulfation. This methodology provides an important benchmark for the rapid assembly of biologically relevant heparan sulfate sequences.


Assuntos
Heparitina Sulfato , Oligossacarídeos , Dissacarídeos , Glucuronatos , Ácido Glucurônico
15.
J Stroke Cerebrovasc Dis ; 33(3): 107534, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219378

RESUMO

OBJECTIVE: The aim of this study was to investigate the effects of scutellarin on the activation of astrocytes into the A1 type following cerebral ischemia and to explore the underlying mechanism. METHODS: In vivo, a mouse middle cerebral artery wire embolism model was established to observe the regulation of astrocyte activation to A1 type by scutellarin, and the effects on neurological function and brain infarct volume. In vitro, primary astrocytes were cultured to establish an oxygen-glucose deprivation model, and the mRNA and protein expression of C3, a specific marker of A1-type astrocytes pretreated with scutellarin, were examined. The neurons were cultured in vitro to detect the toxic effects of ischemia-hypoxia-activated A1 astrocyte secretion products on neurons, and to observe whether scutellarin could reduce the neurotoxicity of A1 astrocytes. To validate the signaling pathway-related proteins regulated by scutellarin on C3 expression in astrocytes. RESULTS: The results showed that scutellarin treatment reduced the volume of cerebral infarcts and attenuated neurological deficits in mice caused by middle cerebral artery embolism. Immunofluorescence and Western blot showed that treatment with scutellarin down-regulated middle cerebral artery embolism and OGD/R up-regulated A1-type astrocyte marker C3. The secretory products of ischemia-hypoxia-activated A1-type astrocytes were toxic to neurons and induced an increase in neuronal apoptosis, and astrocytes treated with scutellarin reduced the toxic effects on neurons. Further study revealed that scutellarin inhibited the activation of NF-κB signaling pathway and thus inhibited the activation of astrocytes to A1 type.


Assuntos
Apigenina , Isquemia Encefálica , Embolia , Glucuronatos , AVC Isquêmico , Acidente Vascular Cerebral , Ratos , Camundongos , Animais , Astrócitos/metabolismo , AVC Isquêmico/metabolismo , Ratos Sprague-Dawley , Isquemia/metabolismo , Hipóxia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo
16.
Tissue Cell ; 87: 102300, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38211409

RESUMO

OBJECTIVE: Abnormal proliferation and migration of biomechanical force-induced venous smooth muscle cells (VSMCs) is a major cause to limit the efficacy of coronary artery bypass grafting (CABG) for coronary heart disease (CHD). Scutellarin is the main active ingredient of Erigeron Breviscapus, and has broad-spectrum pharmacological effects. Therefore, the present study was proposed to investigate the effect of Scutellarin on VSMCs under tensile stress. METHODS: After interfering with VSMCs at different tensile stresses, the optimal tensile stress was screened. In a tensile stress environment, 100 µM Scutellarin and Hesperetin (p38 MAPK pathway activator) was used to treatment with VSMCs. CCK-8, EDU, Wound healing, flow cytometry and western blotting assays were used to detect cell proliferation, migration, apoptosis, and the expression of apoptosis-related proteins (Caspase3, Bcl2 and Bax). RESULTS: Tensile stress with 10% significantly enhanced the activity, wound-healing ratio, and EDU+ cells of VSMCs, and decreased their apoptosis ratio. Moreover, it upregulated Bcl2 expression, and downregulated cleaved-Caspase3 and Bax expression of VSMCs. Hence, 10% tensile stress was selected to creates a tensile stress environment for VSMCs. Interestingly, 100 µM Scutellarin alleviated the effect of 10% tensile stress on the phenotype of VSMCs. Notably, 10% tensile stress increased the phosphorylation level of p38 MAPK (Thr180 +Tyr182) in VSMCs, which was restricted by Scutellarin. Further, Hesperetin restored the effect of Scutellarin on the phenotype of VSMCs. CONCLUSION: Scutellarin alleviates tension stress-induced proliferation and migration of VSMCs via suppressing p38 MAPK pathway. Scutellarin may be used as an adjunctive strategy for future GABG treatment in CHD patients.


Assuntos
Apigenina , Proteínas Reguladoras de Apoptose , Glucuronatos , Proteínas Quinases p38 Ativadas por Mitógeno , Humanos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteína X Associada a bcl-2/metabolismo , Células Cultivadas , Proliferação de Células , Proteínas Reguladoras de Apoptose/metabolismo , Miócitos de Músculo Liso , Movimento Celular/fisiologia
17.
Int J Biol Macromol ; 260(Pt 1): 129277, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38211918

RESUMO

GH 11 endo-ß-1,4-xylanase (Xy) was a crucial enzyme for xylooligosaccharides (XOS) production. The lower reusability and higher cost of purification has limited the industrial application of Xy. Addressing these challenges, our study utilized various immobilization techniques, different supports and forces for Xy immobilization. This study presents a new method in the development of Fe3O4@PDA@MOF-Xy which is immobilized via multi-point interaction forces, demonstrating a significant advancement in protein loading capacity (80.67 mg/g), and exhibiting remarkable tolerance to acidic and alkaline conditions. This method significantly improved Xy reusability and efficiency for industrial applications, maintaining 60 % activity over 10 cycles. Approximately 23 % XOS production was achieved by Fe3O4@PDA@MOF-Xy. Moreover, the yield of XOS from cobcorn xylan using this system was 1.15 times higher than that of the free enzyme system. These results provide a theoretical and applicative basis for enzyme immobilization and XOS industrial production.


Assuntos
Endo-1,4-beta-Xilanases , Oligossacarídeos , Endo-1,4-beta-Xilanases/metabolismo , Oligossacarídeos/metabolismo , Xilanos/metabolismo , Glucuronatos/metabolismo , Fenômenos Magnéticos , Hidrólise
18.
Food Funct ; 15(2): 894-905, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38168976

RESUMO

Xylooligosaccharides (XOSs) have recently garnered interest for their potential as an anti-constipation agent. In this study, we investigated the effects of XOSs derived from corn cobs on constipation in mice through a comprehensive analysis of both the metabolome and transcriptome. Our multi-omics approach revealed that XOSs primarily modulated butanoate metabolism and steroid hormone biosynthesis pathways, as well as key signaling pathways such as PPAR and NF-kappa B. Notably, we observed a decrease in inflammatory biomarker expression and an elevation of butyric acid metabolite levels with XOSs treatment. A deeper analysis of gene expression and metabolite alterations highlighted significant changes in genes encoding critical enzymes and metabolites involved in these pathways. Overall, these findings underscore the considerable potential of XOSs derived from corn cobs as a dietary supplement for effectively alleviating constipation.


Assuntos
Glucuronatos , Metabolômica , Oligossacarídeos , Zea mays , Camundongos , Animais , Zea mays/genética , Perfilação da Expressão Gênica , Transcriptoma , Metaboloma , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/genética
19.
Int J Biol Macromol ; 259(Pt 2): 129262, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199559

RESUMO

XOS production from lignocellulose using organic carboxylic acids and alkyd acids has been widely reported. However, it still faces harsh challenges such as high energy consumption, high cost, and low purity. Pyruvic acid (PYA), a carbonyl acid with carbonyl and carboxyl groups, was used to produce XOS due to its stronger catalytic activity. In this work, XOS was efficiently prepared from COS in an autoclave under the condition of 0.21 M PYA-121 °C-35 min. The total yield of XOS reached 68.72 % without producing any toxic by-products, including furfural (FF) and 5-hydroxymethylfurfural (5-HMF). The yield of xylobiose (X2), xylotriose (X3), xylotetraose (X4), and xylopentaose (X5) were 20.58 %, 12.47 %, 15.74 %, and 10.05 %, respectively. Meanwhile, 89.05 % of lignin was retained in the solid residue, which provides a crucial functional group for synthesizing layered carbon materials (SRG-a). It achieves excellent electromagnetic shielding (EMS) performance through graphitization, reaching -30 dB at a thickness of 2.0 mm. The use of a PYA catalyst in the production of XOS has proven to be an efficient method due to lower temperature, lower acid consumption, and straightforward operation.


Assuntos
Camellia , Ácido Pirúvico , Temperatura , Hidrólise , Oligossacarídeos/química , Glucuronatos/química , Ácidos
20.
Bioresour Technol ; 395: 130352, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272142

RESUMO

The productive separation and conversion of corn straw offers significant prospects for the economic viability of biorefineries centered on straw resources. In this work, a graded utilization method was proposed to produce xylo-oligosaccharides (XOS), ethanol and lignin from corn straw by nicotinic acid (NA) hydrolysis and water/pentanol pretreatment. A XOS yield of 52.6 % was achieved under optimized conditions of 100 mM NA, 170 °C and 30 min. The solid residue was directly treated with water/pentanol, achieving a lignin removal rate of 79.7 %, and the total XOS yield was improved to 62.6 %. The lignin recovered from pentanol had a high purity of 97.6 %, with high phenolic OH content. Simultaneous saccharification and fermentation of final residue resulted in an ethanol yield of 92.0 %, which yielded 55.3 g/L ethanol. Thus, NA hydrolysis and water/pentanol pretreatment provided an efficient, environmentally friendly approach to fractionate corn straw for the co-production of XOS, ethanol, and lignin.


Assuntos
Glucuronatos , Lignina , Niacina , Lignina/química , Zea mays , Etanol , Pentanóis , Hidrólise , Oligossacarídeos , Fermentação , Água
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