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1.
Exp Dermatol ; 31(2): 122-132, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34270128

RESUMO

Reportedly, decreases in fatty acid (FA) chain length of ceramide (CER) are associated with interferon-γ (IFN-γ), which shows increased expression in psoriasis. However, the underlying mechanism of this association remains unclear. Therefore, in this study, we aimed to clarify this association between FA chain length of CER, IFN-γ, and the major transcriptional factors involving psoriasis. CER profiling according to FA chain length and class was performed in murine epidermis (n = 10 BALB/c mice topically treated with imiquimod, n = 10 controls) and human stratum corneum (SC) (n = 12 psoriasis, n = 11 controls). The expression of lipid synthetic enzymes, including elongases (ELOVLs), in murine epidermis was also measured using RT-PCR. Furthermore, the association of IFN-γ with various enzymes and transcription factors involved in the generation of long-chain CERs was also investigated using in vitro keratinocyte. A significant decrease in the percentage of long-chain CERs was observed in psoriasis-like murine epidermis and human psoriatic SC. Additionally, the expression levels of ELOVL1, ELOVL4, and ceramide synthase3 (CerS3) were significantly decreased in psoriasis-like murine epidermis and IFN-γ-treated keratinocyte. There was also a significant decrease in the expression of transcriptional factors, including peroxisome proliferator-activated receptor (PPAR), in IFN-γ treated keratinocyte. Thus, it could be suggested that IFN-γ may regulate ELOVL and CerS levels by down-regulating the transcriptional factors. Additionally, given the possible involvement of PPARs or liver X receptor agonist in the CER elongation process, they may serve as potential therapeutic agents for lengthening the CER FAs in psoriasis.


Assuntos
Ceramidas , Psoríase , Animais , Ceramidas/metabolismo , Epiderme/metabolismo , Ácidos Graxos/metabolismo , Interferon gama/metabolismo , Camundongos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Psoríase/tratamento farmacológico , Psoríase/metabolismo
2.
J Sci Food Agric ; 102(15): 7239-7248, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35730731

RESUMO

BACKGROUND: The structural and digestion properties of starch-lipid complexes are closely related to the properties of lipids. The chain length and degree of unsaturation of fatty acids (FAs), which can affect the structural and digestion properties of starch-lipid nanocomplexes, therefore need to be examined in detail to gain a better understanding of this. In this study, the effects of chain length (10-18 carbons) and degree of unsaturation (0-2) of FA on the structural and in vitro starch digestion properties of high amylose corn starch (HAS)-FA nanocomplexes were investigated, as was the correlation between their structural alterations and digestibility. RESULTS: This study showed that HAS-FA nanocomplexes with 10-carbon (38.55%) and 12-carbon (44.56%) FAs displayed high-resistant starch (RS) and slowly digestible starch (SDS) content, whereas those with 18-carbon FAs with two double bonds exhibited low RS + SDS content (23.41%). The complexing index, R1047/1022 , relative crystallinity, and enthalpy change in the HAS-FA nanocomplexes also increased with the reduction in the chain length (except for 10-carbon FA) and the degree of unsaturation of FAs, whereas the equilibrium hydrolysis percentage, kinetic constant and apparent amylose content showed an opposite trend. CONCLUSION: Chain length and degree of unsaturation of FAs affected the digestibility of HAS-FA nanocomplexes. The HAS-FA nanocomplexes with 12-carbon FAs displayed high RS + SDS content with higher degrees of molecular order at long-range and short-range levels. Results provided guidelines to regulate the digestibility of starch-fatty acid nanocomplexes by varying the FA structures. © 2022 Society of Chemical Industry.


Assuntos
Amilose , Amido , Amido/química , Amilose/química , Ácidos Graxos , Digestão , Carbono
3.
Am J Physiol Gastrointest Liver Physiol ; 307(3): G381-9, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24924750

RESUMO

Fatty acids that vary in chain length and degree of unsaturation have different effects on metabolism and human health. As evidence for a "taste" of nonesterified fatty acids (NEFA) accumulates, it may be hypothesized that fatty acid structures will also influence oral sensations. The present study examined oral sensitivity to caproic (C6), lauric (C12), and oleic (C18:1) acids over repeated visits. Analyses were also conducted on textural properties of NEFA emulsions and blank solutions. Oral thresholds for caproic acid were lower compared with oleic acid. Lauric acid thresholds were intermediate but not significantly different from either, likely due to lingering irritating sensations that prevented accurate discrimination. From particle size analysis, larger droplets were observed in blank solutions when mineral oil was used, leading to instability of the emulsion, which was not observed when emulsions contained NEFA or when mineral oil was removed from the blank. Rheological data showed no differences in viscosity among samples except for a slightly higher viscosity with oleic acid concentrations above 58 mM. Thus, texture was unlikely to be the property used to distinguish between the samples. Differences in oral detection and sensation of caproic, lauric, and oleic acids may be due to different properties of the fatty acid alkyl chains.


Assuntos
Ácidos Graxos/administração & dosagem , Boca/inervação , Limiar Gustativo , Administração Oral , Adulto , Caproatos/administração & dosagem , Estudos Cross-Over , Emulsões , Ácidos Graxos/química , Feminino , Humanos , Ácidos Láuricos/administração & dosagem , Masculino , Óleo Mineral/administração & dosagem , Estrutura Molecular , Ácido Oleico/administração & dosagem , Tamanho da Partícula , Reologia , Relação Estrutura-Atividade , Viscosidade , Adulto Jovem
4.
Int J Pharm ; 658: 124176, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38688427

RESUMO

The aim of this study was to evaluate the enhanced thermal stability and physicochemical properties of fattigated vaccine antigens. High molecular weight influenza hemagglutinin (Heg) was used as a model antigen because of low heat stability requiring cold chamber. Heg was conjugated with long-chain oleic acid (C18) and short-chain 3-decenoic acid (C10) to prepare fattigated Heg. Circular dichroism analysis revealed no significant changes in the three-dimensional structure post-conjugation. In the liquid state, the fattigated Heg was self-assembled into nanoparticles (NPs) due to its amphiphilic nature, with sizes of 136.27 ± 12.78 nm for oleic acid-conjugated Heg (HOC) and 88.73 ± 3.27 nm for 3-decenoic acid-conjugated Heg (HDC). Accelerated thermal stability studies at 60 °C for 7 days demonstrated that fattigated Heg exhibited higher thermal stability than Heg in various liquid or solid states. The longer-chained HOC showed better thermal stability than HDC in the liquid state, attributed to increased hydrophobic interactions during self-assembly. In bio-mimicking liquid states at 37 °C, HOC exhibited higher thermal stability than Heg. Furthermore, solid-state HOC with cryoprotectants (trehalose, mannitol, and Tween® 80) had significantly increased thermal stability due to reduced exposure of protein surface area via nanonization behavior. The current fattigation platform could be a promising strategy for developing thermostable nano vaccines of heat-labile vaccine antigens.


Assuntos
Estabilidade de Medicamentos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Nanopartículas , Nanopartículas/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/química , Vacinas contra Influenza/administração & dosagem , Ácido Oleico/química , Vacinas Conjugadas/química , Ácidos Graxos/química , Temperatura Alta , Tamanho da Partícula , Polissorbatos/química , Interações Hidrofóbicas e Hidrofílicas , Ácidos Graxos Monoinsaturados/química , Antígenos/química , Antígenos/imunologia
5.
Int J Biol Macromol ; 230: 123415, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36708900

RESUMO

To evaluate the effect of elaborate difference in the hydrophobicity of core material on encapsulation process and physicochemical properties of the composites, composites of starch and FA with various chain lengths (C:12-22) were prepared via nanoprecipitation. X-ray diffraction analyses revealed that all composites had a Vh-amylose crystalline unit cell, but the chain length of FA did not induce a clear change in crystallinity or the hydrodynamic mean diameter of the composites. As the chain length of FA increased from 12 to 22, FA content in the composites increased from 1.69 to 14.85 mg/g composite. The absorption analyses of Rose Bengal on the composite surfaces revealed that their hydrophobicity increased with increasing chain length of FA. The incorporation of FA enhanced the emulsification activity of the composites, and this result revealed that the composites could be applied as an emulsification agent. For longer FA, composite storage stability increased, but the release of FA by in vitro digestion was delayed.


Assuntos
Nanocompostos , Amido , Amido/química , Ácidos Graxos , Amilose/química , Cristalografia por Raios X , Nanocompostos/química , Difração de Raios X
6.
Int J Nanomedicine ; 18: 7115-7131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38054081

RESUMO

Background: Quetiapine (QTP) is a first-line antipsychotic drug, but its therapeutic druggability and patient adherence were limited due to high oral dose strength, low bioavailability and physicochemical/biopharmaceutical issues. Purpose: To investigate the roles of fatty acid chain length and enzyme-oriented QTP controlled release from pH-triggering self-assembled fatty acid conjugated QTP nanosuspensions (NSPs). Methods: QTP was conjugated with different chain length fatty acids (C10-decanoic acid, C14-myristic acid, C18-stearic acid) to obtain QTP-fatty acid conjugates (QFCs: QD, QM, QS) by exploiting 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/4-dimethylaminopyridine (EDC/DMAP) conjugation chemistry. Then, the solubility, partitioning coefficient (log P), cell viability and cleavage kinetics of QFCs were evaluated. The pH-triggering self-assembled behaviors of QFCs to form QTP-fatty acid NSPs (QDN, QMN, QSN) by varying pH, QFC concentration and proton-to-QTP ratios were characterized. The morphological images, critical micelle concentration (CMC), physicochemical properties and enzyme-oriented QTP controlled release of NSPs were examined. Results: Three QFCs were synthesized with different chain length fatty acids from QTP after desalting fumarate from QTP fumarate. The pH, QFC concentration and proton-to-quetiapine molar ratio could influence physicochemical properties and nanonization behaviors of QFCs. All three QFCs showed no effect on the viability of myoblast cells. The pH-triggering self-assembly of amphiphilic QFCs to form nanoparticles (NPs) occurred as the amine moiety of QTP was readily ionized in a strongly acidic environment (pH 1.2). Interestingly, the longer the fatty acid chain length, the lower water solubility, the higher log P (lipophilicity) and the smaller NP particle size were observed. The conversion rate of QFCs to liberate QTP by esterase in human plasma and liver S9 fractions was also inversely proportional to the fatty acid carbon chain length. Interestingly, the freeze-dried QMN showed the esterase-oriented controlled release of QTP over one month, unlike the initial burst release of QDN or the slowly delayed release pattern of QSN. Conclusion: A new pH-triggering self-assembled nanonization platform was developed using different chain length fatty acid conjugated QTP in low pH environment. By varying fatty acid chain length, the enzyme-oriented QTP controlled release dosage form was challenged to enhance the therapeutic effectiveness of QTP.


Assuntos
Ácidos Graxos , Prótons , Humanos , Fumarato de Quetiapina , Preparações de Ação Retardada , Concentração de Íons de Hidrogênio , Esterases , Fumaratos
7.
Int J Nanomedicine ; 18: 2325-2344, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168738

RESUMO

Background: Leuprolide (LEU), a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH), could exert a direct inhibitory activity on the proliferation of prostate cancer cells. However, the short half-life in blood and the biopharmaceutical problem of LEU limit this anticancer activity. Purpose: To improve its druggability for improving anticancer activity, the amine-group targeted LEU was conjugated with different chain lengths of saturated fatty acids (FAs). Methods: LEU-fatty acid conjugates (LFCs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry. The physicochemical properties and the self-assembled behaviors of the conjugates were extensively investigated. The in vitro anticancer activity of three LFCs was extensively studied in both 2D monolayer and 3D spheroid culture models of a prostate cancer cell line, PC3. Results: Three LFCs could be readily self-assembled into nanoparticles (LFNs) with a small size of around 100 nm, positive charges, and exhibited greater permeability rates compared to the same concentration of LEU, excluding LSN. The chain length of FA in conjugate was positively related to the selectivity index between cancer cells and non-cancerous cell lines. All LFCs showed a superior direct antiproliferative effect on cancer cells in the following order: LSC (98.9%) > LPC (86.7%) > LLC (75.0%) > LEU (8.9%) after repeat daily of the same dose strength of LEU for 4 days. In addition, the 3D spheroid model study indicates that all LFCs with a one-time treatment performed a long-acting inhibitory effect on tumor growth as compared to LEU after 7 days. Conclusion: The conjugation of LEU with different chain lengths of FAs could provide a novel strategy to improve peptide stability and exert an additional superior direct inhibitory effect for the treatment of several hormone-responsive tumor systems using therapeutic peptides.


Assuntos
Produtos Biológicos , Neoplasias da Próstata , Masculino , Humanos , Leuprolida/farmacologia , Ácidos Graxos , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral
8.
Food Res Int ; 155: 111119, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35400405

RESUMO

The main objectives of our work were to produce new nanostructured lipid carriers (NLCs) from interesterified and simple lipid phases and to study the influence of lipid composition on the physical characteristics and stability of NLCs. We used conventional oils and fats already used in lipid-based foods, in addition to soy lecithin as a natural emulsifier. The NLCs were formulated using as lipid phase, simple and interesterified blends composed of soybean oil as liquid lipid and fully hydrogenated oils from palm, soybean, microalgae, and crambe as solid lipids. NLCs were produced using high-pressure homogenization. NLCs were influenced by chemical interesterification and by the composition of the solid lipid used, mainly in relation to the fatty acid chain size. NLC formulations developed with a simple lipid phase were 256-323 nm (d32) in size, with zeta potential values ranging from -36.93 to -42.87 mV after 60 days of storage. NLCs developed with the interesterified lipid phase were 250-288 nm (d32) in size, with zeta potential values ranging from -40.17 to -44.20 mV after 60 days of storage. NLCs produced with saturated fatty acids with larger chain sizes showed larger particle sizes but showed less variation in this parameter over storage. Interesterification reduced the melting temperature of NLCs, indicating decreased crystallinity and a less organized structure. Moreover, interesterification favored crystals in the ß' form, which is a positive characteristic for incorporating bioactive compounds. Thus, the systems developed in this study are innovative, mainly in terms of the composition of the NLCs, and have good potential for food applications.


Assuntos
Nanoestruturas , Ácidos Graxos , Tamanho da Partícula , Óleos de Plantas/química , Óleo de Soja/química
9.
Food Res Int ; 157: 111208, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761530

RESUMO

In this work, we studied the influence of fatty acid chain length and crystallization temperature on the crystallization behavior during the storage of binary blends modified by chemical interesterification. The blends were produced with soybean oil and fully hydrogenated oils from palm kernel, palm, soybean, microalgae, and crambe, evaluated separately, at a ratio of 50:50 (% w/w). The blends were crystallized by two crystalline stabilization methods. In method I, the samples were maintained at 25 °C for 24 h before the analyses. In method II, the samples were maintained at 5 °C for 24 h, followed by crystalline stabilization at 25 °C for 24 h before the analyses. The interesterification reaction caused considerable changes in the TAGs profile with increasing asymmetric TAGs. These TAGs changes promoted an increase in the crystallization induction time, a decrease in the maximum solids content, and changes in crystals morphology. The increase in the FAs chain length promoted the increased nucleation rate that influenced morphology crystals. Method II promoted a reduction in the medium diameter of crystals and the appearance of the ß phase with storage time. For crystallization carried out at higher temperatures (method I), we observed that ß' was favored. Unusual polymorphic transitions were observed with storage time in samples with higher tristearin content. We identified clear correlations between the predominance of ß' phase in the interesterified blends and TAGs of S2U and SU2-type. In addition, the blends with a more diverse range of fatty acids concerning chain size also showed the ß' polymorph. ß polymorph, on the other hand, was associated with symmetric TAGs, S3 and U3, and CN-54 type TAG. In this study, we used the Rietveld method to quantify the polymorphs and amorphous content in the blends before and after the randomization reaction. This approach allowed a deeper understanding of the crystalline behavior in the blends, which would be difficult to achieve by performing only a visual analysis of the X-ray diffractograms.


Assuntos
Ácidos Graxos , Óleos de Plantas , Cristalização , Ácidos Graxos/química , Óleos de Plantas/química , Óleo de Soja/química
10.
J Food Biochem ; 45(4): e13664, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33598998

RESUMO

We investigated the effect of the chain length and the degree of saturation of fatty acids in dietary triglycerides on serum lipid profiles and hepatic lipid metabolism in Wistar rats. Fat component of the basal diet (soybean oil) was replaced with fats with fatty acids of different chain lengths and saturation and the serum lipids were monitored for 150 days. Principal component (PC) analysis of serum lipid components was related to chain length and saturation. The combined effect of chain length and saturation on PC 1 scores was evaluated by multiple regression analysis. The results indicated that average chain length of the fatty acids of triglycerides has a higher influence on the quality of serum lipid parameters than the average degree of saturation. Expression of selected genes responsible for lipid metabolism showed similar trends in medium chain saturated and long chain polyunsaturated diet groups. PRACTICAL APPLICATIONS: Dietary lipids contain a wide range of saturated and unsaturated fatty acids with different chain lengths. Overall contribution of these different fatty acids decides the health effects of the lipids in the diet. Present study shows that the fats with medium chains and higher degree of saturation and fats with long chains and higher degree of unsaturation (lower degree of saturation) affect serum lipid parameters and expression of hepatic genes involved in the lipid metabolism in a similar manner. Such information is important for physicians to plan dietary schemes to improve the nutritional health and manage the noncommunicable diseases.


Assuntos
Ácidos Graxos , Metabolismo dos Lipídeos , Animais , Dieta , Ratos , Ratos Wistar , Triglicerídeos
11.
Int J Biol Macromol ; 160: 245-251, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32442566

RESUMO

In this study, the effects of various fatty (including caprylic, lauric, and palmitic) acids on physicochemical, mechanical, and barrier properties of basil seed gum (BSG)-based edible films were investigated. The introduction of fatty acids (FAs) into the BSG-based matrix was confirmed by FT-IR. Increasing the FA chain length resulted in an increase in the thickness and opacity of FA-modified BSG films, while water solubility decreased. The water vapor permeability (WVP) of FA-modified films was significantly (P < 0.05) lower than that of control film. The mechanical properties and color attributes of edible films were improved after incorporating caprylic and lauric acids. SEM micrographs revealed a more homogenous microstructure with a higher surface density in the films incorporated with caprylic acid, while a higher roughness and insoluble particles were observed in those incorporated with lauric, and palmitic acids. Our findings showed that lauric acid is a good candidate for improving the barrier and textural characteristics of BSG-based edible films.


Assuntos
Ácidos Graxos/química , Ocimum basilicum/química , Gomas Vegetais/química , Sementes/química , Filmes Comestíveis , Ácidos Láuricos/química , Permeabilidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Vapor , Água/química
12.
Eur J Pharm Biopharm ; 152: 257-269, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32422167

RESUMO

This study aimed to design the ideal nanonizing vehicle for poorly water-soluble model curcumin (CCM) using fattigation-platform nanotechnology, and to investigate the effects of fatty acid salts chain length on nanonizing CCM and its efficient delivery to different cancer cells. HSA-fatty acid conjugates were synthesized by EDC/NHS coupling. Fattigation-platform nanomicelles (NMs), prepared by film hydration, exhibited uniform and spherical morphology, although, each NM varied in particle size, zeta potential, and critical micelle concentration according to the types of fatty acid. Preliminary solubility studies of albumin conjugates with 5 types of fatty acid salts of different chain lengths revealed that C14 exhibited the highest solubilization of CCM. CCM-loaded HSA-C14 NMs demonstrated the highest drug content (5.35 ± 0.48%) and loading efficiency (95.93 ± 1.87%) compared to other NMs. It exhibited enhanced drug release rate and reduced micelle size in biorelevant dissolution medium. Interestingly, this solubilization approach was well applied in poorly water-soluble docetaxel trihydrate (DTX). Preliminary solubility results of DTX was also corresponded to the stable nanonization phenomenon in biorelevant dissolution medium. Compared to the CCM EtOH solution, HSA-C14 NMs showed higher internalization in cancer cell lines A549 and MCF-7, and consequently, exhibited significantly increased cytotoxicity against both cell lines. Therefore, this study provides a new solubilization approach for poorly water-soluble drugs using fatty acid salts of different chain lengths and their micellar formations via nanonization, which could be a promising tool for targeted cancer therapy using poorly water-soluble drugs.


Assuntos
Albuminas/química , Portadores de Fármacos/química , Ácidos Graxos/química , Nanopartículas/química , Água/química , Células A549 , Linhagem Celular , Linhagem Celular Tumoral , Curcumina/química , Docetaxel/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Células HEK293 , Humanos , Células MCF-7 , Micelas , Nanotecnologia/métodos , Tamanho da Partícula , Solubilidade
13.
J Control Release ; 324: 55-68, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32380202

RESUMO

The aims of this study were to design different chain length fatty acid-conjugated albumin nanoparticles (ANPs) and evaluate their anticancer activity in the HCT116 human colorectal cancer xenograft mouse model. Doxorubicin hydrochloride (DOX·HCl) was chosen as a model drug. The different chain lengths of fatty acids (butyric acid; C4, and stearic acid; C18) in albumin conjugates exhibited different physicochemical properties and anticancer activity. Fatty acid-conjugated albumin aided the formation of self-assembled structures with an average size of approximately 200 nm and a negative charge when incubated with excess DOX in an aqueous solution. DOX-loaded long-chain C18-conjugated ANPs allowed efficient encapsulation of hydrophobic DOX into the core of the self-assembled structure, enabling higher drug loading, enhanced colloidal stability and controlled release behavior in PBS pH 7.4 medium as compared with free DOX·HCl or non-fatty acid conjugated ANPs. Furthermore, DOX-loaded fatty acid-conjugated ANPs showed an increased cellular uptake intensity and cytotoxic effects in vitro. In vivo, HCT116 xenograft model experiments confirmed that DOX-loaded C18-conjugated ANPs showed improved anticancer activity and reduced side effects compared with the DOX-treated groups. The long-chain fatty acid-conjugated ANPs synergistically activated the interaction with the free-fatty acid receptor (FFAR) on HCT116 colorectal cancer cells as compared with short-chain C4 or other non-conjugated ANPs. Specifically, DOX-loaded C18-conjugated NPs exhibited significant performance to overexpressed FFAR4 on HCT116 colorectal cancer cells. The fatty acid chain length in the fattigation-platform system could be a promising molecular moiety to improve targeting efficiency and drug accumulation in various cancer therapy.


Assuntos
Neoplasias Colorretais , Nanopartículas , Albuminas , Animais , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Ácidos Graxos , Xenoenxertos , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Neurosci Lett ; 698: 169-172, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30648614

RESUMO

Many studies have shown that saturated fat diet increases the risk of AD. Recently saturated very long chain fatty acids (VLCFAs) have been found be accumulated in AD patients. The variety of saturated fatty acids are found in the diets and human bodies. However, it is not clear which one or more fatty acids are involved in AD pathogenesis. This study investigated the effects of three saturated fatty acids with different carbon chain length (C16:0, C20:0, and C26:0) on amyloid precursor protein (APP) processing and amyloid-ß peptide (Aß) generation. Here, SH-SY5Y cells were treated with vehicle, C16:0, C20:0, and C26:0 (10 µmol/L, 24 h). Compared to the vehicle, C16:0 did not cause any significantly change in APP processing and Aß generation. C20:0 and C26:0 increased Aß levels and the expressions of APP, ß- and γ-secretase and decreased the expression of α-secretase, and C26:0 had the strongest effects among three fatty acids. Moreover, C20:0 and C26:0 significantly increased reactive oxygen species (ROS), and C16:0 had no such effect. These data indicate that saturated fatty acids with different carbon chain length (C16:0, C20:0 and C26:0) have different effects on the process of Aß generation, and fatty acids with longer chain (C20:0 and C26:0) have more potential to promote Aß production and an underlying mechanism of fatty acids action may be related to the elevated oxidative stress. This work supports saturated very long chain fatty acids may play a potential role in the pathogenesis of AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ácidos Graxos/metabolismo , Estresse Oxidativo/fisiologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Linhagem Celular , Humanos
15.
J Agric Food Chem ; 66(8): 1872-1880, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29429340

RESUMO

The effects of chain length and degree of unsaturation of fatty acids (FAs) on structure and in vitro digestibility of starch-protein-FA complexes were investigated in model systems. Studies with the rapid visco analyzer (RVA) showed that the formation of ternary complex resulted in higher viscosities than those of binary complex during the cooling and holding stages. The results of differential scanning calorimetry (DSC), Raman, and X-ray diffraction (XRD) showed that the structural differences for ternary complexes were much less than those for binary complexes. Starch-protein-FA complexes presented lower in vitro enzymatic digestibility compared with starch-FAs complexes. We conclude that shorter chain and lower unsaturation FAs favor the formation of ternary complexes but decrease the thermal stability of these complexes. FAs had a smaller effect on the ordered structures of ternary complexes than on those of binary complexes and little effect on enzymatic digestibility of both binary and ternary complexes.


Assuntos
Ácidos Graxos Insaturados/química , Proteínas de Plantas/química , Amido/química , Varredura Diferencial de Calorimetria , Digestão , Ácidos Graxos Insaturados/metabolismo , Estrutura Molecular , Proteínas de Plantas/metabolismo , Amido/metabolismo , Viscosidade , Difração de Raios X
16.
Front Microbiol ; 8: 123, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28203232

RESUMO

To get a better insight into the antimicrobial potency of short cationic lipopeptides, 35 new entities were synthesized using solid phase peptide strategy. All newly obtained lipopeptides were designed to be positively charged from +1 to +4. This was achieved by introducing basic amino acid - lysine - into the lipopeptide structure and had a hydrophobic fatty acid chain attached. Lipopeptides were subjected to microbiological tests using reference strains of Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Gram-positive bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Enterococcus faecalis, and fungi: Candida albicans, Candida tropicalis, Aspergillus brasiliensis. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimal fungicidal concentration (MFC) were established for each strain. The toxicity toward human cells was determined by hemolysis tests via minimum hemolytic concentration (MHC) determination. The effect of the trifluoroacetic acid (TFA) counter ion on the antimicrobial activity of lipopeptides was also examined by its removing and performing the antimicrobial tests using counter ion-free compounds. The study shows that lipopeptides are more potent against Gram-positive than Gram-negative strains. It was revealed that positive charge equals at least +2 is a necessary condition to observe significant antimicrobial activity, but only when it is balanced with a proper length of hydrophobic fatty acid chain. The hemolytic activity of lipopeptides strongly depends on amino acid composition of the hydrophilic portion of the molecule as well as fatty acid chain length. Compounds endowed with a greater positive charge were more toxic to human erythrocytes. This should be considered during new lipopeptide molecules design. Our studies also revealed the TFA counter ion has no significant effect on the antimicrobial behavior of cationic lipopeptides.

17.
Clin Biochem ; 49(16-17): 1283-1287, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27476911

RESUMO

OBJECTIVES: Fourier transform infrared (FTIR) spectroscopic determination of faecal fat is a simple and elegant alternative for the classical Van De Kamer approach. Besides quantification of the total amount of fat, analysis of the lipase hydrolysis efficiency (fatty acid/triglyceride ratio), fatty acid chain length and trans-unsaturated fatty acids could provide a better monitoring of dietary treatment. DESIGN AND METHODS: Stool samples (26 routine samples and 36 cystic fibrosis patients) were analysed with the Perkin Elmer Spectrum Two® spectrometer (3500-450cm-1). Fatty acid/triglyceride ratio was calculated using the absorbance ratio at 2855:1746cm-1. To estimate lipase hydrolysis efficiency, sample ratios were compared with the ratio of butter and pure free fatty acids. Mean fatty acid chain length was calculated using the absorbance ratio at 2855:1709cm-1. The absorbance at 966cm-1 was used to trace the presence of trans-type unsaturated fatty acids. RESULTS: Butter showed a low fatty acid/triglyceride ratio (1.21) and pure free fatty acids a high fatty acid/triglyceride ratio (6.76). Mean fatty acid/triglyceride ratio of routine stool samples was 4.16±1.01. The applicability of fatty acid/triglyceride ratios was also tested in cystic fibrosis patients under treatment with a mean of 4.92±0.98. Relative absorbance contribution per carbon atom was 0.06 (ratio 1.06 for C18 standard, 0.91 for C16 standard). The mean ratio of the stool samples was 1.12 (mean acyl chain length of C19), with values ranging from 0.73 (C12) to 1.68 (C28). The presence of traceable amounts of trans-unsaturated fatty acids was also demonstrated. CONCLUSIONS: For the analysis of faecal material, FTIR provides unique information, difficult to obtain using other techniques. These findings offer perspectives for diet monitoring in patients with (non-)pancreatic malabsorption.


Assuntos
Gorduras/análise , Fezes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Gorduras/classificação , Humanos
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