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1.
Food Chem ; 398: 133858, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964569

RESUMO

This work investigated the isomerization of galactose to tagatose, a low caloric rare sugar, using arginine as a catalyst. Galactose (5 % w/v) and arginine (0.10 mol/mol-galactose) in water were treated at 90-120 °C. The results showed that as the temperature and time increased, galactose was continuously consumed. Rare sugars namely tagatose, talose, and sorbose were formed with the highest yield of 16.8, 2.7, and 3.3 %, respectively at 120 °C, 20 min. High temperature and short time conditions resulted in lower Maillard reaction extent. The arginine concentrations at 0.05, 0.10, and 0.15 mol/mol-galactose resulted in a slight increase in tagatose yield while an increase of the initial galactose concentration from 5 to 20 % resulted in a decrease in tagatose yield, although the tagatose concentration increased. The highest tagatose productivity of 278 g/(L⋅h) was obtained using galactose of 20 % w/v and arginine of 0.10 mol/mol-galactose at 120 °C and 4 min.


Assuntos
Arginina , Galactose , Hexoses , Isomerismo
2.
Food Chem ; 398: 133905, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35969991

RESUMO

Maillard reaction products (MRPs) play pivotal roles in gut health by affecting the microbiome-host interactions. This study aimed at investigating the effects of MRPs derived from bighead carp meat hydrolysates with galactose and galacto-oligosaccharides on intestinal microbial composition and metabolic profile by in vitro pig fecal fermentation. The pH decreased sharply in the first 12 h and the highest production of butyric acid was observed in GM (glycated BCH with galacto-oligosaccharide) treatment with 64.7 µmoL/10 mL (p < 0.05) at 48 h. Clostridium_sensu_stricto_1, Streptococcus, and Enterococcus were dominant in the GM treatment, while Escherichia-Shigella was predominant in LgM (glycated BCH with galactose) treatment at 12 h. The up-regulated metabolites indicated that GM and LgM might participate in the fatty acids synthesis and modulate lipid metabolism, respectively. Overall, GM will be more beneficial for gut health by promoting the production of butyric acid and fatty acids synthesis.


Assuntos
Carpas , Microbioma Gastrointestinal , Animais , Ácido Butírico , Carpas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fermentação , Galactose/análise , Produtos Finais de Glicação Avançada/análise , Carne , Metaboloma , Oligossacarídeos/química , Suínos
3.
Food Chem ; 398: 133915, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988417

RESUMO

In this study, structural characteristics of Fenugreek (FG), Guar (GG), Locust bean (LBG), and Tara gums (TG) and their influence on physicochemical properties of corn starch (CS) gels were investigated. Results showed that FG presented a rigid rod structure, and GG, LBG, and TG showed an extended structure. The Mannose/Galactose (Man/Gal) ratio of FG, GG, LBG, and TG was 1.37, 1.96, 2.99, and 3.46, respectively. The molecular weight (Mw) of FG, GG, LBG, and TG was 0.89 × 106, 2.71 × 106, 3.61 × 106, and 2.77 × 106 Da, respectively. The structure-function relationship indicated that galactomannans with a high Man/Gal ratio and extended structure presented a higher apparent viscosity, formed gel more easily, and could limit retrogradation and improve freeze-thaw stability and textural profile of CS gels. Consequently, the results could be beneficial for the application of galactomannans in starch-based foods to improve their sensory characteristics and storage quality.


Assuntos
Amido , Zea mays , Galactose/análogos & derivados , Géis/química , Humanos , Mananas/química , Amido/química , Relação Estrutura-Atividade , Viscosidade , Zea mays/química
4.
Behav Brain Res ; 436: 114072, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36030906

RESUMO

D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal intake (200 mg/kg and 500 mg/kg, dissolved in tap water) on age-related changes, with emphasis on the prefrontal cortex (PFC) and hippocampus (HIP) of adult male Wistar rats. Memory assessment was followed by histological examination of the PFC and HIP (Nissl staining and Iba-1 immunostaining), while in crude synaptosomal fractions the state of oxidative stress and the expression of proteins involved in glutamatergic signaling was determined. Although applied dosages compromised memory, alterations such as impaired sensory-motor function and aberrant morphology were not detected. In the PFC, analysis of microglia revealed reduction of branching pattern following d-gal intake, in parallel with increased oxidative damage of proteins, lipids and disturbed pro-oxidant antioxidant balance. These changes in the PFC were further accompanied with decreased levels of vesicular glutamate transporter 1, syntaxin-1 and NMDA receptor 2B subunit in both treated groups. Simultaneously, the increased hippocampal oxidative damage of lipids was detected. Results indicate successful provocation of age-related changes following oral d-gal intake, and suggest greater sensitivity of the PFC to d-gal treatment than HIP.


Assuntos
Antioxidantes , Galactose , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Galactose/farmacologia , Hipocampo/metabolismo , Humanos , Lipídeos , Masculino , Estresse Oxidativo , Córtex Pré-Frontal/metabolismo , Proteínas Qa-SNARE/metabolismo , Proteínas Qa-SNARE/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Água/metabolismo , Água/farmacologia
5.
Talanta ; 251: 123760, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964515

RESUMO

The development and application of portable and user-friendly biosensing technology for rapid detection of pathogenic bacteria are essential for human and environmental care. In this work, based on the phenomenon that the filter membrane can selectively separate MnO2 nanosheets (MnO2 NSs) and Mn2+, a novel label-free sensing platform was developed to detect the Escherichia coli (E. coli) using ß-galactosidase (ß-Gal) as a marker. MnO2 NSs were utilized as a dual-mode signal molecule of smartphone-based colorimetric analysis and inductively coupled plasma mass spectrometry (ICP-MS). ß-Gal can catalyze the 4-Aminophenyl ß-D-galactopyranoside (PAPG) to produce p-aminophenol (PAP), which could reduce MnO2 NSs to Mn2+. After selective separation of MnO2 NSs and Mn2+ by the filter, colorimetric detection was achieved with a smartphone by identifying the RGB value of the MnO2 NSs coated membrane, while the Mn2+ in the filtrate was detected by ICP-MS. Under optimal conditions, the limits of detection (LODs) of E. coli by smartphone-based RGB analysis and ICP-MS were 5.6 × 103 CFU mL-1 and 35 CFU mL-1, respectively. This method was successfully used for E. coli assay in meat, vegetables, and fruit samples with the advantages of sensitivity, simplicity, and short incubation time (within 1 h).


Assuntos
Colorimetria , Escherichia coli , Colorimetria/métodos , Galactose , Humanos , Compostos de Manganês , Óxidos , Smartphone , beta-Galactosidase
6.
Methods Mol Biol ; 2589: 361-376, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255637

RESUMO

Experiments determining the chromatin association of histone acetylases (HATs) and deacetylases (HDACs) at the genome-wide level provide precise maps of locus occupancy, but do not allow conclusions on the functional consequences of this locus-specific enrichment. Here we describe a protocol that allows tethering of HATs or HDACs to specific genomic loci upon fusion with a fluorescent protein and a DNA-binding protein such as the E. coli Lac repressor (LacI), which binds to genomically inserted lac operon sequences (lacO) via DNA/protein interactions. Integration of these lacO sequences into a genomic region of interest allows to monitor the functional consequences of HAT/HDAC targeting on chromatin (de)compaction, histone modification, and interaction with other proteins by quantitative light microscopy, as described here. As DNA-binding of LacI can be tightly controlled by the addition of galactose-derivatives, this method also allows to monitor the effects of locus-specific recruitment in a time-resolved manner.


Assuntos
Cromatina , Histona Acetiltransferases , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Cromatina/genética , Repressores Lac/genética , Histonas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Galactose , Histona Desacetilases/metabolismo , DNA/genética , DNA/metabolismo , Acetilação , Acetiltransferases/metabolismo
7.
Food Chem ; 401: 134211, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36122490

RESUMO

Dendrobium officinale is widely consumed owing to its numerous beneficial effects. We aimed to characterize polysaccharides of Dendrobium officinale (DOP) from the stems of Dendrobium officinale Xianhu 2 and clarify whether it benefit the intestinal microbiota and the immune system. The DOP weighed 291 kDa and comprised mannose, glucose, galactose, and rhamnose at 59.31:33.31:1.00:0.51 M ratio. In in vitro/vivo studies, DOP significantly increased benign intestinal microbe proportion (Lactobacillus, etc.), but reduced harmful bacteria (Escherichia_Shigella) (P < 0.05), and significantly increased butyric acid production (P < 0.05). Concentrations of 2 g/L DOP for in vitro fermentation and 100 mg/kg body weight for the mouse model were effective. In mice, DOP significantly reduced CRP, CD3, CD4, and TNF-α levels and increased C4 levels (P < 0.05). DOP might influence the immune system indirectly through regulation of the gut microbiota. Its possible regulation mechanism was that DOP reduced CD4+ Th cells proliferation so that reduced the secretion of TNF-α.


Assuntos
Dendrobium , Microbioma Gastrointestinal , Camundongos , Animais , Manose , Fator de Necrose Tumoral alfa , Galactose , Ramnose , Ácido Butírico , Polissacarídeos , Carboidratos da Dieta , Glucose , Sistema Imunitário
8.
Adv Neurobiol ; 29: 95-116, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255673

RESUMO

Glycoproteins carrying O-linked N-acetylgalactosamine, N-acetylglucosamine, mannose, fucose, glucose, and xylose are found in the nervous system. Lipids are glycosylated by distinct glycosylation enzymes as well. Membrane lipid, ceramide, is modified by the addition of either glucose or galactose to form glycosphingolipid, galactosylceramide, or glucosylceramide. Recent careful analyses by MS have identified glucosylated lipids of cholesterol and phosphatidic acid. These O-linked carbohydrate residues are found primarily on the outer surface of the plasma membrane or in the extracellular space. Their expression is cell or tissue specific and developmentally regulated. Due to their structural diversity, they play important roles in a variety of biological processes such as membrane transport, metabolic stress responses, cell-cell interactions and so on. Discoveries of human diseases associated with glycosylation enzyme deficits have proved modification of lipids and proteins with carbohydrates play critical roles in human health and disease in the nervous systems.


Assuntos
Acetilgalactosamina , Fucose , Humanos , Fucose/metabolismo , Acetilgalactosamina/metabolismo , Acetilglucosamina/metabolismo , Galactose/metabolismo , Manose , Glucosilceramidas , Xilose , Galactosilceramidas , Glicoconjugados/metabolismo , Carboidratos/análise , Glicoproteínas/metabolismo , Sistema Nervoso , Glucose , Ácidos Fosfatídicos
9.
Adv Neurobiol ; 29: 65-93, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255672

RESUMO

Many membrane-resident and secreted proteins, including growth factors and their receptors are N-glycosylated. The initial N-glycan structure is synthesized in the endoplasmic reticulum (ER) as a branched structure on a lipid anchor (dolicholpyrophosphate) and then co-translationally, "en bloc" transferred and linked via N-acetylglucosamine to asparagine within a specific N-glycosylation acceptor sequence of the nascent recipient protein. In the ER and then the Golgi apparatus, the N-linked glycan structure is modified by hydrolytic removal of sugar residues ("trimming") followed by re-glycosylation with additional sugar residues ("processing") such as galactose, fucose or sialic acid to form complex N-glycoproteins. While the sequence of the reactions leading to biosynthesis, "en bloc" transfer and processing of N-glycans is well investigated, it is still not completely understood how N-glycans affect the biological fate and function of N-glycoproteins. This review will discuss the biology of N-glycoprotein synthesis, processing and function with specific reference to the physiology and pathophysiology of the immune and nervous system, as well as infectious diseases such as Covid-19.


Assuntos
Asparagina , COVID-19 , Humanos , Asparagina/química , Asparagina/metabolismo , Fucose , Ácido N-Acetilneuramínico , Galactose , Acetilglucosamina , Glicoproteínas/química , Glicoproteínas/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Lipídeos
10.
Food Chem ; 402: 134289, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36150360

RESUMO

Water-soluble polysaccharides (WSP) were extracted from the pulp of litchi. Its main component was identified as arabinogalactan. The dominant monosaccharide constituents were arabinose and galactose. Galactose and mannose accumulated at the end of storage. ATP, ADP and AMP levels declined with increasing pulp breakdown index. WSP depolymerized which was characterized by a decrease in its content and molecular weight, while its structure remained stable during storage. Polygalacturonase and pectate lyase (PL) were active at the early storage time, and ß-galactosidase (GAL) and α-l-arabinofuranosidase followed thereafter. Except for some pectin methylesterase (LcPME), LcPL, LcGAL and LcPME gene expression was downregulated. It was deduced that depolymerization of polysaccharides was mainly caused by the rupture of the branched side chain and glacturonic acid backbone to smaller repeating units, and both cell wall-degrading enzymes and nonenzymatic factors, such as energy level, participated in the degradation of polysaccharides, and consequently pulp breakdown of litchi.


Assuntos
Litchi , Litchi/química , Poligalacturonase/metabolismo , Arabinose/análise , Água/análise , Galactose/análise , Manose/metabolismo , Polissacarídeos/química , Frutas/química , Monossacarídeos/análise , beta-Galactosidase/metabolismo , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/análise , Trifosfato de Adenosina/metabolismo
11.
PLoS One ; 17(11): e0273868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417410

RESUMO

Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to investigate the therapeutic effects of histone acetyltransferase (HAT) inhibitors. Among the tested HAT inhibitors, TH1834 was the only one that could reverse most of the opacity once it had formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. In lens cross-sections, vacuoles were present in the tissue of the cortical equatorial region of untreated cataract samples. In treated cataract samples, lens tissue regenerated to fill the vacuoles. To identify the genes regulated by HAT inhibitors, qRT-PCR was performed on treated and untreated cataract samples to determine candidate genes. Expression of Acta1 and Stmn4, both of which are involved in the cytoskeleton, were altered significantly in C646+CPTH2 samples. Expression of Emd, a nuclear membrane protein, and Prtfdc1, which is involved in cancer cell proliferation, were altered significantly in CBP30+CPTH2 samples. Acta1, Acta2, Arrdc3, Hebp2, Hist2h2ab, Pmf1, Ppdpf, Rbm3, RGD1561694, Slc16a6, Slfn13, Tagln, Tgfb1i1, and Tuba1c in TH1834 samples were significantly altered. These genes were primarily related to regulation of cell proliferation, the cytoskeleton, and cell differentiation. Expression levels increased with the onset of cataracts and was suppressed in samples treated with HAT inhibitors.


Assuntos
Catarata , Cristalino , Ratos , Animais , Galactose/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Catarata/induzido quimicamente , Catarata/tratamento farmacológico , Catarata/genética , Cristalino/metabolismo , Histonas/metabolismo
12.
J Ovarian Res ; 15(1): 122, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414970

RESUMO

Primary ovarian insufficiency is characterized by accelerated loss of primordial follicles, which results in ovarian failure and concomitant menopause before age 40. About 1-3% of females in the general population are diagnosed with POI; however, greater than 80% of females with the inherited disease Classic Galactosemia will develop POI. Classic Galactosemia is caused by mutations in the GALT gene encoding the enzyme galactose-1 phosphate uridylyltransferase. While dietary restriction of galactose is lifesaving in the neonatal period, the development of complications including primary ovarian insufficiency is not mitigated. Additionally, the pattern(s) of follicle loss have not been completely characterized. The chronic accumulation of aberrant metabolites such as galactose-1-phosphate and galactitol are suspected culprits in the development of the sequelae, yet the mechanisms remain elusive.Our group uses a GalT gene-trapped mouse model to study the pathophysiology of primary ovarian insufficiency in Classic Galactosemia. We recently showed that differences in the Integrated Stress Response pathway occur in mutant ovaries that likely contribute to their primary ovarian insufficiency phenotype. Using immunofluorescent staining of histological sections of ovaries at progressive ages, we saw evidence of altered Integrated Stress Response activity in granulosa cells and primordial oocytes consistent with accelerated primordial follicle growth activation, aberrant DNA damage and/or repair, and increased cellular stress/death. Overall, our findings indicate that abnormal Integrated Stress Response in the Classic Galactosemia model ovary results in accelerated primordial follicle growth activation, sometimes referred to as "burnout." These aberrant early events help further clarify when/how the primary ovarian insufficiency phenotype arises under galactosemic conditions.


Assuntos
Galactosemias , Insuficiência Ovariana Primária , Camundongos , Animais , Feminino , Humanos , Galactosemias/genética , Galactosemias/complicações , Galactosemias/metabolismo , Galactose , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/complicações , UTP-Hexose-1-Fosfato Uridililtransferase/genética , UTP-Hexose-1-Fosfato Uridililtransferase/metabolismo , Modelos Animais de Doenças
13.
Biomolecules ; 12(11)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36358928

RESUMO

ß-Galactosidases (ß-Gal, EC 3.2.1.23) catalyze the cleavage of terminal non-reducing ß-D-galactose residues or transglycosylation reactions yielding galacto-oligosaccharides. In this study, we present the isolation and characterization of a ß-galactosidase from Arion lusitanicus, and based on this, the cloning and expression of a putative ß-galactosidase from Arion vulgaris (A0A0B7AQJ9) in Sf9 cells. The entire gene codes for a protein consisting of 661 amino acids, comprising a putative signal peptide and an active domain. Specificity studies show exo- and endo-cleavage activity for galactose ß1,4-linkages. Both enzymes, the recombinant from A. vulgaris and the native from A. lusitanicus, display similar biochemical parameters. Both ß-galactosidases are most active in acidic environments ranging from pH 3.5 to 4.5, and do not depend on metal ions. The ideal reaction temperature is 50 °C. Long-term storage is possible up to +4 °C for the A. vulgaris enzyme, and up to +20 °C for the A. lusitanicus enzyme. This is the first report of the expression and characterization of a mollusk exoglycosidase.


Assuntos
Galactose , Galactosidases , Animais , beta-Galactosidase/genética , beta-Galactosidase/química , beta-Galactosidase/metabolismo , Galactose/metabolismo , Oligossacarídeos , Moluscos/metabolismo
14.
Front Immunol ; 13: 1021121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353630

RESUMO

Gene duplication (GD) leads to the expansion of gene families that contributes organisms adapting to stress or environment and dealing with the infection of various pathogens. C-type lectins (CTLs) in crustaceans undergo gene expansion and participate in various immune responses. However, the functions of different CTL produced by GD are not fully characterized. In the present study, two CTL genes (designated as PcLec-EPS and PcLec-QPS, respectively) were identified from Procambarus clarkii. PcLec-EPS and PcLec-QPS originate from GD and the main difference between them is exon 3. PcLec-EPS and PcLec-QPS respectively contains EPS and QPS motif in their carbohydrate recognition domain. The mRNA levels of PcLec-EPS and PcLec-QPS in hemocytes, gills, intestine and lymph underwent time-dependent enhancement after D-Mannose and D-Galactose challenge. Recombinant PcLec-EPS and PcLec-QPS could bind to carbohydrates and microbes, and agglutinate bacteria. The results of experiments on recombinant protein injection and RNA interference indicate that PcLec-EPS and PcLec-QPS can respectively strong recognize and bind D-Mannose and D-Galactose, activate the Relish transcriptional factor, and further upregulate the expression of different antimicrobial peptides (AMPs). In addition, these two CTLs and Relish could positively regulate the expression of each other, suggesting that there is a positive feedback loop between two CTLs and Relish that regulates the expression of AMPs. It may contribute to the expansion of the immune response for host quickly and efficiently eliminating pathogenic microorganisms. This study provides new knowledge for clear understanding the significance and function of different CTL generated by GD in immune defenses in crustacean.


Assuntos
Astacoidea , Lectinas Tipo C , Animais , Lectinas Tipo C/metabolismo , Peptídeos Antimicrobianos , Duplicação Gênica , Manose , Galactose , Retroalimentação
15.
J Chromatogr A ; 1685: 463589, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36351322

RESUMO

Immunoglobulin A nephropathy (IgAN) is a highly prevalent autoimmune renal disease. Human IgA1 with galactose deficiency in the hinge region (HR) has been identified as an autoantigen for this disease. Therefore, analyzing IgA1 HR glycoforms in biofluids is important for biomarker discovery. Herein, an analytical method that includes one-pot sample preparation with unbiased plasma IgA purification, dual internal standard addition, and sensitive ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectroscopy (UHPLC-QqQ-MS/MS) was developed. Targeted O-glycopeptides detection was performed in pooled plasma with the validation of theoretical retention times, enzymatic treatment outcomes, product ion scans, and signal repeatability. A total of 42 IgA1 O-glycopeptides with N-acetylgalactosamines, galactoses, and sialic acids were determined from 8 µL of plasma. The newly developed method was applied to plasma samples from 16 non-IgAN controls and 19 IgAN patients. Comparing the 42 targets, 16 IgA1 HR O-glycopeptides were statistically different between the two groups (p<0.05). Decreased sialylation was identified in the IgA1 hinge region of IgAN patients, which was also correlated with the estimated glomerular filtration rate (eGFR). The developed method is sensitive and precise and can be used to identify plasma biomarkers for IgA nephropathy.


Assuntos
Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/diagnóstico , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Imunoglobulina A , Glicopeptídeos/química , Galactose
16.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364921

RESUMO

Placental extract has been used for skin care and delaying skin aging. Cow placenta is an abundant resource with a large mass, which has not been harnessed effectively. Cow placenta extract (CPE) has the functions of antioxidation, anti-inflammatory, promoting growth and development, and promoting hair growth. However, little is known about the effect of oral administration of cow placenta extract on skin conditions. Therefore, the present study aimed to investigate the antioxidant capacity of CPE in vitro and in vivo and its protective effect on d-galactose (D-gal) induced skin aging in mice. The results showed that CPE had strong free radical scavenging, reducing and metal chelating activities. CPE can increase the activity of catalase (CAT), glutathione peroxidase (GSH-Px), peroxidase (POD), superoxide dismutase (SOD), and the content of glutathione (GSH), decrease the content of malondialdehyde (MDA). Moreover, CPE can decrease the gene and protein expression of matrix metalloproteinase 1a (MMP-1a) and matrix metalloproteinase 3 (MMP-3) and increase the expression of transforming growth factor-ß (TGF-ß) and tissue inhibitor of metalloproteinase 1 (TIMP-1) of mouse skin. Histopathological analysis showed CPE reduced the collagen damage caused by D-gal, increased collagen synthesis and reduced its degradation to delay skin aging.


Assuntos
Antioxidantes , Envelhecimento da Pele , Animais , Bovinos , Feminino , Camundongos , Gravidez , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galactose/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Extratos Vegetais/farmacologia , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo
17.
J Transl Med ; 20(1): 496, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316782

RESUMO

BACKGROUND: Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC). METHODS: Sialic acid (Sia) and Gal/GalNAc residues on OC A2780, OVCAR3, and ID8 cells treated with α2-3 neuraminidase (α2-3NA) and α2-6NA, and Sigec-9 or Siglec-E and MGL on DCs pulsed with desialylated OC cells were identified using flow cytometry (FCM); RT-qPCR determined IFNG expression of T cells, TRBV was sequenced using Sanger sequencing and cytotoxicity of αß T cells was measured with LDH assay; Anti-tumor immunity in vivo was validated via vaccination with desialylated whole-cell ID8 vaccine (ID8 DWCTVs). RESULTS: Gal/GalNAc but not Sia residues were significantly increased in the desialylated OC cells. α2-3NA-modified DWCTV increased MGL but decreased Siglec-9 or Siglec E expression on DCs. MGLbright/Siglec-9dim DCs significantly up-regulated IFNG expression and CD4/CD8 ratio of T cells and diversified the TCR repertoire of αß T-cells that showed enhanced cytotoxic activity. Vaccination with α2-3NA-modified ID8 DWCTVs increased MGLbright/Siglec-Edim DCs in draining lymph nodes, limited tumor growth, and extended survival in tumor-challenged mice. CONCLUSION: Desialylated tumor cell vaccine could promote anti-tumor immunity and provide a strategy for OC immunotherapy in a clinical setting.


Assuntos
Vacinas Anticâncer , Neoplasias Ovarianas , Humanos , Camundongos , Animais , Feminino , Epitopos , Ácido N-Acetilneuramínico/metabolismo , Linhagem Celular Tumoral , Apoptose , Neoplasias Ovarianas/terapia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Antígenos , Galactose/metabolismo
18.
Sci Rep ; 12(1): 17116, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224240

RESUMO

The valorization of new polymer sources from underutilized plants as structuring, encapsulating, and texturizing agents for food and nutraceutical applications is gaining attention. This provides an opportunity where inexpensive plant-sourced biopolymers can play an impactful role, on both ecological and economic aspects performing equivalently effectual yet cost-effective substitutes to synthetic polymers. With this aim, we explored the use of mucilage from Althea rosea and reveal its physicochemical, in vitro antidiabetic and antihypertensive activity. Besides, structural, micrometric, crystallization, and anti-microbial properties was also seen. We determined the probable structure of the extracted mucilage by FTIR which confirmed the residues of saccharides as galactose and uronic acid with α and ß configurations. It consists of 78.26% carbohydrates, 3.51% ashes, and 3.72% proteins. Here, we show that the mucilage offered protection to DNA against the oxidative damage caused by (-OH) radicals and the morphology of the mucilage particles displayed a fibrillary material settled in a net-like, tangled structure. Our results demonstrate that the reconstituted mucilage powder exhibited good water holding capacity (2.89 g water/g mucilage), solubility (27.33%), and oil holding capacity (1.79 g oil/g mucilage). Moreover, high emulsifying property (95.83%) and foaming capacity (17.04%) was noted. Our results indicate that A.rosea mucilage can potentially serve as economical and eco-friendly hydrocolloid substitute for the food and nutraceutical industry owing to its functional, hypo-lipidemic, anti-hyperglycemic, antioxidant, and anti-bacterial properties.


Assuntos
Mucilagem Vegetal , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Coloides/química , Galactose , Hipoglicemiantes/farmacologia , Mucilagem Vegetal/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Pós , Ácidos Urônicos , Água/química
19.
Sci Rep ; 12(1): 17084, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224264

RESUMO

Slowing down age-related neurocognitive impairment has been a challenge. We evaluated the therapeutic effects of metformin in D-galactose-induced aging. Additionally, we studied the potential molecular mechanisms that could be responsible for metformin's anti-aging effects. Thirty male rats were equally divided into: 1-control group, which received saline solution, 2-D-galactose (D-gal) group, which received D-galactose (100 mg/kg/day) by gastric lavage for eight weeks, and 3-D-galactose + Metformin (D-gal + Met) treated group, which received D-galactose + metformin (200 mg/kg/day) by gastric lavage for eight weeks. Neurocognitive assessment was done. Measurement of inflammatory, oxidative stress, and BDNF biomarkers was performed. AMPK and PI3K genes expression were assessed. Hippocampal tissues were dissected for histopathological and immunohistochemical studies. D-gal resulted in neurocognitive impairments, elevation of inflammatory biomarkers, altered oxidative stress markers, decreased BDNF, decreased expression of synaptophysin and Bcl2 with increased expression of Caspase-3, and down-regulation of AMPK and PI3K genes. Neurodegenerative changes were present in the hippocampus. Metformin restored significantly D-gal induced neurodegenerative changes. We concluded that metformin could alleviate age-induced neurocognitive deficit via amelioration of neuroinflammation, attenuation of oxidative stress, reduction of apoptosis, as well as promotion of synaptic plasticity. These mechanisms could be mediated via the activation of the AMPK/BDNF/PI3K pathway.


Assuntos
Galactose , Metformina , Proteínas Quinases Ativadas por AMP/metabolismo , Envelhecimento/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/metabolismo , Galactose/farmacologia , Masculino , Metformina/farmacologia , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Solução Salina/farmacologia , Sinaptofisina/metabolismo
20.
Oxid Med Cell Longev ; 2022: 8488269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199421

RESUMO

Population aging has led to increased sick sinus syndrome (SSS) incidence; however, no effective and safe medical therapy has been reported thus far. Yixin-Fumai granules (YXFMs), a Chinese medicine granule designed for bradyarrhythmia treatment, can effectively increase SSS patients' heart rate. Senescence-induced sinoatrial node (SAN) degeneration is an important part of SSS pathogenesis, and older people often show high levels of oxidative stress; reactive oxygen species (ROS) accumulation in the SAN causes abnormal SAN pacing or conduction functions. The current study observed the protective effects of YXFMs on senescent SAN and explored the relationship between the NRF-2/HO-1 pathway, SHOX2, and T-type calcium channels. We selected naturally senescent C57BL/6 mice with bradycardia to simulate SSS; electrocardiography, Masson's trichrome staining, and DHE staining were used to assess SAN function and tissue damage. Immunofluorescence staining and Western blotting were used to assay related proteins. In vitro, we treated human-induced pluripotent stem cell-derived atrial myocytes (hiPSC-AMs) and mouse atrial myocyte-derived cell line HL-1 with D-galactose to simulate senescent SAN-pacemaker cells. CardioExcyte96 was used to evaluate the pulsatile function of the hiPSC-AMs, and the mechanism was verified by DCFH-DA, immunofluorescence staining, RT-qPCR, and Western blotting. The results demonstrated that YXFMs effectively inhibited senescence-induced SAN hypofunction, and this effect possibly originated from scavenging of ROS and promotion of NRF-2, SHOX2, and T-type calcium channel expression. In vitro experiment results indicated that ML385, si-SHOX2, LDN193189, and Mibefradil reversed YXFMs' effects. Moreover, we, for the first time, found that ROS accumulation may hinder SHOX2 expression; YXFMs can activate SHOX2 through the NRF-2/HO-1 pathway-mediated ROS scavenging and then regulate CACNA1G through the SHOX2/BMP4/GATA4/NKX2-5 axis, improve T-type calcium channel function, and ameliorate the SAN dysfunction. Finally, through network pharmacology and molecular docking, we screened for the most stable YXFMs compound that docks to NRF-2, laying the foundation for future studies.


Assuntos
Canais de Cálcio Tipo T , Heme Oxigenase-1/metabolismo , Proteínas de Homeodomínio , Fator 2 Relacionado a NF-E2/metabolismo , Aceleração , Idoso , Animais , Galactose , Frequência Cardíaca , Proteínas de Homeodomínio/metabolismo , Humanos , Medicina Tradicional Chinesa , Mibefradil , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo
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