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1.
Food Chem ; 462: 140951, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39213975

RESUMO

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.


Assuntos
Anti-Inflamatórios , Doenças Inflamatórias Intestinais , Polifenóis , Polissacarídeos , Polifenóis/química , Polifenóis/farmacologia , Polifenóis/administração & dosagem , Humanos , Polissacarídeos/química , Polissacarídeos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia
2.
Food Chem ; 462: 141010, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39217745

RESUMO

In this study, we investigated how different proportions blends of Rhamnogalacturonan-I pectic polysaccharides and hesperidin impact the gut microbiota and metabolites using an in vitro simulated digestion and fermentation model. The results indicated that both of them could modulate the gut microbiota and produce beneficial metabolites. However, their blends in particular proportions (such as 1:1) exhibited remarkable synergistic effects on modulating the intestinal microenvironment, surpassing the effects observed with individual components. Specifically, these blends could benefit the host by increasing short-chain fatty acids production (such as acetate), improving hesperidin bioavailability, producing more metabolites (such as hesperetin, phenolic acids), and promoting the growth of beneficial bacteria. This synergistic and additive effect was inseparable from the role of gut microbiota. Certain beneficial bacteria, such as Blautia, Faecalibacterium, and Prevotella, exhibited strong preferences for those blends, thereby contributing to host health through participating in carbohydrate and flavonoid metabolism.


Assuntos
Bactérias , Microbioma Gastrointestinal , Hesperidina , Pectinas , Hesperidina/farmacologia , Hesperidina/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/isolamento & purificação , Humanos , Pectinas/metabolismo , Pectinas/química , Pectinas/farmacologia , Fermentação , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Polissacarídeos/química , Ácidos Graxos Voláteis/metabolismo , Digestão , Modelos Biológicos
3.
Food Chem ; 462: 141024, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39217751

RESUMO

With the aim of expanding the potential application scope of mulberries, eleven pH-switchable deep eutectic solvents were screened for the ultrasonic-assisted extraction of mulberry polysaccharides, and a salt/salt aqueous two-phase system was constructed for the efficient separation of mulberry polysaccharides by regulating the system pH. DES-9 (tetraethylammonium chloride: octanoic acid molar ratio = 1: 2) with a critical response pH value of approximately 6.1 was concluded to be the best extraction solvent for extracting mulberry polysaccharides. A maximum polysaccharide extraction yield of 270.71 mg/g was obtained under the optimal conditions. The maximum polysaccharide extraction efficiency was 78.09 % for the pH-driven tetraethylammonium chloride/K2HPO4 aqueous two-phase system. An acidic ß-pyran mulberry polysaccharide with a low-molecular weight of 9.26 kDa and a confirmed monosaccharide composition were obtained. This efficient and environmentally friendly polysaccharide separation method offers a new approach for the efficient extraction and utilization of other plant polysaccharides.


Assuntos
Solventes Eutéticos Profundos , Morus , Extratos Vegetais , Polissacarídeos , Morus/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Concentração de Íons de Hidrogênio , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Solventes Eutéticos Profundos/química , Fracionamento Químico/métodos , Peso Molecular , Frutas/química , Cloreto de Sódio/química
4.
J Chromatogr A ; 1735: 465318, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39244913

RESUMO

Protein glycosylation, one of the most important biologically relevant post-translational modifications for biomarker discovery, faces analytical challenges due to heterogeneous glycosite, diverse glycans, and mass spectrometry limitations. Glycopeptide enrichment by removing abundant hydrophobic peptides helps overcome some of these obstacles. Hydrophilic interaction liquid chromatography (HILIC), known for its selectivity, glycan separations, intact glycopeptide enrichment, and compatibility with mass spectrometry, has seen recent advancements in stationary phases like Amide-80, glycoHILIC, amino acids or peptides for improved HILIC-based glycopeptide analysis. Utilization of these materials can improve glycopeptide enrichment through solid-phase extraction and separation via high-performance liquid chromatography. Additionally, using glycopeptides themselves to modify HILIC stationary phases holds promise for improving selectivity and sensitivity in glycosylation analysis. Additionally, HILIC has capability to assess the information about glycosites and structural information of glycans. This review summarizes recent breakthroughs in HILIC stationary materials, highlighting their impact on glycopeptide analysis. Ongoing research on advanced materials continues to refine HILIC's performance, solidifying its value as a tool for exploring protein glycosylation.


Assuntos
Glicopeptídeos , Interações Hidrofóbicas e Hidrofílicas , Polissacarídeos , Glicopeptídeos/química , Glicopeptídeos/isolamento & purificação , Glicopeptídeos/análise , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/análise , Glicosilação , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Extração em Fase Sólida/métodos , Humanos
5.
Nat Commun ; 15(1): 7925, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271664

RESUMO

Glycan-mediated interactions play a crucial role in biology and medicine, influencing signalling, immune responses, and disease pathogenesis. However, the use of glycans in biosensing and diagnostics is limited by cross-reactivity, as certain glycan motifs can be recognised by multiple biologically distinct protein receptors. To address this specificity challenge, we report the enzymatic synthesis of a 150-member library of site-specifically fluorinated Lewisx analogues ('glycofluoroforms') using naturally occurring enzymes and fluorinated monosaccharides. Subsequent incorporation of a subset of these glycans into nanoparticles or a microarray revealed a striking spectrum of distinct binding intensities across different proteins that recognise Lewisx. Notably, we show that for two proteins with unique binding sites for Lewisx, glycofluoroforms exhibited enhanced binding to one protein, whilst reduced binding to the other, with selectivity governed by fluorination patterns. We finally showcase the potential diagnostic utility of this approach in glycofluoroform-mediated bacterial toxin detection by lateral flow.


Assuntos
Polissacarídeos , Polissacarídeos/metabolismo , Polissacarídeos/química , Ligação Proteica , Sítios de Ligação , Humanos , Halogenação , Antígenos CD15/metabolismo , Antígenos CD15/química , Nanopartículas/química
6.
Nutrients ; 16(17)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39275156

RESUMO

The gut microbiota constitutes a complex ecosystem, comprising trillions of microbes that have co-evolved with their host over hundreds of millions of years. Over the past decade, a growing body of knowledge has underscored the intricate connections among diet, gut microbiota, and human health. Bioactive polysaccharides (BPs) from natural sources like medicinal plants, seaweeds, and fungi have diverse biological functions including antioxidant, immunoregulatory, and metabolic activities. Their effects are closely tied to the gut microbiota, which metabolizes BPs into health-influencing compounds. Understanding how BPs and gut microbiota interact is critical for harnessing their potential health benefits. This review provides an overview of the human gut microbiota, focusing on its role in metabolic diseases like obesity, type II diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular diseases. It explores the basic characteristics of several BPs and their impact on gut microbiota. Given their significance for human health, we summarize the biological functions of these BPs, particularly in terms of immunoregulatory activities, blood sugar, and hypolipidemic effect, thus providing a valuable reference for understanding the potential benefits of natural BPs in treating metabolic diseases. These properties make BPs promising agents for preventing and treating metabolic diseases. The comprehensive understanding of the mechanisms by which BPs exert their effects through gut microbiota opens new avenues for developing targeted therapies to improve metabolic health.


Assuntos
Microbioma Gastrointestinal , Doenças Metabólicas , Polissacarídeos , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Polissacarídeos/farmacologia , Doenças Metabólicas/microbiologia , Doenças Metabólicas/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Animais , Obesidade/microbiologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo
7.
Nutrients ; 16(17)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39275167

RESUMO

Despite recent advances, pharmacological treatments of diabetic retinopathy (DR) do not directly address the underlying oxidative stress. This study evaluates the efficacy of a nutraceutical formulation based on maltodextrinated grape pomace extract (MaGPE), an oxidative stress inhibitor, in managing DR. A 6-month, randomized, placebo-controlled clinical trial involving 99 patients with mild to moderate non-proliferative DR was conducted. The MaGPE group showed improvement in best-corrected visual acuity (BCVA) values at T3 (p < 0.001) and T6 (p < 0.01), a reduction in CRT (at T3 and T6, both p < 0.0001) and a stabilization of vascular perfusion percentage, with slight increases at T3 and T6 (+3.0% and +2.7% at T3 and T6, respectively, compared to baseline). Additionally, the levels of reactive oxygen metabolite derivatives (dROMs) decreased from 1100.6 ± 430.1 UCARR at T0 to 974.8 ± 390.2 UCARR at T3 and further to 930.6 ± 310.3 UCARR at T6 (p < 0.05 vs. T0). Similarly, oxidized low-density lipoprotein (oxLDL) levels decreased from 953.9 ± 212.4 µEq/L at T0 to 867.0 ± 209.5 µEq/L at T3 and markedly to 735.0 ± 213.7 µEq/L at T6 (p < 0.0001 vs. T0). These findings suggest that MaGPE supplementation effectively reduces retinal swelling and oxidative stress, contributing to improved visual outcomes in DR patients.


Assuntos
Retinopatia Diabética , Suplementos Nutricionais , Estresse Oxidativo , Extratos Vegetais , Polissacarídeos , Acuidade Visual , Vitis , Humanos , Retinopatia Diabética/tratamento farmacológico , Vitis/química , Masculino , Feminino , Extratos Vegetais/farmacologia , Pessoa de Meia-Idade , Acuidade Visual/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Idoso , Resultado do Tratamento , Lipoproteínas LDL/sangue , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo
8.
Nat Commun ; 15(1): 8055, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277585

RESUMO

Precision mapping of site-specific glycans using mass spectrometry is vital in glycoproteomics. However, the diversity of glycan compositions across species often exceeds database capacity, hindering the identification of rare glycans. Here, we introduce pGlycoNovo, a software within the pGlyco3 software environment, which employs a glycan first-based full-range Y-ion dynamic searching strategy. pGlycoNovo enables de novo identification of intact glycopeptides with rare glycans by considering all possible monosaccharide combinations, expanding the glycan search space to 16~1000 times compared to non-open search methods, while maintaining accuracy, sensitivity and speed. Reanalysis of SARS Covid-2 spike protein glycosylation data revealed 230 additional site-specific N-glycans and 30 previously unreported O-glycans. pGlycoNovo demonstrated high complementarity to six other tools and superior search speed. It enables characterization of site-specific N-glycosylation across five evolutionarily distant species, contributing to a dataset of 32,549 site-specific glycans on 4602 proteins, including 2409 site-specific rare glycans, and uncovering unexpected glycan fragments.


Assuntos
Glicopeptídeos , Polissacarídeos , Software , Glicoproteína da Espícula de Coronavírus , Glicosilação , Polissacarídeos/metabolismo , Polissacarídeos/química , Humanos , Glicopeptídeos/química , Glicopeptídeos/metabolismo , Glicopeptídeos/análise , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , SARS-CoV-2/metabolismo , SARS-CoV-2/química , Animais , Proteômica/métodos , COVID-19/virologia
9.
Sci Rep ; 14(1): 21504, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277703

RESUMO

WSGP has demonstrated significant potential for various bioactive effects. However, limited research has explored their anti-ulcerative colitis (UC) effects and mechanism on the colonic system and gut microbial metabolites. We evaluated the ameliorative effects of WSGP on the UC mice model. Using H&E to assess histological injury of colon morphology, AB-PAS staining to detect mucin secretion from goblet cells and the mucous layer, IF to evaluate the expression of intercellular tight junction proteins, ELISA to measure inflammatory factors, WB analysis to measure protein expression of inflammatory signaling pathways, RT-qPCR to quantify gene transcription of inflammatory factors, and LC-MS to analyze metabolites in mouse cecum contents. WSGP supplementation increased food intake, body weight, and colon length while reducing disease activity and histological scores in colitis-afflicted mice. WSGP mitigated colonic tissue damage and restored intestinal barrier integrity by suppressing NF-κB/STAT3 signaling, thereby decreasing gene transcription, protein expression of proinflammatory factors, and nitric oxide production. Additionally, WSGP improved UC by altering the variety of intestinal microbial metabolites. This study demonstrates that WSGP supplementation attenuates UC mice by suppressing the NF-κB/STAT3 signaling pathway, enhancing mucosal barrier function, reducing pro-inflammatory cytokines, and modulating gut microbial metabolites.


Assuntos
Colite Ulcerativa , Alho , Microbioma Gastrointestinal , Mucosa Intestinal , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Polissacarídeos/farmacologia , Alho/química , Colite Ulcerativa/microbiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Masculino , Colo/metabolismo , Colo/patologia , Colo/efeitos dos fármacos , Colo/microbiologia , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Água , Camundongos Endogâmicos C57BL
10.
Int J Mol Sci ; 25(17)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39273189

RESUMO

Glycan profile comparisons are one of the most tedious analytical exercises for establishing compliance with recombinant therapeutic protein batches. Based on its intensive research, the FDA has confirmed that lectin array binding with fluorescent monitoring is the fastest and most reliable method for profile comparisons. Using a database of over 150 biological products expressed in nine diverse mammalian cell systems, the FDA immobilized 74 lectins to study their binding using fluorescently labeled glycoproteins. The FDA identified nine distinct lectins from a custom-designed lectin microarray: rPhoSL, rOTH3, RCA120, rMan2, MAL_I, rPSL1a, PHAE, rMOA, and PHALs, which detect core fucose, terminal GlcNAc, terminal ß-galactose, high mannose, α-2,3-linked sialic acids, α-2,6-linked sialic acids, bisecting GlcNAc, terminal α-galactose, and triantennary structures, respectively. This method can be used for screening and routine testing and to monitor batch-to-batch variability of therapeutic proteins, including establishing analytical similarity as a crucial part of biosimilar development.


Assuntos
Medicamentos Biossimilares , Lectinas , Polissacarídeos , Lectinas/metabolismo , Lectinas/química , Polissacarídeos/química , Polissacarídeos/análise , Medicamentos Biossimilares/análise , Medicamentos Biossimilares/química , Humanos , Estados Unidos , United States Food and Drug Administration , Glicoproteínas/química , Glicoproteínas/análise , Aprovação de Drogas , Fluorescência , Animais
11.
Int J Mol Sci ; 25(17)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39273352

RESUMO

Highly purified human menopausal gonadotropin (HP-hMG [Menopur®, Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur® and two of Menogon® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid®) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.


Assuntos
Gonadotropina Coriônica , Hormônio Luteinizante , Espectrometria de Massas em Tandem , Humanos , Gonadotropina Coriônica/urina , Gonadotropina Coriônica/análise , Hormônio Luteinizante/urina , Hormônio Luteinizante/análise , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Polissacarídeos/análise , Polissacarídeos/química , Polissacarídeos/urina , Glicosilação , Feminino , Menotropinas/urina , Menotropinas/análise , Hormônio Foliculoestimulante/urina , Hormônio Foliculoestimulante/análise , Oxirredução , Glicopeptídeos/análise , Glicopeptídeos/química , Glicopeptídeos/urina
12.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39273687

RESUMO

The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.


Assuntos
Adipogenia , Metabolismo Energético , Fucose , Alimento Funcional , Obesidade , Polissacarídeos , Alga Marinha , Peixe-Zebra , Animais , Metabolismo Energético/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Polissacarídeos/química , Polissacarídeos/farmacologia , Alga Marinha/química , Fucose/metabolismo , Adipogenia/efeitos dos fármacos , Camundongos , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos , Humanos , Sulfatos/química , Sulfatos/metabolismo , PPAR gama/metabolismo , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/uso terapêutico , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo
13.
MAbs ; 16(1): 2400414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39245969

RESUMO

During the development process of therapeutic monoclonal antibodies (mAbs), it is crucial to control (critical) quality attributes such as N-glycosylation influencing pharmacokinetics (PK) and Fc effector functions. Previous reports have shown that mAbs containing high-mannose N-glycans are cleared faster from blood circulation, leading to reduced half-lives. The high-mannose N-glycan content of mAbs can be influenced during the cell culture process by factors such as cell lines, process conditions, and media. Furthermore, mAbs have either one high mannose N-glycan (asymmetrical high-mannose glyco-pair) or two high mannose N-glycans (symmetrical high-mannose glyco-pair). The hypothesis that the mannose receptor (MR, CD206) accelerates clearance by facilitating their internalization and subsequent lysosomal degradation is widespread. However, the interaction between MR and mAbs has not been explicitly demonstrated. This study aimed to investigate this interaction, providing the first systematic demonstration of MR binding to the Fc region of mAbs with high-mannose N-glycans. Two novel analytical methods, MR surface plasmon resonance and MR affinity chromatography, were developed and applied to investigate the MR-mAb interaction. The interaction is found to be dependent on high-mannose content, but is independent of the mAb format or sequence. However, different glyco-pairs exhibited varying binding affinities to the MR, with the symmetrical high-mannose glyco-pair showing the strongest binding properties. These findings strengthen the hypothesis for the MR-mediated mAb interaction and contribute to a deeper understanding of the MR-mAb interaction, which could affect the criticality of high-mannose containing mAbs development strategies of IgG-based molecules and improve their PK profiles.


Assuntos
Anticorpos Monoclonais , Lectinas Tipo C , Receptor de Manose , Lectinas de Ligação a Manose , Manose , Polissacarídeos , Receptores de Superfície Celular , Polissacarídeos/metabolismo , Polissacarídeos/química , Lectinas de Ligação a Manose/metabolismo , Receptores de Superfície Celular/metabolismo , Lectinas Tipo C/metabolismo , Manose/metabolismo , Manose/química , Humanos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/imunologia , Animais , Glicosilação , Cricetulus , Células CHO , Ressonância de Plasmônio de Superfície , Ligação Proteica
14.
Microbiome ; 12(1): 170, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39252128

RESUMO

BACKGROUND: Clean energy hydrogen (H2) produced from abundant lignocellulose is an alternative to fossil energy. As an essential influencing factor, there is a lack of comparison between constant temperatures (35, 55 and 65 °C) and gradient heating temperature (35 to 65 °C) on the H2 production regulation potential from lignocellulose-rich straw via high-solid anaerobic digestion (HS-AD). More importantly, the microbial mechanism of temperature regulating H2 accumulation needs to be investigated. RESULTS: Constant 65 °C led to the lowest lignin residue (1.93%) and the maximum release of cellulose and hemicellulose, and the highest H2 production (26.01 mL/g VS). H2 production at 35 and 55 °C was only 14.56 and 24.13 mL/g VS, respectively. In order to further explore the potential of ultra-high temperature (65 °C), HS-AD was performed by gradient heating conditions (35 to 65 °C). However, compared to constant 65 °C, gradient heating conditions led to higher lignin residue (2.49%) and lower H2 production (13.53 mL/g VS) than gradient heating conditions (47.98%). In addition, metagenomic analysis showed the cellulose/hemicellulose hydrolyzing bacteria and genes (mainly Thermoclostridium, and xynA, xynB, abfA, bglB and xynD), H2-producing bacteria and related genes (mainly Thermoclostridium, and nifD, nifH and nifK), and microbial movement and metabolic functions were enriched at 65 °C. However, the enrichment of two-component systems under gradient heating conditions resulted in a lack of highly-enriched ultra-high-temperature cellulose/hemicellulose hydrolyzing genera and related genes but rather enriched H2 consumption genera and genes (mainly Acetivibrio, and hyaB and hyaA) resulting in a weaker H2 production. CONCLUSIONS: The lignin degradation process does not directly determine H2 accumulation, which was actually regulated by bacteria/genes contributing to H2 production/consumption. In addition, it is temperature that enhances the hydrolysis process of lignin rather than lignin-degrading enzymes, bacteria and genes by promoting microbial material transfer and metabolism. In terms of temperature, one of the key parameters of HS-AD for H2 production, we developed an important regulatory strategy, enriched the theoretical basis of temperature regulation for H2 production to further expanded the research horizon in this field. Video Abstract.


Assuntos
Hidrogênio , Lignina , Hidrogênio/metabolismo , Lignina/metabolismo , Anaerobiose , Temperatura Alta , Celulose/metabolismo , Polissacarídeos/metabolismo , Metagenômica/métodos , Temperatura , Bactérias/metabolismo , Bactérias/classificação , Bactérias/genética
15.
Proc Natl Acad Sci U S A ; 121(38): e2412534121, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39259590

RESUMO

Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.


Assuntos
Cálcio , Parede Celular , Cryptococcus neoformans , Melaninas , Cryptococcus neoformans/metabolismo , Cryptococcus neoformans/crescimento & desenvolvimento , Melaninas/metabolismo , Cálcio/metabolismo , Parede Celular/metabolismo , Cápsulas Fúngicas/metabolismo , Humanos , Polissacarídeos/metabolismo , Polissacarídeos Fúngicos/metabolismo
16.
J Am Coll Cardiol ; 84(12): 1092-1103, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39260931

RESUMO

BACKGROUND: B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide is the only blood biomarker in established risk calculators for pulmonary arterial hypertension (PAH). Profiling systemic-originated plasma immunoglobulin G (IgG) N-glycans, which reflect different components of the pathophysiology of PAH including immune dysregulation and inflammation, may improve PAH risk assessment. OBJECTIVES: This study sought to identify plasma IgG N-glycan biomarkers that predict survival in PAH to improve risk assessment. METHODS: This cohort study examined 622 PAH patients from 2 national centers (Beijing [discovery] cohort: n = 273; Shanghai [validation] cohort: n = 349). Plasma IgG N-glycomes were profiled by a robust mass spectrometry-based method. Prognostic IgG N-glycan traits were identified and validated in the 2 cohorts using Cox regression and Kaplan-Meier survival analyses. The added value of IgG N-glycan traits to previously established risk models was assessed using Harrell C-indexes and survival analysis. RESULTS: Plasma IgG fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377; 95% CI: 0.168-0.845; P = 0.018) with confirmation in the validation cohort (HR: 0.445; 95% CI: 0.264-0.751; P = 0.005). IgG fucosylation remained a robust predictor of mortality in combined cohorts after full adjustment and in subgroup analyses. Integrating IgG fucosylation into previously established risk models improved their predictive capacity, marked by an overall elevation in Harrell C-indexes. IgG fucosylation was useful in further stratifying the intermediate-risk patients classified by a previously established model. CONCLUSIONS: Plasma IgG fucosylation informs PAH prognosis independent of established factors, offering additional value for predicting PAH outcomes.


Assuntos
Biomarcadores , Imunoglobulina G , Humanos , Feminino , Masculino , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Prognóstico , Biomarcadores/sangue , Adulto , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/mortalidade , Estudos de Coortes , Polissacarídeos/sangue , Idoso , Medição de Risco/métodos , China/epidemiologia
17.
Theranostics ; 14(12): 4622-4642, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239516

RESUMO

Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. coli) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.


Assuntos
Disfunção Cognitiva , Dieta Hiperlipídica , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Polissacarídeos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Disfunção Cognitiva/terapia , Polissacarídeos/farmacologia , Masculino , Disbiose/terapia , Colo/microbiologia , Escherichia coli , Butiratos/metabolismo , Proteobactérias/isolamento & purificação , Proteobactérias/efeitos dos fármacos , Modelos Animais de Doenças
18.
Molecules ; 29(17)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39274983

RESUMO

This study investigated the structural composition and antioxidant properties of pectic polysaccharides extracted from Rohdea japonica (Thunb.) Roth. Pectins, which belong to a complex category of acidic polysaccharides, possess a wide range of biological effects stemming from their distinctive structural domains. The polysaccharides were extracted using water, and were subsequently purified through ion exchange and gel permeation chromatography. In order to elucidate their structural features, Fourier Transform Infrared Spectroscopy and Nuclear Magnetic Resonance techniques were applied. Two specific polysaccharides, WRJP-A2a and WRJP-A3b, with molecular weights of 42.7 kDa and 64.1 kDa, respectively, were identified to contain varying proportions of homogalacturonan, rhamnogalacturonan I, and rhamnogalacturonan II domains. Regarding antioxidant capacity, WRJP-A3b exhibited superior scavenging capabilities against DPPH, ABTS, and hydroxyl radicals, potentially attributed to its higher galacturonic acid content and abundance of homogalacturonan domains. These results enhance our comprehension of the structure-activity interplay of pectic polysaccharides sourced from Rohdea japonica (Thunb.) Roth and their potential utility in the healthcare and functional food sectors.


Assuntos
Antioxidantes , Pectinas , Polissacarídeos , Pectinas/química , Pectinas/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Peso Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Espectroscopia de Ressonância Magnética , Picratos/química , Picratos/antagonistas & inibidores , Ácidos Hexurônicos
19.
Adv Food Nutr Res ; 112: 301-345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39218505

RESUMO

Hydrogel delivery systems based on polysaccharides and proteins have the ability to protect functional substances from chemical degradation, control/target release, and increase bioavailability. This chapter summarizes the recent progress in the utilization of hydrogel delivery systems for nutritional interventions. Various hydrogel delivery systems as well as their preparation, structure, and properties are given. The applications for the encapsulation, protection, and controlled delivery of functional substances are described. We also discuss their potential and challenges in managing chronic diseases such as inflammatory bowel disease, obesity, liver disease, and cancer, aiming at providing theoretical references for exploring novel hydrogel delivery systems and their practical prospects in precise nutritional interventions.


Assuntos
Hidrogéis , Humanos , Hidrogéis/química , Sistemas de Liberação de Medicamentos , Medicina de Precisão , Disponibilidade Biológica , Polissacarídeos/química
20.
Carbohydr Polym ; 344: 122527, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39218534

RESUMO

The root of Millettia pulchra (YLS) has been traditionally used as a folk medicine for the treatment of depression and insomnia in the Zhuang nationality of China, and its polysaccharides have potential antidepressant effect. In this study, a novel homogeneous polysaccharide (YLP-1) was purified from the crude polysaccharides of YLS, and it is mainly composed of glucose, arabinose and mannose with molar ratio of 87.25%, 10.77%, and 1.98%, respectively. YLP-1 is a novel α-glucan with the backbone of 1,4-Glcp and branched at C6 of 1,4,6-Glcp to combine 1,4-Manp and 1,5-Araf. The microstructure of YLP-1 displayed a uniform ellipsoidal-like chain morphology and dispersed uniformly in solution. YLP-1 effectively ameliorated depression-like ethological behaviors and restored the decreased catecholamine levels in chronic variable stress (CVS)-induced depression rats. Additionally, it significantly improved the disturbance of gut microbiota induced by CVS stimuli, particularly affecting bacteria that produce short-chain fatty acids (SCFAs), such as bacteria species Lactobacillus spp.. In vitro fermentation study further confirmed that YLP-1 intake could promote SCFAs production by Lactobacillus spp. YLP-1 also mitigated the disruption of tryptophan metabolites in urine and serum. These findings provide evidences for the further development of YLP-1 as a macromolecular antidepressant drug.


Assuntos
Antidepressivos , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Millettia , Polissacarídeos , Triptofano , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/química , Masculino , Ratos , Polissacarídeos/farmacologia , Polissacarídeos/química , Millettia/química , Triptofano/metabolismo , Ácidos Graxos Voláteis/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Ratos Sprague-Dawley
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