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1.
Biomaterials ; 291: 121865, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36332287

RESUMEN

OBJECTIVE: While lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis. METHODS AND RESULTS: We found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-κB subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-κB pathway activation in endothelial cells by TNF-α. We treated ApoE-/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE-/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. In addition, there was a marked reduction in inflammation for female mice in the liver and aortic root in comparison to male mice. CONCLUSIONS: Rhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-κB, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE-/- mice.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Masculino , Femenino , Ratones , Animales , Placa Aterosclerótica/tratamiento farmacológico , FN-kappa B/metabolismo , Células Endoteliales/metabolismo , Sulfatos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Apolipoproteínas E/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratones Endogámicos C57BL
2.
Carbohydr Polym ; 285: 119250, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35287864

RESUMEN

A pectic polysaccharide (WAP) was isolated from squash and identified as a homogalacturonan with a molecular mass of 83.2 kDa by GPC, monosaccharide composition analysis, FT-IR and NMR spectra. Sulfation modification of WAP was carried out and a sulfated derivative (SWAP) was obtained with a substitution degree of 1.81. The NMR spectrum indicated that the sulfation modification mainly occurred at the C-2 and C-3 positions of galacturonan residues. The binding pattern of SWAP to tau K18 protein was observed in 2D 1H15N HSQC spectra of tau, which resembled the tau-heparin interaction, with R2 domain as the major binding region. These results suggest that SWAP has the potential to act as a heparin mimic to inhibit the transcellular spread of tau; thus natural polysaccharide from squash may be developed into therapies for AD and related tauopathies.


Asunto(s)
Pectinas , Sulfatos , Heparina/química , Espectroscopía Infrarroja por Transformada de Fourier , Sulfatos/química
3.
Food Chem ; 383: 132387, 2022 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-35182862

RESUMEN

To characterize the structure of purified raspberry pectin and discuss the impact of different extraction methods on the pectin structure, raspberry pectin was extracted by hot-acid and enzyme method and purified by stepwise ethanol precipitation and ion-exchange chromatography isolation. Enzyme-extracted raspberry pectin (RPE50%-3) presented relatively intact structure with molecular weight of 5 × 104 g/mol and the degree of methylation was 39%. The 1D/2D NMR analysis demonstrated RPE50%-3 was a high-branched pectin mainly containing 50% homogalacturonan, 16% branched α-1,5-arabinan and α-1,3-arabinan, 18% ß-1,4-galactan and ß-1,6-galactan. Acid-extracted raspberry pectin (RPA50%-3) contained less arabinan than RPE50%-3. Moreover, RPE50%-3 inhibited the nitric oxide (NO), TNF-α, IL-6 production of lipopolysaccharide-induced macrophages by 67%, 22% and 46% at the dosage of 200 ug/mL, while the inhibitory rate of RPA50%-3 were 33%, 9%, and 1%, respectively. These results suggested that enzyme-extracted raspberry pectin contained more arabinan sidechains and exhibited better immunomodulatory effect.


Asunto(s)
Rubus , Antiinflamatorios/farmacología , Galactanos/química , Peso Molecular , Pectinas/química , Polisacáridos/química
4.
Mar Drugs ; 19(12)2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34940684

RESUMEN

The COVID-19 pandemic is a major human health concern. The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor. Our previous studies demonstrated that sulfated glycans, such as heparin and fucoidans, show anti-COVID-19 activities. In the current study, rhamnan sulfate (RS), a polysaccharide with a rhamnose backbone from a green seaweed, Monostroma nitidum, was evaluated for binding to the S-protein from SARS-CoV-2 and inhibition of viral infectivity in vitro. The structural characteristics of RS were investigated by determining its monosaccharide composition and performing two-dimensional nuclear magnetic resonance. RS inhibition of the interaction of heparin, a highly sulfated HS, with the SARS-CoV-2 spike protein (from wild type and different mutant variants) was studied using surface plasmon resonance (SPR). In competitive binding studies, the IC50 of RS against the S-protein receptor binding domain (RBD) binding to immobilized heparin was 1.6 ng/mL, which is much lower than the IC50 for heparin (~750 ng/mL). RS showed stronger inhibition than heparin on the S-protein RBD or pseudoviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, RS showed strong antiviral activities against wild type SARS-CoV-2 and the delta variant.


Asunto(s)
Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Desoxiazúcares/farmacología , Mananos/farmacología , Extractos Vegetales/farmacología , SARS-CoV-2/efectos de los fármacos , Algas Marinas , Antivirales/uso terapéutico , Organismos Acuáticos , Desoxiazúcares/uso terapéutico , Humanos , Mananos/uso terapéutico , Extractos Vegetales/uso terapéutico , Unión Proteica/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/efectos de los fármacos , Relación Estructura-Actividad
5.
Carbohydr Polym ; 270: 118377, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34364621

RESUMEN

Several studies are described that contribute to the systematic exploration of new aspects of digestion, fermentation, and biological activities of pectic polysaccharides (PPS) leading to a better understanding of prebiotics. Inflammatory bowel disease (IBD) is thought to be associated with the dysbacteriosis induced by different environmental agents in genetically susceptible persons. PPS are considered as an indispensable gut-microbiota-accessible carbohydrate that play a dominant role in maintaining gut microbiota balance and show a better effect in ameliorating IBD than some traditional prebiotics. The aim of this review is to summarize the fermentation characteristics of PPS, highlight its role in improving IBD, and propose a view that PPS may be a new and effective prebiotic.


Asunto(s)
Colitis/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Pectinas/administración & dosificación , Polisacáridos/administración & dosificación , Prebióticos/administración & dosificación , Animales , Línea Celular , Colitis/metabolismo , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/metabolismo , Digestión/efectos de los fármacos , Disbiosis/tratamiento farmacológico , Femenino , Fermentación , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Masculino , Ratones , Pectinas/metabolismo , Polisacáridos/metabolismo , Ratas
6.
Compr Rev Food Sci Food Saf ; 20(2): 2015-2039, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33594822

RESUMEN

Pectic substances, one of the cell wall polysaccharides, exist widespread in vegetables and fruits. A surge of recent research has revealed that pectic substances can inhibit gut inflammation and relieve inflammatory bowel disease symptoms. However, physiological functions of pectins are strongly structure dependent. Pectic substances are essentially heteropolysaccharides composed of homogalacturonan and rhamnogalacturonan backbones substituted by various neutral sugar sidechains. Subtle changes in the architecture of pectic substances may remarkably influence the nutritional function of gut microbiota and the host homeostasis of immune system. In this context, developing a structure-function understanding of how pectic substances have an impact on an inflammatory bowel is of primary importance for diet therapy and new drugs. Therefore, the present review has summarized the polycomponent nature of pectic substances, the activities of different pectic polymers, the effects of molecular characteristics and the underlying mechanisms of pectic substances. The immunomodulated property of pectic substances depends on not only the chemical composition but also the physical structure characteristics, such as molecular weight (Mw ) and chain conformation. The potential mechanisms by which pectic substances exert their protective effects are mainly reversing the disordered gut microbiota, regulating immune cells, enhancing barrier function, and inhibiting pathogen adhesion. The manipulation of pectic substances on gut health is sophisticated, and the link between structural specificity of pectins and selective regulation needs further exploration.


Asunto(s)
Frutas , Pectinas , Pared Celular , Polisacáridos , Verduras
7.
J Virol ; 95(3)2021 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-33173010

RESUMEN

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. Currently there is no vaccine, effective therapeutic, or prophylactic. As with other betacoronaviruses, attachment and entry of SARS-CoV-2 are mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin-converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third-generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in antiviral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH, and 6-O-desulfated enoxaparin with 50% inhibitory concentrations (IC50s) of 5.99 µg/liter, 1.08 mg/liter, 1.77 µg/liter, and 5.86 mg/liter, respectively. In summary, several sulfated polysaccharides show potent anti-SARS-CoV-2 activity and can be developed for prophylactic as well as therapeutic purposes.IMPORTANCE The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry. The SARS-CoV-2 spike glycoprotein (SGP) binds to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we report structure-based differences in antiviral activity and affinity to SGP for several sulfated polysaccharides, including both well-characterized FDA-approved drugs and novel marine sulfated polysaccharides, which can be developed for prophylactic as well as therapeutic purposes.


Asunto(s)
Antivirales/farmacología , Heparina/farmacología , SARS-CoV-2/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Animales , Antivirales/química , Antivirales/metabolismo , Evaluación Preclínica de Medicamentos , Enoxaparina/química , Enoxaparina/metabolismo , Enoxaparina/farmacología , Vectores Genéticos/genética , Células HEK293 , Heparina/química , Heparina/metabolismo , Heparitina Sulfato/metabolismo , Humanos , Concentración 50 Inhibidora , Lentivirus/genética , Estructura Molecular , Peso Molecular , Polisacáridos/química , Polisacáridos/metabolismo , Polisacáridos/farmacología , Unión Proteica , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Transducción Genética , Acoplamiento Viral/efectos de los fármacos
8.
AMB Express ; 10(1): 144, 2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32803432

RESUMEN

N-glycolyl chondroitin (Gc-CN) is a metabolite of N-glycolylneuraminic acid (Neu5Gc), a sialic acid that is commonly found in mammals, but not humans. Humans can incorporate exogenous Neu5Gc into their tissues from eating red meat. Neu5Gc cannot be biosynthesized by humans due to an evolutionary mutation and has been implicated in causing inflammation causing human diseases, such as cancer. The study Neu5Gc is important in evolutionary biology and the development of potential cancer biomarkers. Unfortunately, there are several limitations to detecting Neu5Gc. The elimination of Neu5Gc involves a degradative pathway leading to the incorporation of N-glycolyl groups into glycosaminoglycans (GAGs), such as Gc-CN. Gc-CN has been found in humans and in animals including mice, lamb and chimpanzees. Here, we present the biosynthesis of Gc-CN in bacteria by feeding chemically synthesized N-glycolylglucosamine to Escherichia coli. A metabolically engineered strain of E. coli K4, fed with glucose supplemented with GlcNGc, converted it to N-glycolylgalactosamine (GalNGc) that could then be utilized as a substrate in the chondroitin biosynthetic pathway. The final product, Gc-CN was converted to disaccharides using chondroitin lyase ABC and analyzed by liquid chromatography-tandem mass spectrometry with multiple reaction monitoring detection. This analysis showed the incorporation of GalNGc into the backbone of the chondroitin oligosaccharide.

9.
Carbohydr Polym ; 245: 116526, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32718630

RESUMEN

Rhamnogalacturonan I (RG-I) pectin are regarded as strong galectin-3 (Gal-3) antagonist because of galactan sidechains. The present study focused on discussing the effects of more structural regions in pectin on the anti-Gal-3 activity. The water-soluble pectin (WSP) recovered from citrus canning processing water was categorized as RG-I pectin. The controlled enzymatic hydrolysis was employed to sequentially remove the α-1,5-arabinan, homogalaturonan and ß-1,4-galactan in WSP. The Gal-3-binding affinity KD (kd/ka) of WSP and debranched pectins were calculated to be 0.32 µM, 0.48 µM, 0.56 µM and 1.93 µM. Moreover, based on the more sensitive cell line (MCF-7) model, the IC30 value of WSP was lower than these of modified pectins, indicating decreased anti-Gal-3 activity. Our results suggested that the total amount of neutral sugar sidechains, the length of arabinan and cooperation between HG and RG-I played important roles in the anti-Gal-3 activity of WSP, not the Gal/Ara ratio or RG-I/HG ratio. These results provided a new insight into structure-activity relationship of citrus segment membrane RG-I as a galectin-3 antagonist and a new functional food.


Asunto(s)
Proteínas Sanguíneas/antagonistas & inhibidores , Membrana Celular/química , Citrus/química , Galactanos/farmacología , Galectinas/antagonistas & inhibidores , Pectinas/química , Pectinas/farmacología , Proteínas Sanguíneas/metabolismo , Pared Celular/química , Frutas/química , Galectinas/metabolismo , Humanos , Hidrólisis , Células MCF-7 , Pectinas/metabolismo , Células Vegetales , Polisacáridos/química , Unión Proteica , Solubilidad , Relación Estructura-Actividad , Agua/química
10.
J Agric Food Chem ; 68(32): 8688-8701, 2020 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-32633953

RESUMEN

Obesity is associated with gut microbiome dysbiosis. Our previous research has shown that highly branched rhamnogalacturonan type I (RG-I)-enriched pectin (WRP, 531.5 kDa, 70.44% RG-I, Rha/(Gal + Ara) = 20) and its oligosaccharide with less branched RG-I [DWRP, 12.1 kDa, 50.29% RG-I, Rha/(Gal + Ara) = 6] are potential prebiotics. The present study is conducted to uncover the impact of the content, molecular size, and branch degrees of RG-I on the inhibiting effect of high-fat diet (HFD)-induced obesity. The commercial pectin (CP, 496.2 kDa, 35.77% RG-I, Rha/(Gal + Ara) = 6), WRP, and DWRP were orally administered to HFD-fed C57BL/6J mice (100 mg kg-1 d-1) to determine their individual effects on obesity. WRP significantly prevented bodyweight gain, insulin resistance, and inflammatory responses in HFD-fed mice. No obvious anti-obesity effect was observed in either CP or DWRP supplementation. A mechanistic study revealed that CP and DWRP could not enhance the diversity of gut microbiota, while WRP treatment positively modulated the gut microbiota of obese mice by increasing the abundance of Butyrivibrio, Roseburia, Barnesiella, Flavonifractor, Acetivibrio, and Clostridium cluster IV. Furthermore, WRP significantly promoted browning of white adipose tissues in HFD-fed mice, while CP and DWRP did not. WRP can attenuate the HFD-induced obesity by modulation of gut microbiota and lipid metabolism. Highly branched RG-I domain enrichment is essential for pectin mitigating against the HFD-induced obesity.


Asunto(s)
Obesidad/dietoterapia , Pectinas/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Dieta Alta en Grasa/efectos adversos , Microbioma Gastrointestinal , Humanos , Metabolismo de los Lípidos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/etiología , Obesidad/microbiología , Pectinas/química
11.
J Cell Physiol ; 235(10): 7496-7515, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32162324

RESUMEN

Noncollagenous proteins in the bone extracellular matrix, such as osteocalcin (OC) and osteopontin (OPN), inherent to evolution of bone as a skeletal tissue, are known to regulate bone formation and mineralization. However, the fundamental basis of this regulatory role remains unknown. Here, for the first time, we use mouse mesenchymal stem/stromal cells (MSC) lacking both OC and OPN to investigate the mechanistic roles of OC and OPN on the proliferation capacity and differentiation ability of MSC. We found that the loss of OC and OPN reduces stem cells self-renewal potential and multipotency, affects their differentiation into an osteogenic lineage, and impairs their angiogenic potential while maintaining chondrogenic and adipogenic lineages. Moreover, loss of OC and OPN compromises the extracellular matrix integrity and maturation, observed by an unexpected enhancement of glycosaminoglycans content that are associated with a more primitive skeletal connective tissue, and by a delay on the maturation of mineral species produced. Interestingly, exogenously supplemented OC and OPN were able to rescue MSC proliferative and osteogenic potential along with matrix integrity and mineral quality. Taken together, these results highlight the key contributions of OC and OPN in enhancing osteogenesis and angiogenesis over primitive connective tissue, and support a potential therapeutic approach based on their exogenous supplementation.


Asunto(s)
Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/fisiología , Neovascularización Fisiológica/fisiología , Osteocalcina/metabolismo , Osteogénesis/fisiología , Osteopontina/metabolismo , Adipogénesis/fisiología , Animales , Huesos/metabolismo , Huesos/fisiología , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Tejido Conectivo/metabolismo , Tejido Conectivo/fisiología , Matriz Extracelular/metabolismo , Ratones , Ratones Endogámicos C57BL , Morfogénesis/fisiología
12.
Molecules ; 25(4)2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-32093113

RESUMEN

Polysaccharides are considered to be the most important active substances in Goji. However, the structure of polysaccharides varies according to the extraction methods applied, and the solution used to prepare Goji polysaccharides (LBPs) were limited. Thus, it is important to clarify the connection between extraction methods and structure of Goji polysaccharide. In view of the complex composition of cell wall polysaccharides and the various forms of interaction, different extraction methods will release different parts of the cell wall. The present study compared the effects of different extraction methods, which have been used to prepare different types of plant cell wall polysaccharides based on various sources, on the structure of cell-wall polysaccharides from Goji, by the single separate use of hot water, hydrochloric acid (0.4%) and sodium hydroxide (0.6%), at both high and low temperatures. Meanwhile, in order to explore the limitations of single extraction, sequential extraction methods were applied. Structural analysis including monosaccharide analysis, GPC-MALLS, AFM and 1H-NMR suggested the persistence of more extensively branched rhamnogalacturonan I (RG-I) domains in the procedures involving low-temperature-alkali, while procedures prepared by high-temperature-acid contains more homogalacturonan (HG) regions and results in the removal of a substantial part of the side chain, specifically the arabinan. A kind of acidic heteropolysaccharide was obtained by hot water extraction. SEC-MALLS and AFM confirmed large-size polymers with branched morphologies in alkali-extracted polysaccharides. Our results provide new insight into the extraction of Goji polysaccharides, which differ from the hot water extraction used by traditional Chinese medicine.


Asunto(s)
Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Lycium/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular
13.
Int J Biol Macromol ; 150: 765-774, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32035956

RESUMEN

Ganoderma lucidum, commonly known as "Lingzhi" in Chinese, are well-known medicinal mushrooms. Lingzhi has been used in traditional Chinese herbal medicines for more than two thousand years. G. lucidum polysaccharides (GLPs) are present at high levels in G. lucidum cells and GLPs have molecular weights ranging from thousands to millions. GLPs have been widely studied for their various biological activities, such as antioxidant, antitumor, anti-inflammatory, antiviral, anti-diabetes, and immunomodulatory activities. The methods for GLPs extraction and characterization are mature, but the comprehensive research on the relationship between GLPs structure (i.e., molecular weight, tertiary structure, branching, substituents, and monosaccharide composition) and function is still quite limited. The aim of this review is to update and summarize the mechanisms of the various bioactive polysaccharides extracted from G. lucidum. The information presented on these bio-mechanisms should be valuable in the research and development of GLPs-derived therapeutics.


Asunto(s)
Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/uso terapéutico , Reishi/química , Animales , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antioxidantes/química , Antioxidantes/uso terapéutico , Antivirales/química , Antivirales/uso terapéutico , Conformación de Carbohidratos , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Factores Inmunológicos/química , Factores Inmunológicos/uso terapéutico , Relación Estructura-Actividad
14.
J Biomed Mater Res B Appl Biomater ; 108(5): 2153-2166, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31916699

RESUMEN

The clinical demand for tissue-engineered bone is growing due to the increase of non-union fractures and delayed healing in an aging population. Herein, we present a method combining additive manufacturing (AM) techniques with cell-derived extracellular matrix (ECM) to generate structurally well-defined bioactive scaffolds for bone tissue engineering (BTE). In this work, highly porous three-dimensional polycaprolactone (PCL) scaffolds with desired size and architecture were fabricated by fused deposition modeling and subsequently decorated with human mesenchymal stem/stromal cell (MSC)-derived ECM produced in situ. The successful deposition of MSC-derived ECM onto PCL scaffolds (PCL-MSC ECM) was confirmed after decellularization using scanning electron microscopy, elemental analysis, and immunofluorescence. The presence of cell-derived ECM within the PCL scaffolds significantly enhanced MSC attachment and proliferation, with and without osteogenic supplementation. Additionally, under osteogenic induction, PCL-MSC ECM scaffolds promoted significantly higher calcium deposition and elevated relative expression of bone-specific genes, particularly the gene encoding osteopontin, when compared to pristine scaffolds. Overall, our results demonstrated the favorable effects of combining MSC-derived ECM and AM-based scaffolds on the osteogenic differentiation of MSC, resulting from a closer mimicry of the native bone niche. This strategy is highly promising for the development of novel personalized BTE approaches enabling the fabrication of patient defect-tailored scaffolds with enhanced biological performance and osteoinductive properties.


Asunto(s)
Materiales Biocompatibles/química , Huesos/metabolismo , Matriz Extracelular/química , Poliésteres/química , Andamios del Tejido/química , Materiales Biocompatibles/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Matriz Extracelular/metabolismo , Células Madre Mesenquimatosas , Osteogénesis , Porosidad , Implantación de Prótesis , Ingeniería de Tejidos
15.
Crit Rev Food Sci Nutr ; 60(17): 2938-2960, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31607142

RESUMEN

Rhamnogalacturonan I (RG-I) pectin is composed of backbone of repeating disaccharide units →2)-α-L-Rhap-(1→4)-α-D-GalpA-(1→ and neutral sugar side-chains mainly consisting of arabinose and galactose having variable types of linkages. However, since traditional pectin extraction methods damages the RG-I structure, the characteristics and health effects of RG-I remains unclear. Recently, many studies have focused on RG-I, which is often more active than the homogalacturonan (HG) portion of pectic polysaccharides. In food products, RG-I is common to fruits and vegetables and possesses many health benefits. This timely and comprehensive review describes the many different facets of RG-I, including its dietary sources, history, metabolism and potential functionalities, all of which have been compiled to establish a platform for taking full advantage of the functional value of RG-I pectin.


Asunto(s)
Dieta Saludable , Frutas/química , Pectinas/farmacología , Verduras/química , Alimentos Funcionales , Humanos , Pectinas/metabolismo
16.
Food Funct ; 10(12): 7828-7843, 2019 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-31778135

RESUMEN

Rhamnogalacturonan-I (RG-I)-enriched pectin (WRP) was recovered from citrus processing water by sequential acid and alkaline treatments in a previous study. RG-I-enriched pectin was proposed as a potential supplement for functional food and pharmaceutical development. However, previous studies illustrated that favorable modulations of gut microbiota by RG-I-enriched pectin were based on in vitro changes in the overall microbial structure and the question of whether there is a structure-dependent modulation of gut microbiota remains largely enigmatic. In the present study, modulations of gut microbiota by commercial pectin (CP), WRP and its depolymerized fraction (DWRP) with different RG-I contents and Mw were compared in vivo. It was revealed by 16s rRNA high-throughput sequencing that WRP and DWRP mainly composed of RG-I modulated the gut microbiota in a positive way. DWRP significantly increased the abundance of prebiotic such as Bifidobacterium spp., Lactobacillus spp., while WRP increased SCFAs producers including species in Ruminococcaceae family. By maintaining a more balanced gut microbiota composition and enriching some SCFA producers, dietary WRP and DWRP also elevated the SCFA content in the colon. Collectively, our findings offer new insights into the structure-activity correlation of citrus pectin and provide impetus towards the development of RG-I-enriched pectin with small molecular weight for specific use in health-promoting prebiotic ingredients and therapeutic products.


Asunto(s)
Bacterias/metabolismo , Bifidobacterium/crecimiento & desarrollo , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Lactobacillus/crecimiento & desarrollo , Pectinas/farmacología , Extractos Vegetales/farmacología , Animales , Bacterias/efectos de los fármacos , Bifidobacterium/efectos de los fármacos , Citrus/química , Faecalibacterium/efectos de los fármacos , Faecalibacterium/crecimiento & desarrollo , Fermentación , Lactobacillus/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Pectinas/análisis , Extractos Vegetales/análisis , Prebióticos/análisis
17.
J Sci Food Agric ; 99(14): 6219-6226, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31250449

RESUMEN

BACKGROUND: Temperatures that special fat faces in a real environment fluctuate, thus, understanding the property changes of special fats under fluctuating temperatures will be helpful in guiding how to keep its high quality in the production and application process. Therefore, a comparative study was carried out on the storage stability of physical blend-based and interesterified blend-based special fats (PBSFs and IBSFs) and their oxidative stability, crystallization and physical properties were studied under fluctuating temperatures. RESULTS: The peroxide values of IBSFs and PBSFs were less than 10.0 mmol kg-1 after 4 weeks of storage, and IBSFs had better oxidative stability. There was little change in the solid fat content, and the hardness decreased when IBSFs and PBSFs were stored for 4 weeks. X-ray diffraction results indicated that PBSFs had only ß-crystal, but IBSFs had ß- and ß'-crystal after storage. Moreover, in IBSFs, the transformation from ß'- to ß-form in PS:RO-IBSF was more obvious than that in PS:SO-IBSF (PS, palm stearin; SO, soybean oil; RO, rapeseed oil) after 4 weeks of storage, and the good integrity of crystalline network in fast-frozen special fats during fluctuating temperature storage followed the order: IBSF > PBSF, PS:RO-PBSF > PS:SO-PBSF. CONCLUSION: The results suggest IBSF can better maintain its quality during fluctuating temperature storage than PBSF. © 2019 Society of Chemical Industry.


Asunto(s)
Grasas/química , Aceite de Brassica napus/química , Aceite de Soja/química , Triglicéridos/química , Cristalización , Esterificación , Almacenamiento de Alimentos , Oxidación-Reducción , Aceite de Palma/química , Temperatura , Difracción de Rayos X
18.
Chem Biol Interact ; 308: 279-287, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31150628

RESUMEN

The dose-dependent neuroprotective role of licorice-derived glycyrrhizin during subacute neuroterminal norepinephrine (NE) depletion was studied in rat brain. Experimental design included thirty 5-week-old male rats randomly divided into five groups. Compared to the saline-injected control group, the group receiving daily intraperitoneal injection of fusaric acid (FA; 5 mg/kg/b.w.) for 30 days showed pharmacological depletion of NE. The neuroprotective effects of three successively increasing oral doses of glycyrrhizin were examined in FA-treated rats. Neurochemical parameters and histo-/immunohistopathological changes in the hippocampus were examined. FA generated global hippocampal stress with altered neurobiochemical parameters, accompanied by immune-confirmed inflammatory tissue damage, and noticeable behavioral changes. Although glycyrrhizin after FA-induced intoxication did not correct the recorded drop in the NE level, it decreased the dopamine levels to control levels. Similarly, glycyrrhizin at a high dose restored the serotonin level to its normal value and blocked the FA-induced increase in the level of its metabolite, 5-hydroxyindoleacetic acid. The FA-induced rise in γ-aminobutyric acid (GABA) and histamine was alleviated after administration of a high dose of glycyrrhizin. This was accompanied by improvements in the bioenergetic status and neuronal regenerative capacity through recovery of ATP and brain-derived neurotrophic factor levels to the pre-intoxicated values. High doses of glycyrrhizin also ameliorated the FA-generated behavioral changes and oxidative damage, manifested by the reduction in the expression of cortical pro-apoptotic caspase 3 in the same group. This study suggests that glycyrrhizin can potentially mend most of the previously evoked neuronal damage induced by FA intoxication in the brain of an experimental rat model.


Asunto(s)
Corteza Cerebral/efectos de los fármacos , Ácido Glicirrínico/farmacología , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Norepinefrina/metabolismo , Acetilcolinesterasa/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Ácido Fusárico/toxicidad , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/patología , Síndromes de Neurotoxicidad/veterinaria , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Ácido gamma-Aminobutírico/metabolismo
19.
J Colloid Interface Sci ; 538: 1-14, 2019 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-30481653

RESUMEN

A thermo-responsive amphiphile was developed from oligo-phenylalanine [oligo(Phe)]. The hydrophobic moiety of the amphiphile, oligo(Phe) was synthesized via reverse hydrolysis catalyzed by bromelain in dimethyl sulfoxide and dioxane solutions. The production of oligo(Phe) increased by 80.7% by screening suitable reaction conditions. The average degree of polymerization of oligo(Phe) was determined to be four by 1H NMR. By grafting with aldehyde-ended methoxypolyethylene glycol (mPEG), oligo(Phe) was converted to amphiphilic oligo(Phe)-mPEG. The surface tension of oligo(Phe)-mPEG solution increased with decreasing chain length of the mPEG moiety. Cytotoxicity studies showed oligo(Phe)-mPEGs are biocompatible. On varying temperature, a reversible phase transition of oligo(Phe)-mPEG solutions could be observed. N-octane-in-water emulsions and 0.5% beta-carotene containing squalene-in-water emulsions stabilized by oligo(Phe)-mPEGs occurred at 25 °C but de-emulsification took place at >40 °C. Emulsification could be restored once the separated mixture cooled and re-homogenized. The emulsification/de-emulsification cycling could be repeated many times. The time required for de-emulsification decreased with elevated temperature but increased with a reduced concentration of oligo(Phe)-mPEGs and a reduction in the chain length of the mPEG moiety.


Asunto(s)
Bromelaínas/química , Fenilalanina/química , Polietilenglicoles/química , Tensoactivos/química , Temperatura , Bromelaínas/farmacología , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Emulsiones/química , Humanos , Tamaño de la Partícula , Fenilalanina/farmacología , Polietilenglicoles/farmacología , Propiedades de Superficie , Tensoactivos/farmacología
20.
Int J Biol Macromol ; 124: 377-388, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30465844

RESUMEN

Fucosylated chondroitin sulfate from Isostichopus badionotus (fCS-Ib) is a kind of sulfated polysaccharides with well-repeated structure. In our former publications, fCS-Ib has been reported to be a functional food ingredient with hypoglycemic and antilipemic activities. However, there is no systematic study to investigate the effects of fCS-Ib on metabolic syndromes. In the present study, C57BL/6 mice fed on a high-fat and high sucrose diet (HFSD) for 6 weeks was used to cause metabolic syndromes. The final results showed that fCS-Ib alleviated obesity, hyperlipidemia, hyperglycemia, inflammation, liver steatosis, and adipocyte hypertrophy caused by HFSD. Meanwhile, fCS-Ib showed powerful effects on moderating gut microbiota dysbiosis in the HFSD-fed mice. Supplement of fCS-Ib could reduce ratio of Firmicutes to Bacteroidetes by decreasing abundance of Lachnospiraceae and Allobaculum while increasing abundance of Porphyromonadaceae, Barnesiella, and Bacteroides. Our results showed that fCS-Ib could be further developed as a potential pharmaceutical agent to prevent metabolic syndromes and gut microbiota dysbiosis.


Asunto(s)
Sulfatos de Condroitina/administración & dosificación , Disbiosis/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Pepinos de Mar/química , Adipocitos/efectos de los fármacos , Adipocitos/patología , Animales , Sulfatos de Condroitina/química , Sulfatos de Condroitina/aislamiento & purificación , Dieta Alta en Grasa/efectos adversos , Disbiosis/inducido químicamente , Disbiosis/microbiología , Hígado Graso/inducido químicamente , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Fructosa/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Hiperglucemia/inducido químicamente , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/patología , Hiperlipidemias/inducido químicamente , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/patología , Hipertrofia/inducido químicamente , Hipertrofia/tratamiento farmacológico , Hipertrofia/patología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/patología , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/patología , Ratones , Obesidad/inducido químicamente , Obesidad/tratamiento farmacológico , Obesidad/patología
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