RESUMEN
Glycosaminoglycans (GAGs) are valuable bioactive polysaccharides with promising biomedical and pharmaceutical applications. In this study, we analyzed GAGs using HPLC-MS/MS from the bone (B), muscle (M), skin (S), and viscera (V) of Scophthalmus maximus (SM), Paralichthysi (P), Limanda ferruginea (LF), Cleisthenes herzensteini (G), Platichthys bicoloratus (PB), Pleuronichthys cornutus (PC), and Cleisthenes herzensteini (CH). Unsaturated disaccharide products were obtained by enzymatic hydrolysis of the GAGs and subjected to compositional analysis of chondroitin sulfate (CS), heparin sulfate (HS), and hyaluronic acid (HA), including the sulfation degree of CS and HS, as well as the content of each GAG. The contents of GAGs in the tissues and the sulfation degree differed significantly among the fish. The bone of S. maximus contained more than 12 µg of CS per mg of dry tissue. Although the fish typically contained high levels of CSA (CS-4S), some fish bone tissue exhibited elevated levels of CSC (CS-6S). The HS content was found to range from 10-150 ug/g, primarily distributed in viscera, with a predominant non-sulfated structure (HS-0S). The structure of HA is well-defined without sulfation modification. These analytical results are independent of biological classification. We provide a high-throughput rapid detection method for tissue samples using HPLC-MS/MS to rapidly screen ideal sources of GAG. On this basis, four kinds of CS were prepared and purified from flounder bone, and their molecular weight was determined to be 23-28 kDa by HPGPC-MALLS, and the disaccharide component unit was dominated by CS-6S, which is a potential substitute for CSC derived from shark cartilage.
Asunto(s)
Sulfatos de Condroitina , Lenguado , Glicosaminoglicanos , Espectrometría de Masas en Tándem , Animales , Sulfatos de Condroitina/química , Sulfatos de Condroitina/aislamiento & purificación , Glicosaminoglicanos/aislamiento & purificación , Glicosaminoglicanos/química , Cromatografía Líquida de Alta Presión , Huesos/química , Piel/química , Piel/metabolismo , Ácido Hialurónico/química , Ácido Hialurónico/aislamiento & purificación , Músculos/químicaRESUMEN
Previous studies have demonstrated that the intestinal abundance of Bacteroides uniformis is significantly higher in healthy controls than that in patients with ulcerative colitis (UC). However, what effect B. uniformis has on the development of UC has not been characterized. Here, we show for the first time that B. uniformis F18-22, an alginate-fermenting bacterium isolated from the healthy human colon, protects against dextran-sulfate-sodium (DSS)-induced UC in mice. Specifically, oral intake of B. uniformis F18-22 alleviated colon contraction, improved intestinal bleeding and attenuated mucosal damage in diseased mice. Additionally, B. uniformis F18-22 improved gut dysbiosis in UC mice by increasing the abundance of anti-inflammatory acetate-producing bacterium Eubacterium siraeum and decreasing the amount of pro-inflammatory pathogenetic bacteria Escherichia-Shigella spp. Moreover, B. uniformis F18-22 was well-tolerated in mice and showed no oral toxicity after repeated daily administration for 28 consecutive days. Taken together, our study illustrates that B. uniformis F18-22 is a safe and novel probiotic bacterium for the treatment of UC from the healthy human colon.
Asunto(s)
Colitis Ulcerosa , Colitis , Probióticos , Humanos , Animales , Ratones , Colitis Ulcerosa/microbiología , Colon/patología , Bacteroides , Probióticos/uso terapéutico , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Colitis/patologíaRESUMEN
Porphyran and its derivatives possess a variety of biological activities, such as ameliorations of oxidative stress, inflammation, hyperlipemia, and immune deficiencies. In this study, we evaluated the potential efficacy of porphyran-derived oligosaccharides from Porphyra yezoensis (PYOs) in alleviating nonalcoholic fatty liver disease (NAFLD) and preliminarily clarified the underlying mechanism. NAFLD was induced by a high-fat diet for six months in C57BL/6J mice, followed by treatment with PYOs (100 or 300 mg/kg/d) for another six weeks. We found that PYOs reduced hepatic oxidative stress in mice with NAFLD, which plays a critical role in the occurrence and development of NAFLD. In addition, PYOs could markedly decrease lipid accumulation in liver by activating the IRS-1/AKT/GSK-3ß signaling pathway and the AMPK signaling pathway in mice with NAFLD. PYOs also apparently relieved the hepatic fibrosis induced by oxidative stress via downregulation of TGF-ß and its related proteins, so that liver injury was markedly alleviated. Furthermore, PYOs treatment relieved cecal microbiota dysbiosis (such as increasing the relative abundance of Akkermansia, while decreasing the Helicobacter abundance), which could alleviate oxidative stress, inflammation, and lipid metabolism, and protect the liver to a certain degree. In summary, PYOs treatment remarkably improved NAFLD via a specific molecular mechanism and reshaped the cecal microbiota.
Asunto(s)
Ciego/efectos de los fármacos , Modelos Animales de Enfermedad , Disbiosis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Oligosacáridos/farmacología , Sefarosa/análogos & derivados , Animales , Ciego/microbiología , Disbiosis/complicaciones , Disbiosis/microbiología , Metabolismo de los Lípidos , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/patología , Oligosacáridos/química , Estrés Oxidativo , Sefarosa/química , Transducción de SeñalRESUMEN
The unique living environment of marine microorganisms endows them with the potential to produce novel chemical compounds with various biological activities. Among them, the exopolysaccharides produced by marine microbes are an important factor for them to survive in these extreme environments. Up to now, exopolysaccharides from marine microbes, especially from extremophiles, have attracted more and more attention due to their structural complexity, biodegradability, biological activities, and biocompatibility. With the development of culture and separation methods, an increasing number of novel exopolysaccharides are being found and investigated. Here, the source, structure and biological activities of exopolysaccharides, as well as their potential applications in environmental restoration fields of the last decade are summarized, indicating the commercial potential of these versatile EPS in different areas, such as food, cosmetic, and biomedical industries, and also in environmental remediation.
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Polisacáridos Bacterianos , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/farmacologíaRESUMEN
Polysaccharide from the edible alga Enteromorpha clathrata has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we illustrate that Enteromorpha clathrata polysaccharide (ECP) could alleviate body weight loss, reduce incidences of colonic bleeding, improve stool consistency and ameliorate mucosal damage in diseased mice. 16S rRNA high-throughput sequencing and bioinformatic analysis indicated that ECP significantly changed the structure of the gut microbiota and increased the abundance of Parabacteroides spp. in DSS-fed mice. In vitro fermentation studies further confirmed that ECP could promote the growth of Parabacteroides distasonis F1-28, a next-generation probiotic bacterium isolated from the human gut, and increase its production of short-chain fatty acids. Additionally, Parabacteroides distasonis F1-28 was also found to have anti-ulcerative colitis effects in DSS-fed mice. Altogether, our study demonstrates for the first time a beneficial effect of ECP on ulcerative colitis and provides a possible basis for understanding its therapeutic mechanisms from the perspective of symbiotic gut bacteria Parabacteroides distasonis.
Asunto(s)
Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Humanos , Animales , Ratones , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/microbiología , Sulfato de Dextran/toxicidad , ARN Ribosómico 16S , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Bacterias , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Colon/microbiologíaRESUMEN
To investigate the effect of eupatilin in asthma treatment, we evaluated its therapeutic effect and related signal transduction in OVA-induced asthmatic mice and LPS-stimulated RAW264.7 cells. The BALF was tested for changes in lung inflammatory cells. Th2 cytokines in the BALF and OVA-IgE in the serum were measured by ELISA. H&E and PAS staining were used to evaluate histopathological changes in mouse lungs. The key proteins NF-κB, MAPK, and Nrf2 in lung tissues were quantitatively analyzed by Western blotting. Finally, we evaluated the effect of eupatilin on cytokines and related protein expression in LPS-stimulated RAW 264.7 cells in vitro. In OVA-induced asthmatic mice, eupatilin reduced the numbers of inflammatory cells, especially neutrophils and eosinophils. Eupatilin also decreased the levels of IL-5, IL-13 in the BALF and OVA-IgE in the serum. Furthermore, eupatilin inhibited the activation of NF-κB and MAPK pathways and increased the expression of Nrf2 in OVA-induced asthmatic mice. In vitro, eupatilin significantly reduced LPS-stimulated NO, IL-6, and ROS production. Additionally, the NF-κB, MAPK, and Nrf2 protein expression in LPS-stimulated RAW264.7 cells was consistent with that in OVA-induced asthmatic lung tissues. In summary, eupatilin attenuated OVA-induced asthma by regulating NF-κB, MAPK, and Nrf2 signaling pathways. These results suggest the utility of eupatilin as an anti-inflammatory drug for asthma treatment.
Asunto(s)
Asma/tratamiento farmacológico , Flavonoides/administración & dosificación , Lipopolisacáridos/efectos adversos , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Ovalbúmina/efectos adversos , Animales , Asma/inducido químicamente , Asma/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Modelos Animales de Enfermedad , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Femenino , Flavonoides/química , Flavonoides/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/inmunología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Estructura Molecular , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Ovalbúmina/inmunología , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The underlying mechanisms of circular RNAs (circRNAs) in lipid metabolism regulation and the pathogenesis of lipid disorder diseases are clarified in this review. circRNAs are produced from host genes by back splicing and are mainly degraded by RNase L. circRNAs act as molecular sponges or scaffolds that bind with microRNAs or proteins and thus affect the intracorporeal processes of lipid metabolism. CircRNA_11897 and circSAMD4A facilitated adipogenesis while circH19 and circRNA_26852 accelerated adipolysis in adipose tissue. CircSAMD4A promoted the differentiation of preadipocytes, but circH19 and circFUT10 inhibited this differentiation. CircFUT10 also promoted the proliferation of preadipocytes. CiRS-133 fostered the browning of white adipose tissue. CircACC1, circRNA_021412, circRNA_0046366, and circRNA_0046367 promoted the mitochondrial ß-oxidation of fatty acids in hepatocytes. CircRNA_021412 suppressed the synthesis of triglycerides in hepatocytes. CircScd1 inhibited hepatic lipid droplet formation. circ_0092317, circ_0003546, circ_0028198, circ_0092317, and circACC1 probably reduced cholesterol efflux from macrophages. circ_0037251 likely promoted lipid accumulation and inhibited lipophagy in macrophages. circRNAs participate in lipid metabolism regulation and affect the development of lipid disorder diseases.
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Adipogénesis/genética , Diferenciación Celular/genética , Metabolismo de los Lípidos/genética , MicroARNs/genética , ARN Circular/genética , Adipocitos/citología , Tejido Adiposo/metabolismo , Proliferación Celular/genética , Colesterol/metabolismo , Hepatocitos/metabolismo , Humanos , Macrófagos/metabolismoRESUMEN
Campylobacter jejuni is the leading cause of human diarrheal diseases and has been designated as one of highly resistant pathogens by the World Health Organization. The C. jejuni capsular polysaccharides feature broad existence of uncommon 6dHepp residues and have proven to be potential antigens to develop innovative antibacterial glycoconjugation vaccines. To address the lack of synthetic methods for rare 6dHepp architectures of importance, we herein describe a novel and efficient approach for the preparation of uncommon d-/l-6dHepp fluorides that have power as glycosylating agents. The synthesis is achieved by a C1-to-C5 switch strategy relying on radical decarboxylative fluorination of uronic acids arising from readily available allyl d-C-glycosides. To further showcase the application of this protocol, a structurally unique hexasaccharide composed of â3)-ß-d-6didoHepp-(1â4)-ß-d-GlcpNAc-(1â units, corresponding to the capsular polysaccharide of C. jejuni strain CG8486 has been assembled for the first time. The assembly is characterized by highly efficient construction of the synthetically challenging ß-(1,2-cis)-d-ido-heptopyranoside by inversion of the C2 configuration of ß-(1,2-trans)-d-gulo-heptopyranoside, which is conveniently obtained by anchimerically assisted stereoselective glycosylation of the orthogonally protected 6dgulHepp fluoride. Ready accessibility of 6dHepp fluorides and the resulting glycans could serve as a rational starting point for the further development of synthetic vaccines fighting Campylobacter infection.
Asunto(s)
Campylobacter jejuni/química , Fluoruros/síntesis química , Polisacáridos Bacterianos/química , Piranos/síntesis química , Conformación de Carbohidratos , Fluoruros/química , Glicosilación , Piranos/químicaRESUMEN
The development of neuromorphic computation faces the appreciable challenge of implementing hardware with energy consumption on the level of a femtojoule per synaptic event to be comparable with the energy consumption of human brain. Controllable ultrathin conductive filaments are needed to achieve such extremely low energy consumption in memristive synapses but their formation is difficult to control owing to their stochastic morphology and unexpected overgrowth. Herein, a zeolite-based memristive synapse is demonstrated for the first time, in which Ag exchange in the sub-nanometer pore closely resembles synaptic Ca2+ dynamics across biomembrane channel. Particularly, the confined ultrasmall pore and low Ag ion migration barrier give the zeolite-based memristive synapse ultralow energy consumption below 10 fJ per synaptic spike, on par with the biological counterpart. Experimental results reveal that the gradual memristive effect is attributed to the dimension modulation of Ag clusters. In addition to emulating inherent cognitive functions through electrical stimulations, the experience-dependent transition of short-term plasticity to long-term plasticity using a chemical modulation method is achieved by treating the initial Ag quantity as a learning experience. The proposed memristors can be used to develop highly efficient memristive neural networks and are considered as a candidate for application in neuromorphic computation.
Asunto(s)
Zeolitas , Encéfalo , Conductividad Eléctrica , Humanos , Redes Neurales de la Computación , SinapsisRESUMEN
Mucins are the major proteins that distributed on the intestinal mucosa layer and protect the intestine from pathogens infection. The composition of intestinal mucin O-glycans can affect the health of the gastrointestinal tract in pigs. Porcine intestinal mucosa is widely used as the main raw material of heparin extraction. The heparin extraction residues rich in mucins were usually wasted. The structure of mucin derived O-glycans in porcine intestinal mucosa are currently unknown. In this study, we isolated the mucins from the heparin extraction residues and profiled the O-glycans. After heparin extraction, mucin was digested with trypsin, and separated by strong anion exchange chromatography. The mucin derived O-glycans were release by alkaline ß elimination, and analyzed by ultra high performance liquid chromatography-porous graphitized carbon-Fourier transform mass spectrometry (UPLC-PGC-FTMS/MS). Thirty five kinds of O-glycans were identified, most of which were Core 3-derived glycans. In particular, the O-glycans containing sialic acid Neu5Ac accounted for 71.93% of the total O-glycans, which were different from that of other species, including mouse intestine, fish intestine, and porcine colon. The high content sialylated mucin may explain its effect in biological processes. Furthermore, the immunological activity results indicated that the porcine intestinal mucin could promote phagocytosis and proliferation without any cytotoxic effects, which may aid in the development of immunomodulators.
Asunto(s)
Heparina/química , Mucosa Intestinal/química , Mucosa Intestinal/metabolismo , Macrófagos/efectos de los fármacos , Mucinas/química , Mucinas/farmacología , Animales , Heparina/metabolismo , Macrófagos/inmunología , Ratones , Células RAW 264.7 , PorcinosRESUMEN
Heparin and its derivative are commonly used as injectable anticoagulants in clinical procedures, but possess poor oral bioavailability. To explore the role of gut microbiota in the poor oral effect of heparin, the degradation profiles of heparin on six human gut microbiota were investigated. The heparin-degradation ability varied significantly among individuals. Furthermore, two strains of heparin-degrading bacteria, Bacteroides ovatus A2 and Bacteroides cellulosilyticus B19, were isolated from the gut microbiota of different individuals and the degradation products of the isolates were profiled. The ΔUA2S-GlcNS6S was the major end product with almost no desulfation. 3-O-sulfo group-containing tetrasaccharides were detected, which indicated that the antithrombin binding site was broken and this explained the lost anticoagulant activity of heparin. Collectively, the present study assessed the degradation profiles of heparin by human gut microbiota and provided references for the development of oral administration of heparin from a gut microbiota perspective.
Asunto(s)
Bacteroides/metabolismo , Microbioma Gastrointestinal , Heparina/metabolismo , Adulto , Bacteroides/aislamiento & purificación , Heces/microbiología , Femenino , Fermentación , Heparina/química , Humanos , Masculino , Adulto JovenRESUMEN
The constant outbreak of diseases caused by viral infections has caused serious harm to human health all over the world. Although many antiviral drugs have been approved for clinical use during the past decade, important issues, such as unsatisfactory efficacy, toxicity, and high cost of drugs, remain unresolved. Glycans are major components of the surfaces of both host cells and most viruses and play critical roles in the steps of viral infection. Marine glycans have more structural diversities than those found in humans. Most importantly, low toxicity and low-cost marine glycans have demonstrated potent antiviral activities through multiple molecular mechanisms. As a result, a series of marine glycan-derived agents are undergoing preclinical and clinical trials. This review discusses the recent progress in research on the marine glycan-based antiviral agents in clinical trials, relating to their structural features and clinical applications. In addition, molecular mechanisms of marine glycans involved in viral infection and novel strategies used in glycan-based drug development are critically reviewed and discussed.
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Antivirales/aislamiento & purificación , Antivirales/uso terapéutico , Organismos Acuáticos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/uso terapéutico , Animales , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , HumanosRESUMEN
We previously demonstrated that fucoidan with a type II structure inhibited postprandial hyperglycemia by suppressing glucose uptake, but the mechanism remains elusive. Here, we aimed to assess whether the effect of glucose absorption inhibition was related to the basic structure of fucoidans and preliminarily clarified the underlying mechanism. Fucoidans with type II structure and type I structure were prepared from Ascophyllumnodosum (AnF) or Laminariajaponica (LjF) and Kjellmaniellacrassifolia (KcF), respectively. The effects of various fucoidans on suppressing postprandial hyperglycemia were investigated using in vitro (Caco-2 monolayer model), semi-in vivo (everted gut sac model), and in vivo (oral glucose tolerance test, OGTT) assays. The results showed that only AnF with a type II structure, but not LjF or KcF with type I structure, could inhibit the glucose transport in the Caco-2 monolayer and everted gut sac models. A similar result was seen in the OGTT of Kunming mice and leptin receptor-deficient (db/db) mice, where only AnF could effectively inhibit glucose transport into the bloodstream. Furthermore, AnF (400 mg/kg/d) treatment decreased the fasting blood glucose, HbA1c, and fasting insulin levels, while increasing the serum glucagon-like peptide-1 (GLP-1) level in obese leptin receptor-deficient (db/db) mice. Furthermore, surface plasmon resonance (SPR) analysis revealed the specific binding of AnF to Na+/glucose cotransporter 1 (SGLT1), which indicated the effect of AnF on postprandial hyperglycemia could be due to its suppression on SGLT1 activity. Taken together, this study suggests that AnF with a type II structure can be a promising candidate for hyperglycemia treatment.
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Ascophyllum/química , Hiperglucemia/prevención & control , Polisacáridos/farmacología , Transportador 1 de Sodio-Glucosa/antagonistas & inhibidores , Animales , Glucemia/metabolismo , Células CACO-2 , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Laminaria/química , Masculino , Ratones , Ratones Endogámicos C57BL , Phaeophyceae/química , Polisacáridos/aislamiento & purificaciónRESUMEN
This study aimed to show the α-L-Hexaguluroic acid hexasodium salt (G6) protective effect against UVA-induced photoaging of human keratinocyte cells. We found that G6 localized to the mitochondria and improved mitochondrial functions. G6 increased respiratory chain complex activities, which led to increased cellular ATP content and NAD+/NADH ratio. Thus, G6 alleviated the oxidative stress state in UVA-irradiated cells. Moreover, G6 can regulate the SIRT1/pGC-1α pathway, which enhanced the cells' viability and mitochondria energy metabolism. Notably, the anti-photoaging potential of G6 was directly associated with the increased level of MMP and SIRT1, which was followed by the upregulation of pGC-1α, D-LOOP, and Mt-TFA, and with the transcriptional activation of NRF1/NRF2. Taking all of the results together, we conclude that G6 could protect HaCaT cells from UVA-induced photo-aging via the regulation of mitochondria energy metabolism and its downstream signaling pathways.
Asunto(s)
Ácidos Hexurónicos/farmacología , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Protectores Solares/farmacología , Adenosina Trifosfato/metabolismo , Línea Celular , Ácidos Hexurónicos/química , Humanos , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo , Protectores Solares/química , Rayos Ultravioleta/efectos adversosRESUMEN
Aberrant protein glycosylation is observed in the progression of many types of diseases, including different cancers. In this study, we assess differential N-glycan patterns of human breast cancer cells and tissues by PGC-ESI-MS/MS. Compared with mammary epithelial cells, high-mannose glycans were significantly elevated in breast cancer cells. However, the alteration of N-glycans in tissues was more obvious than that in cells. Sixty-three kinds of different N-glycans were stably identified, and 38 types of them exhibited significant differences between para-carcinoma and breast cancer tissues. High-mannose glycans and core-fucosylated glycans were increased in the breast cancer tissues, while bisected glycans and sialylated glycans were decreased. Moreover, a total of 27 types of N-glycans displayed evident differences between benign breast tumor and breast cancer tissues, and most of them including bisected and sialylated glycans exhibited decreased relative abundances in cancer tissues. Overall, three high-mannose N-glycans (F0H6N2S0, F0H7N2S0, F0H8N2S0) exhibited significant diagnostic accuracy in both breast cancer cells and tissues, suggesting their potential role in biomarkers. Furthermore, a negative correlation between sialylated glycans and age of patients was identified. In conclusion, our results may be beneficial to understand the role that N-glycan plays on the progression of breast cancer and propose potential diagnostic biomarkers.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Neoplasias/diagnóstico , Polisacáridos/genética , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Glicosilación , Humanos , Glándulas Mamarias Humanas/metabolismo , Glándulas Mamarias Humanas/patología , Manosa/química , Persona de Mediana Edad , Neoplasias/genética , Neoplasias/patología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
Gangliosides altered during the pathological conditions and particularly in cancers. Here, we aimed to profile the gangliosides in breast cancer serum and propose potential biomarkers. LC-FTMS method was first used to identify all the ganglioside species in serum, then LC-MS/MS-MRM method was employed to quantitate the levels of gangliosides in serum from healthy volunteers and patients with benign breast tumor or breast cancer. 49 ganglioside species were determined, including GM1, GM2, GM3, GD1, GD3 and GT1 species. Compared to healthy volunteers, the levels of GM1, GM2, GM3, GD1 and GD3 displayed a rising trend in breast cancer patients. In particular, as the major glycosphingolipid component, GM3 showed excellent diagnostic accuracy in cancer serum (AUC > 0.9). PCA profile of the GM3 species showed clear distinction between normal and cancer serum. What's more, ROC curve proved great diagnostic accuracy of GM3 between cancer and benign serum. In addition, GM3 was discovered as a diagnostic marker to differentiate luminal B subtype from other subtypes. Furthermore, a positive correlation between GM3 and Ki-67 status of patients was identified. In conclusion, our results introduced the alteration patterns of serum gangliosides in breast cancer and suggested serum GM3 as a potential diagnostic biomarker in breast cancer diagnosis and luminal B subtype distinction.
Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Gangliósido G(M3)/sangre , Neoplasias/diagnóstico , Adulto , Anciano , Área Bajo la Curva , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Cromatografía Liquida , Diagnóstico Diferencial , Femenino , Gangliósidos/sangre , Gangliósidos/clasificación , Humanos , Antígeno Ki-67/sangre , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/patología , Análisis de Componente Principal , Pronóstico , Curva ROC , Espectrometría de Masas en TándemRESUMEN
Fucosylated chondroitin sulfate (fCS), a representative marine polysaccharide isolated from sea cucumber, possesses diverse biological functions especially as a promising anticoagulant. However, its supply suffers from the challenges of high-cost materials, different species, and batch-to-batch variability. In the present study, we designed a concise route for the synthesis of functional glycomimetics by natural fCS as a template. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated amidation was applied on chondroitin sulfates for site-selective alkynylation with controllable ratios between 0.15 and 0.78. A small library of 12 fCS glycomimetics with specific sulfation patterns and fucose branches was prepared through copper-catalyzed azide-alkyne cycloaddition, which was fully characterized by nuclear magnetic resonance spectroscopy and size-exclusion chromatography with multiangle light scattering and refractive index. Through screening of their biological activities, CSE-F1 and CSE-SF1 exhibited anticoagulant activities through intrinsic pathway and inhibition of factor Xa by antithrombin III. The concise approach developed herein supplies novel glycopolymers to mimic the distinct functions of natural polysaccharides and promote the development of marine carbohydrate-based drugs.
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Anticoagulantes/síntesis química , Materiales Biomiméticos/síntesis química , Sulfatos de Condroitina/química , Química Clic/métodos , Fucosa/químicaRESUMEN
The first example of metallic bismuth encapsulated into a mesoporous metal-organic framework of the type MIL-101(Cr) matrix is presented. Bi(III)-impregnated MIL-101(Cr) (Bi(III)/MIL-101(Cr)) was dropped onto a conductive carbon cloth electrode (CCE). Then, bismuth was generated by electrochemical reduction of the Bi(III)/MIL-101(Cr) supported on CCE (Bi/MIL-101(Cr)/CCE). The resulting Bi/MIL-101(Cr)/CCE display impressive performance in terms of peak currents for the ions Cd(II) and Pb(II) when compared to the single-component counterparts. Differential pulse anodic stripping voltammetry (DPASV) enabled sensing of the two ions over linear working range of 0.1 to 30 µg L-1 and 30 to 90 µg L-1. The parameters are refined before the detection of two metal ions, including the amount of bismuth in MIL-101(Cr), optimum pH (5.0), deposition potential (-1.2 V) and deposition time (600 s). The respective detection limits are 60 and 70 ng L-1 (at S/N = 3). This is strikingly lower than the guideline values of domestic water given by the WHO which are 3 µg L-1 for Cd(II) and 10 µg L-1 for Pb(II). The Bi/MIL-101(Cr) onto CCE is fairly specific for Cd(II) (at around -0.76 V) and Pb(II) (at around -0.54 V), well reproducible and has excellent recovery in real water analysis. Graphical abstract Schematic illustration of the preparation of a Bi(III)/MIL-101(Cr) metal-organic framework, its deposition on a carbon cloth electrode (CCE), and its application for detection of Cd(II) and Pb(II) by differential pulse adsorptive stripping voltammetry (DPASV).
RESUMEN
Intestinal mucins constitute the major component of the mucus covering the epithelium of the gastrointestinal tract, thereby forming a barrier against microbial colonization. Rabbits are bred in large numbers worldwide, with little known about intestinal O-glycosylation despite this insight being crucial to the understanding of host-pathogen interactions. In the present study, a major mucin-type glycopeptide (RIF6) of hyla rabbit intestine was isolated and the O-glycans were extensively characterized based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with bioinformatics approaches. Thirty-three O-glycans were identified, and most of them were sulfated or sialylated glycans. It was worth noting that Neu5Gc-containing structures within sialylated O-glycans accounted for 91%, which were extremely different from that of other species including humans, mice, chickens, etc. Sulfated glycans accounted for 58%, unique disufated and sulfated-sialylated glycans were also detected in rabbit intestinal mucin. These structural characterization reflected species diversity and may provide deeper insights into explaining the adaptability of hyla rabbit to the environment.
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Metaboloma , Metabolómica , Mucinas/química , Ácidos Neuramínicos/química , Polisacáridos/química , Sulfatos/química , Animales , Cromatografía Liquida , Fucosa/química , Tracto Gastrointestinal/metabolismo , Metabolómica/métodos , Mucinas/aislamiento & purificación , Mucinas/metabolismo , Ácidos Neuramínicos/metabolismo , Polisacáridos/metabolismo , Conejos , Relación Estructura-Actividad , Espectrometría de Masas en TándemRESUMEN
Recent studies have reported that dietary fiber improved metabolic syndrome (MetS). However, the effects of fucoidans on MetS were still not clear. In this study, we evaluated the activity of fucoidan from Fucus vesiculosus (FvF) on attenuating MetS and first elucidated the underlying mechanism. In vitro, FvF treatment remarkably lowered the level of reactive oxygen species (ROS) compared with the sodium palmitate (PA)-induced insulin resistance (IR) group. The phosphorylation level of c-Jun N-terminal kinase (JNK) was significantly decreased, while phosphorylation of protein kinase B (pAkt) level increased, compared with that of the HepG2 cells treated with PA. Thus, FvF increased glucose consumption and relieved IR via ROS-mediated JNK and Akt signaling pathways. In addition, these changes were accompanied by the activation of adenosine 5'-monophosphate-ativated protein kinase (AMPK) and its downstream targets (e.g., HMG-CoA reductase (HMGCR), acetyl-CoA carboxylase (ACC), and sterol-regulatory element-binding protein-1c (SREBP-1C)), which improved lipid metabolism in IR HepG2 cells. In vivo, FvF improved hyperglycemia and decreased serum insulin level in mice with MetS. Furthermore, we evaluated the inhibition of glucose transport by in vitro (Caco-2 monolayer model), semi-in vivo (everted gut sac model) and oral glucose tolerance test (OGTT), which indicated that FvF could significantly reduce the absorption of glucose into the blood stream, thus it could improve blood-glucose levels and IR in mice with MetS. Moreover, FvF decreased serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels and liver lipid accumulation, while increased the serum high density lipoprotein cholesterol (HDL-C) level in mice with MetS. Therefore, FvF could be considered as a potential candidate for the treatment of MetS by alleviating IR, inhibiting glucose transportation, and regulating lipid metabolism.