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1.
Carbohydr Polym ; 302: 120329, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36604040

RESUMO

Starch from Pueraria lobata (PLS) had polyhedral or spherical granules, displaying a bimodal size distribution within 0.6-30 µm. It showed a trimodal distribution of different molecular weight peaks, with amylose fraction of 18.2 %. PLS had a high crystallinity degree of 37.76 % and consisted of C-type starch, which gelatinized at 64.46-79.61 °C, with a high range of gelatinization (15.15 °C) and high enthalpy (13.98 J/g). A 21-day supplementation of PLS presented a regulative effect on gut microbiota in normal mice, and alleviated DSS-induced murine colitis through attenuating colonic inflammation, maintaining barrier function, preventing gut dysbiosis, increasing the short-chain fatty acids production and inhibiting NF-κB/IL-1ß axis. The protective effect of PLS against colitis was in a gut microbiota-dependent manner. Notably, the amylose fraction was responsible for the prebiotic effect of PLS. The results would potentiate new application of PLS and the amylose fraction as functional prebiotics for prevention of colitis.


Assuntos
Colite , Pueraria , Camundongos , Animais , Amilose , Dextranos , Amido , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
2.
Artif Cells Nanomed Biotechnol ; 51(1): 33-40, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36656591

RESUMO

Sepsis is a devastating complication of infection and injury that, through widespread endothelial dysfunction, can cause perfusion deficits and multi-organ failure. To address the recognised need for therapeutics targetting the endothelial barrier, a topical formulation (CUR; VASCEPTOR™; Vascarta Inc, Summit, NJ) was developed to transdermally deliver bio-active concentrations of curcumin-an anti-inflammatory and nitric oxide promoter. Male, Sprague Dawley rats were treated daily with lipopolysaccharide (LPS, 10 mg/kg, IP) to induce endotoxemia, and topical applications of Vehicle Control (LPS + VC; N = 7) or Curcumin (LPS + CUR; N = 7). A third group received neither LPS nor treatment (No-LPS; N = 8). After 72 h, animals were surgically prepared for measurements of physiology and endothelial dysfunction in the exteriorised spinotrapezius muscle through the extravasation of 67 kDa TRITC-BSA (albumin) and 500 kDa FITC-dextran (dextran). At 72 h, LPS + VC saw weight loss, and increases to pulse pressure, lactate, pCO2, CXCL5 (vs No-LPS) and IL-6 (vs 0 h; p < 0.05). LPS + CUR was similar to No-LPS, but with hypotension. Phenylephrine response was increased in LPS + CUR. Regarding endothelial function, LPS + CUR albumin and dextran extravasation were significantly reduced versus LPS + VC suggesting that Curcumin mitigated endotoxemic endothelial dysfunction. The speculated mechanisms are nitric oxide modulation of the endothelium and/or an indirect anti-inflammatory effect.


Assuntos
Curcumina , Endotoxemia , Animais , Masculino , Ratos , Albuminas , Anti-Inflamatórios , Curcumina/farmacologia , Dextranos , Endotélio , Endotoxemia/induzido quimicamente , Endotoxemia/tratamento farmacológico , Lipopolissacarídeos , Óxido Nítrico , Ratos Sprague-Dawley
3.
AAPS J ; 25(1): 22, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36720729

RESUMO

Influenza is a global health concern with millions of infections occurring yearly. Seasonal flu vaccines are one way to combat this virus; however, they are poorly protective against influenza as the virus is constantly mutating, particularly at the immunodominant hemagglutinin (HA) head group. A more broadly acting approach involves Computationally Optimized Broadly Reactive Antigen (COBRA). COBRA HA generates a broad immune response that is capable of protecting against mutating strains. Unfortunately, protein-based vaccines are often weekly immunogenic, so to help boost the immune response, we employed the use of acetalated dextran (Ace-DEX) microparticles (MPs) two ways: one to conjugate COBRA HA to the surface and a second to encapsulate cGAMP. To conjugate the COBRA HA to the surface of the Ace-DEX MPs, a poly(L-lactide)-polyethylene glycol co-polymer with a vinyl sulfone terminal group (PLLA-PEG-VS) was used. MPs encapsulating the STING agonist cGAMP were co-delivered with the antigen to form a broadly active influenza vaccine. This vaccine approach was evaluated in vivo with a prime-boost-boost vaccination schedule and illustrated generation of a humoral and cellular response that could protect against a lethal challenge of A/California/07/2009 in BALB/c mice.


Assuntos
Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Humanos , Camundongos , Dextranos , Influenza Humana/prevenção & controle , Sulfonas , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle , Vacinas de Subunidades
4.
Anal Chim Acta ; 1243: 340815, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36697184

RESUMO

Acetylcholinesterase (AChE) is regarded as a biomarker of Alzheimer's disease (AD), and its inhibitors show great potential in AD therapy as AChE can increase the neurotoxicity of the amyloid component that induces AD. Because of this, it is crucial and significant to develop a simple and highly sensitive strategy to monitor AChE levels and screen highly efficient AChE inhibitors. Herein, we synthesize an ultrathin two-dimensional (2D) metal-organic framework (MOF) based on copper-catecholate (Cu-CAT) via dextran assisted ultrasound exfoliation, followed by construction of a sensitive sensor for the monitoring AChE and screening of its inhibitors. By adding AChE, the acetylthiocholine (ATCh) substrate is hydrolyzed to be thiocholine (TCh), which decreases the peroxidase-like activity of Cu-CAT nanosheets (Cu-CAT NSs), impairing the signal reaction of 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized-TMB (ox-TMB). In the presence of an AChE inhibitor, the signal can be gradually restored. The newly developed sensor shows high sensitivity and selectivity for AChE and huperzine A (HA, an effective drug for AD, an acetylcholine receptor antagonist), as well as for AD drug discovery from traditional Chinese herbs. The limit of detection of the sensor for AChE is 0.01 mU mL-1 and the average IC50 value of HA is 30.81 nM under the optimal of catalysis conditions. Compared with the 3D bulk Cu-CAT, the current 2D Cu-CAT NSs exhibit higher peroxidase activity due to more catalytic active site exposure. This study provides a strategy to prepare an ultrathin 2D MOF with high catalytic activity and new insights for the construction of a biosensor to monitor AChE and new AD drugs.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Acetilcolinesterase , Dextranos , Ultrassom , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Peroxidases , Técnicas Biossensoriais/métodos
5.
Food Funct ; 14(2): 720-733, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36598450

RESUMO

As potential candidates for treating ulcerative colitis (UC), polysaccharides have been attracting extensive interest in recent years. Cordyceps sinensis (C. sinensis) is a kind of traditional Chinese edible food, and its polysaccharide fractions have been found to be effective in regulating immunity and protecting the kidneys. To determine the potential function of polysaccharides from natural C. sinensis on UC, their effects in terms of histological, serological, biochemical, and immunological aspects on dextran sulphate sodium (DSS)-induced colitis mice model were investigated. Results showed that the polysaccharides significantly alleviated colitis by increasing the colon length, alleviating colon tissue damage, and inhibiting the activation of the NF-κB pathway. In addition, polysaccharides reduced the contents of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the serum, increased the number of goblet cells, and improved the expression of intestinal tight junction proteins (Occludin and Claudin-1). They also evidently enhanced the formation of IgA-secretory cells and sIgA contents. Furthermore, the polysaccharides modulated the gut microbiota by decreasing the relative abundance of Bilophila and increasing the relative abundance of Dehalobacterium, Coprococcus, Oscillospira, and Desulfovibrio, which is accompanied by an increase in the short chain fatty acids' (SCFAs) concentrations in cecal contents. These results suggested that C. sinensis polysaccharides possessed promising intervening effects on experimental acute UC in mice.


Assuntos
Colite Ulcerativa , Colite , Cordyceps , Animais , Camundongos , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colo/metabolismo , Cordyceps/metabolismo , Sulfato de Dextrana/toxicidade , Dextranos/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo
6.
J Agric Food Chem ; 71(3): 1577-1592, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36634244

RESUMO

Ulcerative colitis (UC) is associated with brain neurotransmitter disorders and intestinal dysbiosis. Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin, which has a wide range of biological activities. However, the effects of surfactin on DSS-induced colitis have not been reported. In the present study, oral surfactin significantly ameliorated colitis in a mouse model and reduced depression-like behavior, such as slowed walking speed, shortened movement distance in the open field test, and weakened exploration ability in the light-dark shuttle test. Surfactin noticeably improved gut microbial dysbiosis, intestinal barrier dysfunction in the colon, and blood-brain barrier dysfunction in the brain. Furthermore, the colon levels of occludin were upregulated by 68.51%, and the brain levels of occludin and ZO-1 were upregulated by 77.81% and 36.42%, respectively. Surfactin supplementation also inhibited inflammatory responses by inactivating the tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), and NLRP3 signaling pathways in the colon and brain. Thus, we believe that surfactin improved the behavioral disorders by upregulating the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF), suppressing the inflammatory responses, and improving the blood-brain barrier dysfunction. Surfactin also reduced the abundances of gut microbes that are related to colitis, especially targeting facultative anaerobes of the phylum Proteobacteria, and it increased the abundance of beneficial bacteria such as Lactobacillus and unidentified Prevotella. Combined with its nontoxic nature observed in this long-term study in mice, oral surfactin might be a promising intervention strategy for preventing colitis by acting on the microbiota-gut-brain axis.


Assuntos
Encefalopatias , Besouros , Colite Ulcerativa , Colite , Animais , Camundongos , Encéfalo , Eixo Encéfalo-Intestino , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Sulfato de Dextrana/toxicidade , Dextranos , Modelos Animais de Doenças , Disbiose , Camundongos Endogâmicos C57BL , Ocludina
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(1): 57-62, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36631016

RESUMO

Objective To investigate the possible off-target effects of dynamin (DNM) inhibitor Dyngo-4a in dynamin-dependent endocytic pathways. Methods Bone marrow mesenchymal stem cells (BMSCs) obtained from SD rats were isolated and cultured, and identified by flow cytometry. The cells were divided into inhibitor control group, Dyngo-4a-treated group, negative control siRNA (si-NC) transfection group, DNM2 siRNA transfection (si-DNM2) group, si-DNM2 and Dyngo-4a co-treated group. Real time quantitative PCR and Western blot analysis were used to verify the silencing efficiencies of DNM2 gene and CCK-8 assay were used to detect the cell viability after Dyngo-4a treatment. Confocal microscopy was used to detect the number and mean fluorescence intensity (MFI) of transferrin-Dylight649-positive and dextran-TMR-positive vesicles. Results The mRNA and protein expression levels of DNM2 were down-regulated using small interfering RNA. The number of transferrin-Dylight649-positive vesicles significantly decreased in si-DNM2 group compared with si-NC group. For the number and MFI of dextran-TMR-positive vesicles, no significant change was observed between the si-DNM2 group and the si-NC group, but there was a significant reduction in the si-DNM2 and Dyngo-4a co-treated group compared with the si-DNM2 group. A significant decrease was also found in the Dyngo-4a-treated group compared with the inhibitor control group. Conclusion The off-target effects of dynamin inhibitor Dyngo-4a presents in the internalization of dextran by BMSCs.


Assuntos
Dextranos , Células-Tronco Mesenquimais , Ratos , Animais , Dextranos/metabolismo , Ratos Sprague-Dawley , Dinaminas/genética , Células-Tronco Mesenquimais/metabolismo , RNA Interferente Pequeno/genética , Transferrinas , Células da Medula Óssea/metabolismo
8.
J Agric Food Chem ; 71(2): 1100-1112, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36604158

RESUMO

Glucoraphanin, rich in broccoli seed extract (BSE), is generally inert but can be biotransformed into active sulforaphane by gut bacteria. This study aimed to screen probiotics with glucoraphanin-metabolizing ability and explore the effect of a combination of strain and BSE on colitis induced by dextran sulfate sodium (DSS) in mice. Bifidobacterium longum CCFM1206 was isolated from healthy adult feces. Ultra-high-performance liquid chromatography Q Exactive mass spectrometry analysis revealed the presence of sulforaphane, sulforaphane-l-cysteine, and erucin in the BSE supernatant fermented by B. longum CCFM1206 in vitro. Combined and individual interventions of BSE and B. longum CCFM1206 were applied to explore the effects on DSS-induced colitis. The results suggested that the combination of B. longum CCFM1206 and BSE could ameliorate colitis symptoms, relieve colonic inflammatory reactions and oxidative stress, and protect the intestinal barrier in DSS-induced mice. In comparison to the BSE intervention alone, the combined intervention of B. longum CCFM1206 and BSE promoted the generation of sulforaphane and sulforaphane-N-acetylcysteine in mice colon from 220.88 ± 19.81 to 333.99 ± 36.46 nmol/g and from 232.04 ± 26.48 to 297.50 ± 40.08 nmol/g dry weight feces, respectively. According to quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis, B. longum CCFM1206 and BSE effectively activated the transcription and expression of genes related to the Nrf2 signaling pathway. These results were intended to elucidate that probiotics could elevate the bioactivity of dietary phytochemicals in vivo, and the combination had potential for therapeutic treatment of colitis.


Assuntos
Bifidobacterium longum , Colite , Camundongos , Animais , Bifidobacterium longum/metabolismo , Dextranos/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Colo/metabolismo , Biotransformação , Sulfatos/metabolismo , Sódio/metabolismo , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
9.
BMC Microbiol ; 23(1): 9, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627557

RESUMO

Cytosine deaminase (CDA) is a prodrug mediating enzyme converting 5-flurocytosine into 5-flurouracil with profound broad-range anticancer activity towards various cell lines. Availability, molecular stability, and catalytic efficiency are the main limiting factors halting the clinical applications of this enzyme on prodrug and gene therapies, thus, screening for CDA with unique biochemical and catalytic properties was the objective. Thermotolerant/ thermophilic fungi could be a distinctive repertoire for enzymes with affordable stability and catalytic efficiency. Among the recovered thermotolerant isolates, Aspergillus niger with optimal growth at 45 °C had the highest CDA productivity. The enzyme was purified, with purification 15.4 folds, molecular mass 48 kDa and 98 kDa, under denaturing and native PAGE, respectively. The purified CDA was covalently conjugated with dextran with the highest immobilization yield of 75%. The free and CDA-dextran conjugates have the same optimum pH 7.4, reaction temperature 37 °C, and pI 4.5, and similar response to the inhibitors and amino acids suicide analogues, ensuring the lack of effect of dextran conjugation on the CDA conformational structure. CDA-Dextran conjugates had more resistance to proteolysis in response to proteinase K and trypsin by 2.9 and 1.5 folds, respectively. CDA-Dextran conjugates displayed a dramatic structural and thermal stability than the free enzyme, authenticating the acquired structural and catalytic stability upon dextran conjugation. The thermal stability of CDA was increased by about 1.5 folds, upon dextran conjugation, as revealed from the half-life time (T1/2). The affinity of CDA-conjugates (Km 0.15 mM) and free CDA (Km 0.22 mM) to deaminate 5-fluorocytosine was increased by 1.5 folds. Upon dextran conjugation, the antiproliferative activity of the CDA towards the different cell lines "MDA-MB, HepG-2, and PC-3" was significantly increased by mediating the prodrug 5-FC. The CDA-dextran conjugates strongly reduce the tumor size and weight of the Ehrlich cells (EAC), dramatically increase the titers of Caspase-independent apoptotic markers PARP-1 and AIF, with no cellular cytotoxic activity, as revealed from the hematological and biochemical parameters.


Assuntos
Citosina Desaminase , Pró-Fármacos , Humanos , Aspergillus niger , Citosina Desaminase/metabolismo , Dextranos/metabolismo , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Cinética , Peptídeo Hidrolases/metabolismo , Pró-Fármacos/farmacologia , Proteólise , Linhagem Celular Tumoral
10.
Mol Pharm ; 20(1): 303-313, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36484773

RESUMO

We have been investigating the potential of cell-penetrating peptides anchored to polymeric platforms as a novel absorption enhancer which delivers biologics into systemic circulation via mucosal routes. Our previous mouse experiments demonstrated that hyaluronic acid modified with l-octaarginine, a typical cell-penetrating peptide, via a tetraglycine spacer significantly enhanced the mucosal absorption of protein drugs applied into the nasal cavities, irrespective of the molecular weights (Mw) of the drugs. The present study evaluated the performance of tetraglycine-l-octaarginine-linked hyaluronic acid applied via various mucosal routes. Somatropin (Mw: ca. 22.1 kDa) was moderately absorbed from the lung mucosa, and the mean absolute bioavailability (BA) reached 19% under enhancer-free conditions; nevertheless, its BA under intranasal administration was approximately 1% or less. Its BA significantly elevated to 46% on average through intrapulmonary coadministration with tetraglycine-l-octaarginine-linked hyaluronic acid. When the administration site was replaced with the oral cavities, an extreme reduction in somatropin absorption was observed with a mean BA of 0.056% under enhancer-free conditions. Intraoral coadministration with tetraglycine-l-octaarginine-linked hyaluronic acid resulted in a 6.3-fold elevation of somatropin absorption with statistical significance. A similar enhancement was observed under intrarectal administration with a further reduction in BA. On the other hand, the hyaluronic acid derivative did not exhibit the absorption-enhancing ability under intragastric administration, probably due to the lack of stabilization effects against enzyme-susceptible biologics. The results indicated that the intrapulmonary route was suitable for maximizing the mucosal absorption of biologics, and that there was a likelihood of the intraoral route with user convenience. When somatropin was substituted with fluorescein isothiocyanate-conjugated dextran with an average Mw range of 4-70 kDa, similar phenomena were observed under intrapulmonary and intranasal administration. BA decreased with an increase in the Mw of dextran; however, the ratio of BA under enhancer-present conditions to that under enhancer-free conditions was consistently around 3, indicating that the performance of the hyaluronic acid derivative was Mw-independent, irrespective of the administration route.


Assuntos
Peptídeos Penetradores de Células , Hormônio do Crescimento Humano , Camundongos , Animais , Peptídeos Penetradores de Células/química , Mucosa Nasal/metabolismo , Dextranos/farmacologia , Ácido Hialurônico/metabolismo , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/farmacologia , Administração Intranasal
11.
Methods Mol Biol ; 2592: 163-174, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36507992

RESUMO

Pancreatic islet transplantation (Tx) has a lifesaving potential for type 1 diabetes (T1D) patients. Islet damage during and after transplantation is one of the major reasons hampering its wide clinical application. Inability to monitor transplanted islets also severely limits our understanding of mechanisms regarding declining graft function after transplantation. Our team has proposed to use magnetic nanoparticles conjugated to siRNA (MN-siRNA) to label islets prior to transplantation with two goals in mind: to protect them from damage by silencing harmful genes and to monitor them after transplantation using noninvasive magnetic resonance imaging (MRI). This manuscript provides a step-by-step protocol for the synthesis and characterization of MN-siRNA probes.


Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Humanos , Dextranos , RNA Interferente Pequeno/genética , Transplante das Ilhotas Pancreáticas/métodos , Imageamento por Ressonância Magnética/métodos , Nanopartículas Magnéticas de Óxido de Ferro
12.
Drug Deliv Transl Res ; 13(1): 308-319, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35851672

RESUMO

In the design of injectable antimicrobial dextran-alginate hydrogels, the impact of dextran oxidation and its subsequent changes in molecular weight and the incorporation of glycol chitosan on (i) gel mechanical strength and (ii) the inhibitory profile of an encapsulated bacteriocin, nisin A, are explored. As the degree of oxidation increases, the weight average molecular mass of the dextran decreases, resulting in a reduction in elastic modulus of the gels made. Upon encapsulation of the bacteriocin nisin into the gels, varying the dextran mass/oxidation level allowed the antimicrobial activity against S. aureus to be controlled. Gels made with a higher molecular weight (less oxidised) dextran show a higher initial degree of inhibition while those made with a lower molecular weight (more oxidised) dextran exhibit a more sustained inhibition. Incorporating glycol chitosan into gels composed of dextran with higher masses significantly increased their storage modulus and the gels' initial degree of inhibition.


Assuntos
Anti-Infecciosos , Bacteriocinas , Hidrogéis , Dextranos , Staphylococcus aureus
13.
Int J Mol Med ; 51(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36484371

RESUMO

Disruption of iron homeostasis is associated with multiple diseases. It has been found that patients with genetic iron overload develop massive iron deposition in the pancreas. However, few studies have focused on the effect of secondary iron overload on the pancreas. The objective of the present study was to investigate the pathogenic consequences of secondary iron overload in mice. An iron overload mouse model was constructed by intraperitoneal injection of 120 mg/kg body weight of iron dextran every other week for 12 weeks. Iron deposition, immunocyte infiltration, fibrosis, oxidative stress and ferroptosis were assessed using Prussian blue staining, immunohistochemical analysis, Masson staining, Sirius red staining, RT­qPCR analysis and western blot analysis. It was found that iron­overloaded mice showed pancreatic iron overload, together with elevated gene expression of the iron storage factor ferritin H, and decreased expression of the iron transportation mediator divalent metal transporter 1, ferroportin 1 and transferrin receptor. Iron­overloaded mice developed mild pancreatitis with increased serum amylase and lipase activities, as well as elevated gene expression levels of pro­inflammatory cytokines, including interleukin (IL)­1ß, IL­6 and inducible nitric oxide synthase. Acinar atrophy, massive immunocyte infiltration and pancreatic fibrosis were noted in the iron­overloaded mice. As an underlying mechanism, iron­overloaded mice showed increased pancreatic oxidative stress, with an elevated malondialdehyde level, and decreased SOD and glutathione peroxidase activity. Furthermore, iron overload led to ferroptosis with promoted expression of cytochrome c oxidase subunit II, and decreased transcripts of glutathione peroxidase 4 and solute carrier family 7 member 11. These results provided evidence that multiple intraperitoneal injections of iron dextran in mice lead to iron overload­induced chronic pancreatitis, which suggested that secondary iron overload is a risk factor for pancreatitis and highlights the importance of iron in maintaining the normal functions of the pancreas.


Assuntos
Sobrecarga de Ferro , Pancreatite Crônica , Camundongos , Animais , Células Acinares , Dextranos , Sobrecarga de Ferro/complicações , Ferro
14.
Biomacromolecules ; 24(1): 367-376, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36479984

RESUMO

Here, we describe the all-aqueous bicontinuous emulsions with cholesteric liquid crystal domains through hierarchical colloidal self-assembly of nanoparticles. This is achieved by homogenization of a rod-like cellulose nanocrystal (CNC) with two immiscible, phase separating polyethylene glycol (PEG) and dextran polymer solutions. The dispersed CNCs exhibit unequal affinity for the binary polymer mixtures that depends on the balance of osmotic and chemical potential between the two phases. Once at the critical concentration, CNC particles are constrained within one component of the polymer phases and self-assemble into a cholesteric organization. The obtained liquid crystal emulsion demonstrates a confined three-dimensional percolating bicontinuous network with cholesteric self-assembly of CNC within the PEG phase; meanwhile, the nanoparticles in the dextran phase remain isotropic instead. Our results provide an alternative way to arrest bicontinuous structures through intraphase trapping and assembling of nanoparticles, which is a viable and flexible route to extend for a wide range of colloidal systems.


Assuntos
Cristais Líquidos , Nanopartículas , Celulose/química , Emulsões/química , Cristais Líquidos/química , Dextranos , Polímeros/química , Nanopartículas/química , Polietilenoglicóis , Água/química
15.
Biomacromolecules ; 24(1): 283-293, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36511362

RESUMO

The membrane-less organelles (MLOs) with subcompartments are formed via liquid-liquid phase separation (LLPS) in the crowded cell interior whose background molecules are up to 400 mg/mL. It is still a puzzle how the background molecules regulate the formation, dynamics, and functions of MLOs. Using biphasic coacervate droplets formed by poly(l-lysine) (PLL), quaternized dextran (Q-dextran), and single-stranded oligonucleotides (ss-oligo) as a model of MLO, we online monitored the LLPS process in Bovine Serine Albumin (BSA) solution up to 200.0 mg/mL. Negatively charged BSA is able to form complex or coacervate with positively charged PLL and Q-dextran and thus participates in the LLPS via nonspecific interactions. Results show that BSA effectively regulates the LLPS by controlling the phase distribution, morphologies, and kinetics. With increasing BSA concentration, the spherical biphasic droplets evolve in sequence into phase-inverted flower-like structure, worm-like chains, network structures, and confined coacervates. Each kind of morphology is formed via its own specific growth and fusion pathway. Our work suggests that MLOs could be controlled solely by the crowded environment and provides a further step toward understanding the life process in cell.


Assuntos
Biopolímeros , Dextranos , Lisina , Organelas , Soroalbumina Bovina/química , Biopolímeros/química
16.
Food Funct ; 14(2): 857-873, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36537246

RESUMO

Poria cocos, a widely accepted function food in China, has multiple pharmacological activities. This study aimed to investigate the therapeutic effect and molecular mechanism of Poria cocos oligosaccharides (PCOs) against dextran sodium sulfate (DSS)-induced mouse colitis. In this study, BALB/c mice were treated with 3% (w/v) DSS for seven days to establish a colitis model. The results showed that oral administration of PCOs (200 mg per kg per day) significantly reversed the changes in the physiological indices in colitis mice, including body weight, disease activity index scores (DAI), spleen index, and colon length. From the qRT-PCR assay, it was observed that PCOs suppressed the mRNA expression of pro-inflammatory cytokines, such as Tnf-α, Il-1ß, and Il-6. In addition, PCOs protected the intestinal barrier from damage by promoting the expression of mucins and tight junction proteins at both mRNA and protein levels. Upon 16S rDNA sequencing, it was observed that PCO treatment partly reversed the changes in the gut microbiota of colitis mice by selectively regulating the abundance of specific bacteria. And Odoribacter, Muribaculum, Desulfovibrio, Oscillibacter, Escherichia-Shigella, and Turicibacter might be the critical bacteria in improving colitis via PCOs. Finally, using antibiotic mixtures to destroy the intestinal bacteria, we documented that PCO fermentation broth (PCO FB) instead of PCOs prevented the occurrence of colitis in gut microbiota-depleted mice. In conclusion, PCOs showed a protective effect on colitis by reversing gut microbiota dysbiosis. Our study sheds light on the potential application of PCOs as a prebiotic for treating colitis.


Assuntos
Colite , Microbioma Gastrointestinal , Wolfiporia , Animais , Camundongos , Colite/induzido quimicamente , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana , Dextranos , Modelos Animais de Doenças , Disbiose , Camundongos Endogâmicos C57BL , RNA Mensageiro
17.
ACS Appl Bio Mater ; 6(1): 146-156, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36503228

RESUMO

Magnetic nanoparticles are an attractive bioseparation tool due to their magnetic susceptibility and high adsorption capacity for different types of molecules. A major challenge for separation is to generate selectivity for a target molecule, or for a group of molecules in complex environments such as cell lysates. It is crucial to understand the factors that determine the targets' adsorption behavior in mixtures for triggering intended interactions and selectivity. Here we use a model system containing three molecules, each of them a common representative of the more abundant types of macromolecules in living systems: sodium oleate (SO), a fatty acid; bovine serum albumin (BSA), a protein; and dextran, a polysaccharide. Our results show that (a) the BSA adsorption capacity on the iron oxide material depends markedly on the pH, with the maximum capacity at the pI of the protein (0.39 g gMNP-1 ); (b) sodium oleate, a strongly negatively charged molecule, an organic anion, renders a maximum adsorption capacity of 0.40 g gMNP-1, even at pHs at which oleate as well as the nanoparticle surface are negatively charged; (c) the adsorbed masses of dextran, a neutral sugar, are lower than for the other two molecules, between 0.09 and 0.13 g gMNP-1, regardless of the system's pH. We observe an unexpected behavior in mixtures: SO completely prevents the adsorption of BSA, and dextran decreases the adsorption of the other competitors, SO and BSA, while adsorbing at the same capacities, unaffected by either the presence of the other two molecules or the pH. BSA does not decrease the oleate adsorption capacity. We demonstrate the essential role of pH in the adsorption of BSA (a protein) and SO (a fatty acid), as well as its impact in the structural organization of the oleate molecules in water. Moreover, we present exciting data on the adsorption of the molecules in competition, revealing the need to focus on interaction studies in more complex environments. This study attempts to open the scope of the current research of bio-nano interactions to not only proteins but also to mixtures, and generally to molecules with other physicochemical characteristics. Furthermore, we contribute to the understanding of multicomponent systems with the vision set in enhancing biomass exploitation and biofractionation processes.


Assuntos
Nanopartículas de Magnetita , Ácido Oleico , Ácido Oleico/química , Ácidos Graxos , Dextranos , Soroalbumina Bovina/química
18.
Fish Shellfish Immunol ; 132: 108498, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36539168

RESUMO

White shrimp (Penaeus vannamei) is an important culture species in Taiwan but often encounters disease infection by Vibrio parahaemolyticus that cause acute hepatopancreatic necrosis disease (AHPND). This study investigates the effects of dietary supplementation of Leuconostoc mesenteroide B4 and its fermentate (dextran) on the immune response, intestinal morphology, disease resistance, and immune-related gene expression in white shrimp. In comparison to the control group, the shrimp fed with a diet containing B4+dextran (107 CFU B4/g feed and 0.05% dextran) for 14, 28, 42 and 56 days had a significantly higher feed efficiency, weight gain and specific growth rate. A significantly higher villus height in the intestine and higher survival rate after challenging with V. parahaemolyticus was recorded for the B4+dextran group. Flow cytometry analysis demonstrated that the group that had ingested B4+dextran had a higher total hemocyte count and a higher proportion of semi-granulocytes, but a lower percentage of granulocytes compared to the control group. The shotgun metagenomic results in the midgut revealed that Leuco. mesenteroides was barely found in the midgut of the shrimp, suggesting that this microbe and its transient presence in the midgut is not the direct mechanism underlying the improved shrimp growth in the treated sample. Instead, dextran, a key ingredient in the B4 fermentate, on the dynamic of the microbial populations in shrimp, possibly promoting the diversity of gut microbes, especially the beneficial microbes, and thereby rendering protection against AHPND. In terms of comparing the gene expression between the control and synbiotic groups, pre- and post-bacterial challenge, a higher expression level of immune genes was mostly found in the B4+dextran group after challenging it with V. parahaemolyticus (group B4+dextran-VP) in the hepatopancreas and hemocyte. In contrast, the transcript level of immune-related genes was found to be higher in the B4+dextran group than other combinations in the midgut. Taken together, this study found that dietary addition of synbiotic Leuco. mesenteroides B4 and dextran can improve the growth performance, intestinal morphology and microbiome, regulation of immune genes and disease resistance against V. parahaemolyticus infection in white shrimp.


Assuntos
Leuconostoc mesenteroides , Penaeidae , Simbióticos , Vibrio parahaemolyticus , Animais , Resistência à Doença , Vibrio parahaemolyticus/fisiologia , Dextranos/farmacologia , Imunidade Inata/genética
19.
Food Chem ; 408: 135190, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36535187

RESUMO

Calcium has limited bioavailability because of the formation of calcium phosphate deposits in the gastrointestinal tract. In this study, we prepared a dextran-casein phosphopeptide (CPP)-Ca2+ delivery system and evaluated for Ca2+ binding mechanism, structure, stability, and sustained release of Ca2+ and assessed inhibition of calcium phosphate precipitation. The results revealed that Ca2+ binds to dextran-CPP through the phosphate, carboxyl, and amino groups and forms crystal clusters. Furthermore, compared with single polymer CPP-Ca2+ conjugates, copolymer dextran-CPP-Ca2+ conjugates exhibited improved stability at various conditions (pH, temperature, and coexisting food), efficiently reduced the calcium phosphate precipitation, and improved sustained-release of Ca2+. Collectively, dextran-CPP-Ca2+ conjugates can be an efficient Ca2+ delivery system.


Assuntos
Cálcio , Dextranos , Cálcio/química , Caseínas/química , Fosfatos de Cálcio , Fosfopeptídeos/química
20.
Int J Biol Macromol ; 228: 794-807, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36535351

RESUMO

This review extensively surveys the biomedical applications of hydrogels containing dextran. Dextran has gained much attention as a biomaterial due to its distinctive properties such as biocompatibility, non-toxicity, water solubility and biodegradability. It has emerged as a critical constituent of hydrogels for biomedical applications including drug delivery devices, tissue engineering scaffolds and biosensor materials. The benefits, challenges and potential prospects of dextran-based hydrogels as biomaterials are highlighted in this review.


Assuntos
Dextranos , Hidrogéis , Materiais Biocompatíveis , Tecidos Suporte , Engenharia Tecidual
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