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1.
Food Funct ; 15(14): 7553-7566, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38932628

RESUMO

We previously confirmed that tannic acid could delay the metabolism of resistant starch in vitro, which suggested that tannic acid might deliver resistant starch to the distal colon in vivo. Accordingly, co-supplementation of resistant starch and tannic acid might be beneficial for keeping the distal colon healthy. Thus, this study compared the effects of resistant starch, tannic acid and their mixtures on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. It was found that the mixtures had a more profound effect on ameliorating DSS-induced ulcerative colitis than resistant starch or tannic acid. In particular, the mixtures reversed the histology damage of the distal colon induced by DSS, while resistant starch or tannic acid alone did not. The mixtures also had a stronger ability to resist oxidative stress and inhibit inflammation in the distal colon. These results suggested that resistant starch and tannic acid synergistically alleviated DSS-induced ulcerative colitis, particularly in the distal colon. On the other hand, DSS decreased the production of short-chain fatty acids and induced significant microbial disorder, while the administration of resistant starch, tannic acid and their mixtures reversed the above shifts caused by DSS. In particular, the mixtures exhibited stronger prebiotic activity, as indicated by the microbial composition and production of short-chain fatty acids. Therefore, it was inferred that tannic acid delivered resistant starch to the distal colon of mice, and thus the mixtures had stronger prebiotic activity. As a result, the mixtures effectively alleviated ulcerative colitis in the whole colon.


Assuntos
Colite Ulcerativa , Colo , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Taninos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Animais , Taninos/farmacologia , Sulfato de Dextrana/efeitos adversos , Camundongos , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Masculino , Amido/farmacologia , Modelos Animais de Doenças , Amido Resistente/farmacologia , Sinergismo Farmacológico , Ácidos Graxos Voláteis/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polifenóis
2.
Food Chem ; 452: 139473, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38723564

RESUMO

We had previously observed that adding pectin into milk before fermentation inhibited gelation of yogurt but did not affect the pH. Thus, this work aimed to prepare such liquid yogurt and clarify its formation mechanism. It was found that liquid yogurt was obtained in the presence of 0.10%-0.20% pectin. However, at lower or higher pectin concentrations, yogurt was gelled. Confocal laser scanning microscopy analysis demonstrated that 0.10%-0.20% pectin induced milk protein aggregating into separated particles rather than a continuous network, which explained why liquid yogurt was formed. Moreover, adding 0.10%-0.20% pectin into the casein micelle suspension induced aggregation of casein micelles at pH 6.8. After pH decreased to 4.3, casein micelles showed more aggregation but they were still separated particles, which was the same in the corresponding yogurt samples. These results suggested that pectin changed the aggregation mode of casein micelles and induced formation of liquid yogurt.


Assuntos
Pectinas , Iogurte , Iogurte/análise , Pectinas/química , Concentração de Íons de Hidrogênio , Leite/química , Animais , Micelas , Caseínas/química , Fermentação , Proteínas do Leite/química , Manipulação de Alimentos
3.
Food Res Int ; 176: 113844, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163734

RESUMO

Rice protein hydrolysate (RPH) and feruloyl oligosaccharides (FOs) were conjugated under the catalysis of laccase and free radical, and the structure and properties of the resultant conjugates were studied. Electrophoresis analysis demonstrated that conjugation with FOs increased the molecular weight of some fractions in RPH, which confirmed the formation of both conjugates. The conjugation degree of laccase-induced conjugate and radical-induced conjugate was 60.45% and 22.70%, respectively. Laccase-catalyzed conjugation decreased the tyrosine residue content of RPH but had no significant effect on the free amino group content, which suggested that tyrosine residues were the conjugation site in the laccase-induced conjugate. However, radical-catalyzed conjugation decreased both the free amino group content and the tyrosine residue content, which indicated that both free amino groups and tyrosine residues were the conjugation site in the radical-induced conjugate. The ultraviolet, fluorescence and circular dichroism spectroscopy analysis revealed that conjugation with FOs significantly altered the secondary and tertiary structure of RPH. In addition, conjugation with FOs increased the solubility and antioxidant activity of RPH but decreased the emulsifying activity and stability. Particularly, the radical-induced conjugate had greater anti-aggregation capacity and antioxidant activity but lower emulsifying activity and stability than the laccase-induced conjugate, which might be due to that their conjugation site and degree were different.


Assuntos
Lacase , Oryza , Lacase/química , Antioxidantes/química , Hidrolisados de Proteína , Oligossacarídeos/química , Tirosina
4.
Food Chem ; 440: 138261, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150905

RESUMO

This work investigated the effect of tannic acid on the fermentation rate of resistant starch. It was found that 1.0 and 1.5 µmol/L tannic acid decreased the rate of producing gas and short-chain fatty acids (SCFAs) from fermentation of resistant starch, and 1.5 µmol/mL tannic acid had a more profound effect, which confirmed that tannic acid delayed the metabolism of resistant starch. Moreover, tannic acid significantly inhibited the α-amylase activity during fermentation. On the other hand, tannic acid delayed the enrichment of some starch-degrading bacteria. Besides, fermentation of the resistant starch/tannic acid mixtures resulted in more SCFAs, particularly butyrate, and higher abundance of beneficial bacteria, including Bifidobacterium, Faecalibacterium, Blautia and Dorea, than fermentation of resistant starch after 48 h. Thus, it was inferred that tannic acid could delay the metabolism of resistant starch, which was due to its inhibitory effect on the α-amylase activity and regulatory effect on gut microbiota.


Assuntos
Microbioma Gastrointestinal , Polifenóis , Amido Resistente , Humanos , Fermentação , Amido Resistente/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Amido/metabolismo , Bactérias/genética , Bactérias/metabolismo , alfa-Amilases/metabolismo
5.
Int J Biol Macromol ; 246: 125647, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37394221

RESUMO

Fermentation of resistant starch from the starch-ferulic acid inclusion complex, one representative of the starch-polyphenol inclusion complex, was investigated in this study. It was found that this complex-based resistant starch, high-amylose corn starch and the mixture of ferulic acid and high-amylose corn starch were mainly utilized at the initial 6 h as indicated by the gas production and pH. Besides, the supplement of high-amylose corn starch, the mixture and the complex promoted production of short-chain fatty acids (SCFAs), reduced the ratio of Firmicutes/Bacteroidetes (F/B) and selectively stimulated the proliferation of some beneficial bacteria. Specifically, the production of SCFAs in the control and high-amylose starch, mixture and complex groups was 29.33 mM, 140.82 mM, 144.12 mM, and 167.4 mM after fermentation for 48 h, respectively. Moreover, the F/B ratio of those groups was 1.78, 0.78, 0.8 and 0.69, respectively. These results suggested that the supplement of the complex-based resistant starch led to the most SCFAs and the lowest F/B ratio (P < 0.05). Moreover, the complex group had the largest abundance of beneficial bacteria, including Bacteroides, Bifidobacterium and Lachnospiraceae_UCG-001 (P < 0.05). In summary, the resistant starch from the starch-ferulic acid inclusion complex exhibited stronger prebiotic activity than high-amylose corn starch and the mixture.


Assuntos
Amilose , Amido , Amido/metabolismo , Amido Resistente , Zea mays/metabolismo , Fermentação , Ácidos Graxos Voláteis , Bactérias/metabolismo , Firmicutes/metabolismo , Bacteroidetes/metabolismo
6.
Food Funct ; 14(14): 6376-6384, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37335179

RESUMO

Phytoglycogen-derived self-assembled nanoparticles (SMPG/CLA) and enzymatic-assembled nanoparticles (EMPG/CLA) were fabricated for delivery of conjugated linoleic acid (CLA). After measuring the loading rate and yield, the optimal ratio for both assembled host-guest complexes was 1 : 10, and the maximum loading rate and yield for EMPG/CLA were 1.6% and 88.1%, respectively, higher than those of SMPG/CLA. Structural characterization studies showed that the assembled inclusion complexes were successfully constructed, and had a specific spatial architecture with inner-core amorphous and external-shell crystalline parts. A higher protective effect against oxidation of EMPG/CLA was observed than that of SMPG/CLA, supporting efficient complexation for a higher order crystalline structure. After 1 h of gastrointestinal digestion under the simulated conditions, 58.7% of CLA was released from EMPG/CLA, which was lower than that released from SMPG/CLA (73.8%). These results indicated that in situ enzymatic-assembled phytoglycogen-derived nanoparticles might be a promising carrier platform for protection and targeted delivery of hydrophobic bioactive ingredients.


Assuntos
Ácidos Linoleicos Conjugados , Nanopartículas , Interações Hidrofóbicas e Hidrofílicas , Ácidos Linoleicos Conjugados/química , Nanopartículas/química , Oxirredução
7.
Food Chem ; 424: 136373, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37236077

RESUMO

Glucan dendrimers were developed with microbial branching enzyme (BE) treated maltodextrin. The molecular weight (Mw) of recombinant BE was 79.0 kDa, and its optimum activity was observed at pH 7.0 and 70 °C. BE converted different maltodextrins with dextrose equivalent value of 6 (MD6), 12 (MD12), or 19 (MD19) into the given glucan dendrimers, along with the marked increment of the molecular density (approximately 30-60 folds) and α-1,6 linkage percentage (up to 7.3-9.7%). Among three glucan dendrimers, the enzyme-treated MD12 showed a more homogeneous Mw distribution with the maximum Mw of 5.5 × 106 g/mol, indicating that higher substrate catalytic specificity of BE for MD12 substrate. During transglycosylation with MD12 for 24 h, the shorter chains (degree of polymerization, DP < 13) increased from 73.9% to 83.0%, accompanying by a reduction of medium chains (DP13-24) and long chains (DP > 24). Moreover, the slowly digestible and resistant nutritional fractions were increased by 6.2% and 12.5%, respectively. The results suggested that the potentiality of BE structuring glucan dendrimer with tailor-made structure and functionality for industrial application.


Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana , Dendrímeros , Glucanos/química , Dendrímeros/química
8.
Foods ; 12(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37048191

RESUMO

Rice bran, rich in feruloyl arabinoxylan, is a good source of feruloyl oligosaccharides (FOs). To prepare FOs, bran was often hydrolyzed by amylase and protease to remove starch and protein and then hydrolyzed by xylanase, which was time-consuming and had a low yield. To solve the above problems, enzymatic extrusion was used to treat rice bran, and the effects of traditional hydrolysis, a combination of traditional extrusion and hydrolysis (extrusion-hydrolysis) and enzymatic extrusion on the yield of FOs were investigated and compared in this study. It was found that traditional extrusion and enzymatic extrusion significantly increased the yield of FOs. Particularly, the yield of FOs resulting from enzymatic extrusion was increased to 5.78%, while the yield from traditional hydrolysis was 4.23%. Microscopy analysis showed that extrusion damaged the cell wall of bran, which might increase the accessibility of xylanase to arabinoxylan and the yield of FOs. Spectroscopy analysis suggested that FOs obtained by different pretreatments had similar structures. It was obvious that enzymatic extrusion saved the time for removal of starch and protein and increased the yield of FOs. In addition, the highest yield of FOs was found at the moisture content of 30% and the screw speed of 50 rpm. This study provided an efficient method for the preparation of FOs that is suitable for industrial production.

9.
Int J Biol Macromol ; 235: 123887, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36870663

RESUMO

The effect of sodium alginate (SA) on the yogurt stability and the related mechanisms were investigated. It was found that low-concentration SA (≤0.2 %) increased the yogurt stability, while high-concentration SA (≥0.3 %) decreased the yogurt stability. Sodium alginate increased the viscosity and viscoelasticity of yogurt and this effect was positively correlated with its concentration, suggesting that SA worked as the thickening agent in yogurt. However, addition of ≥0.3 % SA damaged the yogurt gel. These results suggested that interaction between milk protein and SA might play an important role in the yogurt stability besides the thickening effect. Addition of ≤0.2 % SA did not change the particle size of casein micelles. However, addition of ≥0.3 % SA induced aggregation of casein micelles and increased the size. And the aggregated casein micelles precipitated after 3 h storage. Isothermal titration calorimetry analysis showed that casein micelles and SA were thermodynamically incompatible. These results suggested that the interaction between casein micelles and SA induced aggregation and precipitation of casein micelles, which was critical in the destabilization of yogurt. In conclusion, the effect of SA on the yogurt stability was dependent on the thickening effect and the interaction between casein micelles and SA.


Assuntos
Caseínas , Micelas , Caseínas/química , Iogurte/análise , Proteínas do Leite/química , Tamanho da Partícula
10.
J Sci Food Agric ; 103(1): 83-91, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35792714

RESUMO

BACKGROUND: Worldwide, fried food has a huge demand and good development prospects. Low oil in foods is the standard that everyone is now pursuing for a healthy diet. RESULTS: The oil absorption behavior of rice starch during frying was investigated in the presence or absence of fatty acids or fatty acid esters with different carbon chain lengths. The complex formed between starch and fatty acids or fatty acid esters was dependent on lipid chain length, which was confirmed by X-ray diffraction and complexing index. The formation of starch-lipid complexes could significantly reduce the oil absorption of starch, and the complexes with higher complexing index had lower oil absorption. The starch-palmitic acid complex showed the lowest oil absorption after frying, which was 14.06 g per 100 g lower than that of gelatinized starch. This was attributed to the ability of the palmitic acid to increase the density of starch crystalline polymorphs as well as their ability to complex with the amylose spiral cavity. CONCLUSION: These results may be useful for development of healthier fried starch-based foods with reduced oil contents. © 2022 Society of Chemical Industry.


Assuntos
Amilose , Amido , Amido/química , Amilose/química , Ácidos Graxos/química , Ácidos Palmíticos , Ésteres
11.
Food Chem ; 372: 131332, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34818742

RESUMO

Poor solubility of proteins negatively affects their functional properties and greatly limits their application. Enzymatic cross-linking with polysaccharides can improve solubility and functional properties of proteins. The enzymes used include transglutaminase, laccase and peroxidase. Therefore, this work introduces the cross-linking mechanisms of these enzymes and the characterization techniques, the improved properties and the potential applications of the enzymatically-synthesized protein-polysaccharide conjugate. Transglutaminase catalyzes the formation of a new peptide bond and thus works on amino-containing polysaccharides to conjugate with proteins. However, laccase and peroxidase catalyze oxidation of various compounds with phenol and aniline structures. Therefore, these two enzymes can catalyze the conjugate reaction between proteins and feruloylated polysaccharides which are widely distributed in cereal bran. Compared with the unmodified protein, the enzymatically-synthesized protein-polysaccharide conjugate usually has higher solubility and better functional properties. Thus, it is inferred that enzymatic conjugation with polysaccharide molecules can extend the application of proteins.


Assuntos
Polissacarídeos , Proteínas , Lacase , Oxirredução , Solubilidade
12.
Brain ; 144(11): 3421-3435, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34918046

RESUMO

Huntington's disease is an autosomal-dominant neurodegenerative disease caused by CAG expansion in exon 1 of the huntingtin (HTT) gene. Since mutant huntingtin (mHTT) protein is the root cause of Huntington's disease, oligonucleotide-based therapeutic approaches using small interfering RNAs (siRNAs) and antisense oligonucleotides designed to specifically silence mHTT may be novel therapeutic strategies for Huntington's disease. Unfortunately, the lack of an effective in vivo delivery system remains a major obstacle to realizing the full potential of oligonucleotide therapeutics, especially regarding the delivery of oligonucleotides to the cortex and striatum, the most severely affected brain regions in Huntington's disease. In this study, we present a synthetic biology strategy that integrates the naturally existing exosome-circulating system with artificial genetic circuits for self-assembly and delivery of mHTT-silencing siRNA to the cortex and striatum. We designed a cytomegalovirus promoter-directed genetic circuit encoding both a neuron-targeting rabies virus glycoprotein tag and an mHTT siRNA. After being taken up by mouse livers after intravenous injection, this circuit was able to reprogramme hepatocytes to transcribe and self-assemble mHTT siRNA into rabies virus glycoprotein-tagged exosomes. The mHTT siRNA was further delivered through the exosome-circulating system and guided by a rabies virus glycoprotein tag to the cortex and striatum. Consequently, in three mouse models of Huntington's disease treated with this circuit, the levels of mHTT protein and toxic aggregates were successfully reduced in the cortex and striatum, therefore ameliorating behavioural deficits and striatal and cortical neuropathologies. Overall, our findings establish a convenient, effective and safe strategy for self-assembly of siRNAs in vivo that may provide a significant therapeutic benefit for Huntington's disease.


Assuntos
Engenharia Genética/métodos , Terapia Genética/métodos , Proteína Huntingtina , Doença de Huntington , RNA Interferente Pequeno , Animais , Exossomos/metabolismo , Fígado/metabolismo , Camundongos , RNA Interferente Pequeno/farmacologia , Transfecção
13.
Foods ; 10(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34828934

RESUMO

The pH-responsive hydrogels were obtained through successive carboxymethylation and phosphorylase elongatation of phytoglycogen and their structure and functional characterizations were investigated. Phytoglycogen (PG) was first carboxymethylated to obtain carboxymethyl phytoglycogen (CM-PG) with degree of substitution (DS) at 0.15, 0.25, 0.30, and 0.40, respectively. Iodine staining and X-ray diffraction analysis suggested that the linear glucan chains were successfully phosphorylase-elongated from the non-reducing ends at the CM-PG surface and assembled into the double helical segments, leading to formation of the hydrogel. The DS of CM-PG significantly influenced elongation of glucan chains. Specifically, fewer glucan chains were elongated for CM-PG with higher DS and the final glucan chains were shorter, resulting in lower gelation rate of chain-elongated CM-PG and lower firmness of the corresponding hydrogels. Scanning electron microscope observed that the hydrogels exhibited a porous and interconnected morphology. The swelling ratio and volume of hydrogels was low at pH 3-5 and then became larger at pH 6-8 due to electrostatic repulsion resulting from deprotonated carboxymethyl groups. Particularly, the hydrogel prepared from chain-elongated CM-PG (DS = 0.25) showed the highest sensitivity to pH. These results suggested that phosphorylase-treated CM-PG formed the pH-responsive hydrogel and that the elongation degree and the properties of hydrogels depended on the carboxymethylation degree. Thus, it was inferred that these hydrogels was a potential carrier system of bioactive substances for their targeted releasing in small intestine.

14.
BMC Infect Dis ; 21(1): 583, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134659

RESUMO

BACKGROUND: Previous studies showed that type 2 short bowel syndrome (SBS) rats were accompanied by severe intestinal bacterial dysbiosis. Limited data are available for intestinal fungal dysbiosis. Moreover, no effective therapeutic drugs are available for these microbiota dysbiosis. The aims of our study were to investigate the therapeutic potential of glucagon-like peptide 2 (GLP-2) for these microbiota dysbiosis in type 2 SBS rats. METHODS: 8-week-old male SD rats which underwent 80% small bowel resection, ileocecum resection, partial colon resection and jejunocolostomy, were treated with saline (SBS group, n = 5) or GLP-2 (GLP2.SBS group, n = 5). The Sham group rats which underwent transection and re-anastomosis were given a saline placebo (Sham group, n = 5). 16S rRNA and ITS sequencing were applied to evaluate the colonic bacterial and fungal composition at 22 days after surgery, respectively. RESULTS: The relative abundance of Actinobacteria, Firmicutes and proinflammatory Proteobacteria increased significantly in SBS group rats, while the relative abundance of Bacteroidetes, Verrucomicrobia and Tenericutes decreased remarkably. GLP-2 treatment significantly decreased Proteus and increased Clostridium relative to the saline treated SBS rats. The diversity of intestinal fungi was significantly increased in SBS rats, accompanied with some fungi abnormally increased and some resident fungi (e.g., Penicillium) significantly decreased. GLP-2 treatment significantly decreased Debaryomyces and Meyerozyma, and increased Penicillium. Moreover, GLP-2 partially restored the bacteria-fungi interkingdom interaction network of SBS rats. CONCLUSION: Our study confirms the bacterial and fungal dysbiosis in type 2 SBS rats, and GLP-2 partially ameliorated these microbiota dysbiosis.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Peptídeo 2 Semelhante ao Glucagon/farmacologia , Intestinos/microbiologia , Síndrome do Intestino Curto/patologia , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Animais , Colo/cirurgia , Colostomia , Análise Discriminante , Modelos Animais de Doenças , Disbiose , Fungos/genética , Fungos/isolamento & purificação , Peptídeo 2 Semelhante ao Glucagon/uso terapêutico , Análise dos Mínimos Quadrados , Masculino , Análise de Componente Principal , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/metabolismo , Ratos , Ratos Sprague-Dawley , Síndrome do Intestino Curto/tratamento farmacológico , Síndrome do Intestino Curto/microbiologia
15.
Food Chem ; 358: 129856, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933975

RESUMO

W/O/W emulsions were easily prepared by oleogelation of the oil phase using rice bran wax (RBX) and their microstructure, stability, rheology and protection of proanthocyanidins and ß-carotene were investigated. Formation of the W/O/W emulsion was confirmed using confocal laser scanning microscopy and staining of the inner aqueous phase by tartrazine. The average particle size and viscosity of the emulsion increased as the RBX concentration increased. Moreover, RBX increased the stability of the emulsion and the emulsion was the most stable when the RBX concentration was 8.0% or 10.0%. On the other hand, the W/O/W emulsions were used to simultaneously encapsulate proanthocyanidins and ß-carotene. Specifically, proanthocyanidins and ß-carotene in RBX-containing emulsions were more stable and had higher bioaccessibility than in the emulsion without RBX. Besides, both their chemical stability and bioaccessibility reached the maximum value when the RBX concentration was 8.0% or 10.0%. In summary, the optimal RBX concentration was 8.0%.


Assuntos
Emulsões/química , Proantocianidinas/química , Óleo de Farelo de Arroz/química , beta Caroteno/química , Óleo de Milho/química , Armazenamento de Alimentos , Tamanho da Partícula , Proantocianidinas/farmacocinética , Reologia , Viscosidade , Água/química , beta Caroteno/farmacocinética
16.
Cell Res ; 31(6): 631-648, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33782530

RESUMO

RNAi therapy has undergone two stages of development, direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands; both have not solved the problem of efficient in vivo siRNA delivery. Here, we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes. By combination of different genetic circuit modules, in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues (e.g., brain), inducing potent target gene silencing in these tissues. The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases, including EGFR/KRAS in lung cancer, EGFR/TNC in glioblastoma and PTP1B in obesity. Overall, our strategy represents a next generation RNAi therapeutics, which makes RNAi therapy feasible.


Assuntos
Glioblastoma , Terapêutica com RNAi , Inativação Gênica , Humanos , Interferência de RNA , RNA Interferente Pequeno/genética
17.
PLoS One ; 16(2): e0245832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529238

RESUMO

HER2 amplification greatly contributes to the tumorigenesis of multiple cancers. Intronic miR-4728-5p is transcribed along with its host gene HER2. However, little is known about the role of miR-4728-5p in cancer. This study aims to elucidate the potential role of miR-4728-5p and the underlying mechanism in breast cancer. Kaplan-Meier analysis showed that higher expression of HER2 led to worse survival outcomes in breast cancer patients. The TCGA dataset revealed that compared to normal breast tissues, HER2 and miR-4728-5p levels were significantly upregulated in breast cancer tissues with a positive correlation. In functional assays, miR-4728-5p was confirmed to promote the proliferation and migration in breast cancer cell BT474. EBP1 was identified as a direct target of miR-4728-5p via bioinformatics and luciferase reporter assays. miR-4728-5p was further demonstrated to increase HER2 expression and promote cell proliferation and migration by directly inhibiting EBP1 in breast cancer. Taken together, the HER2-intronic miR-4728-5p/EBP1/HER2 feedback loop plays an important role in promoting breast cancer cell proliferation and migration. Our study provides novel insights for targeted therapies of breast cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular/genética , Íntrons/genética , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Receptor ErbB-2/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Humanos , Estimativa de Kaplan-Meier , Células MCF-7
18.
Bioorg Chem ; 105: 104390, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33137555

RESUMO

As an essential enzyme with a variety of physiological functions, Cyclooxygenase-2 (COX-2) is also closely related to carcinoma due to the observed overexpression. In this work, a novel series of sulfonamide-containing aminophosphonate derivatives (A1-A25) were developed as selective COX-2 inhibitors and anti-cancer candidates. The top hit compound A23 presented applicative COX-2 inhibitory activity (IC50 = 0.28 µM) and anti-proliferative capability against several cancer cell lines (IC50 = 2.34-16.43 µM for HeLa, MCF-7, HCT116 and HepG2 cells). Among them, A23 has the most significant inhibitory effect on HCT116 cells, which were comparable with that of the positive controls respectively (eg: IC50 = 8.73 µM for HCT116). The binding pattern of A23 was inferred by the molecular docking simulation. Moreover, A23 could induce the apoptosis via a mitochondrion-dependent mode and cause the arrest of the cell-cycle in G1 stage. A further investigation in the checkpoints of apoptosis indicated that the node Bcl-2 might connect the selective COX-2 inhibition and the anti-tumor activity. Therefore, this work brought new information for developing COX-2 inhibitors in anti-tumor therapies in future.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Descoberta de Drogas , Organofosfonatos/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Organofosfonatos/síntese química , Organofosfonatos/química , Relação Estrutura-Atividade , Sulfonamidas/química
19.
Int J Biol Macromol ; 164: 3496-3500, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32890568

RESUMO

Annealing behavior of amylose and amylopectin was unclear. In this work, high purity amylose and amylopectin were extracted from rice starch, and structural properties of the retrograded rice starch, amylose, and amylopectin before and after annealing treatment were explored. It was found that the purity of the amylose and amylopectin was 95.64% ±â€¯2.69% and 94.98% ±â€¯0.97%, respectively. Their molecular weight was (2.93 ±â€¯0.21) × 106 Da and (5.90 ±â€¯0.13) × 107 Da, respectively. Besides, the relative crystallinities and ratios of 1047 cm-1/1022 cm-1 of the retrograded rice starch and amylose were significantly increased by annealing treatment, while that of retrograded amylopectin did not change. These results clarified that amylose was more sensitive to annealing treatment than amylopectin, and amylose was more responsible for annealing of starch than amylopectin. The findings contributed to a better understanding of the annealing behavior of starch.


Assuntos
Amilopectina/química , Amilopectina/isolamento & purificação , Amilose/química , Amilose/isolamento & purificação , Oryza/química , Amido/química , Fracionamento Químico , Fenômenos Químicos , Peso Molecular , Análise Espectral
20.
Food Funct ; 11(8): 7037-7047, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32812985

RESUMO

This work describes the reuteransucrase-catalyzed reaction and structural characterization as well as in vitro fermentation for the acceptor products of gluco-oligomers from sucrose and maltose. At a low concentration of sucrose, the production of gluco-oligomers was favored, resulting in a relatively large number of acceptor products (DP3-5). A mathematical model was also proposed to simulate gluco-oligomer production depending on the reaction conditions. The fine structures of major linear gluco-oligomer fractions for a sucrose : maltose ratio of 1 : 1 were assigned as follows: α-d-Glcp-(1→6)-α-d-Glcp-(1→4)-d-Glcp, α-d-Glcp-(1→4)-α-d-Glcp-(1→4)-α-d-Glcp-(1→4)-d-Glcp, α-d-Glcp-(1→4)-α-d-Glcp-(1→6)-α-d-Glcp-(1→4)-d-Glcp, and α-d-Glcp-(1→6)-α-d-Glcp-(1→4)-α-d-Glcp-(1→6)-α-d-Glcp-(1→4)-d-Glcp, respectively. Compared with dextran and GOS57, the results of fermentation selectivity indicated that gluco-oligomers promoted the proliferation of gut bacteria and total SCFA production with a higher concentration of propionate. These data suggested that the gluco-oligomers synthesized via the reuteransucrase acceptor reaction had a prebiotic effect on gastrointestinal health.


Assuntos
Oligossacarídeos/química , Prebióticos , Catálise , Fezes/química , Fermentação , Maltose/química , Sacarose/química
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