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1.
Food Chem ; 446: 138764, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38408399

RESUMO

Red clover (Trifolium pratense) isoflavone was supplemented to dairy cows, and antioxidant capacity of milk was assessed. Treated cows increased the activities of antioxidant enzymes, reduced production of oxidation products, and enhanced the concentrations of vitamin E and vitamin C. Moreover, milk fatty acid profile was positive influenced by 8 g/kg red clover isoflavone, with changes in the lower saturated and higher unsaturated fatty acids. We further demonstrated the efficacy of antioxidant capacity of milk in mice, found that milk from cows feeding red clover isoflavone increased the expressions of antioxidant enzymes, and alleviated lipopolysaccharide (LPS)-stimulated tissue damage of duodenum and jejunum, which was related to upregulated metabolism pathways of carbohydrate, lipid, and amino acid, as well as downregulated inflammatory related pathways. Together, dietary supplementation of red clover isoflavone is an effective way to improve milk antioxidant capacity, providing a natural strategy for developing functional foods.


Assuntos
Leite , Trifolium , Feminino , Bovinos , Animais , Camundongos , Leite/química , Trifolium/química , Antioxidantes/análise , Dieta/veterinária , Lactação , Silagem/análise , Suplementos Nutricionais , Ração Animal/análise
2.
Anim Nutr ; 16: 306-312, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38371476

RESUMO

This study was to conducted to investigate the effect of red clover isoflavones on the health indicated by immune status and blood biochemistry in dairy cows. Sixty-eight healthy Holstein lactating cows were randomly divided into four treatments (n = 17 per treatment) from 5 blocks according to milk yield using a randomized complete block design. No initial differences in parity (2.13 ± 1.21), days in milk (165 ± 21 d), and milk yield (33.93 ± 3.81 kg/d) between groups. Cows were fed the basal diet supplemented with 0, 2, 4, or 8 g/kg red clover extract (RCE) in diet (dry matter based). Feeding, refusal feed weights, and milk yield were recorded three consecutive days in weeks 0, 4, 8, and 12. Blood was collected from the tail vein of the cows on the last day of weeks 4, 8 and 12, 1 h after the morning feeding, and analyzed for hormones, immunoglobulins, inflammatory markers, and markers of liver and kidney activities. The dry matter intake was significantly decreased by 3.7% in the 8 g/kg group (P < 0.05). The fat-corrected milk yield was significantly higher in both of the 2 and 4 g/kg groups (P < 0.01). Plasma estradiol and prolactin showed a quadratic effect with increasing RCE levels, with the highest in the 4 g/kg group (P < 0.05). Plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß levels decreased linearly with increasing dietary RCE levels. Plasma IL-18 levels showed a quadratic effect with increasing dietary RCE levels, with significantly lower levels in both of the 2 and 4 g/kg groups (P < 0.05). Plasma immunoglobulin A and D-lactic acid levels showed a quadratic effect with increasing dietary RCE levels, with significantly higher level in the 4 g/kg group (P < 0.05). The liver function and kidney activity makers were similar (P > 0.05). These results recommend the supplementation of RCE at a level from 2 to 4 g/kg DM.

3.
Food Chem ; 442: 138369, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38232615

RESUMO

This study investigated the impact of magnetic nanoparticles (MNPs) -assisted cryogenic freezing integrated with MNPs combined microwave thawing (NNMT) on the structural integrity of myofibrillar proteins and alterations in protein profiles in salmon fillets. The NNMT showed the lowest myofibrillar fragmentation index (MFI) value (2.73 ± 0.31) among the four freezing-thawing groups. The myofibrillar structure exhibited the highest level of integrity, while the myofibrillar proteins demonstrated minimal aggregation and displayed the most stable secondary and tertiary structures in response to NNMT treatment. Compared with the other three treatments, NNMT exhibited a high abundance of ionic and hydrogen bonds, resulting in stronger interactions between the proteins and water molecules. The label-free proteomics analysis revealed that different freezing-thawing methods primarily affected the cytoskeletal proteins, with collagen and myosin being down-regulated due to degradation caused by cold stress and recrystallization. Additionally, NNMT demonstrated a superior capability in stabilizing salmon cytoskeletal proteins.


Assuntos
Salmo salar , Animais , Congelamento , Proteômica , Proteínas , Miosinas
5.
Food Funct ; 14(3): 1510-1519, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36651848

RESUMO

Umami peptides have currently become the research focus in the food umami science field and the key direction for umami agent development. This is because umami peptides have good processing characteristics, umami and nutritional values. We here used virtual screening (including online enzymolysis through ExPASy PeptideCutter, bioactivity screening using the PeptideRanker, toxicity and physicochemical property prediction using Innovagen and ToxinPred software), molecular docking, and electronic tongue analysis to identify umami peptides generated from Atlantic cod myosin. Twenty-three putative umami peptides were screened from the myosin. Molecular docking results suggested that these 23 peptides could enter the binding pocket in the T1R3 cavity, wherein Glu128 and Asp196 were the main amino acid residues, and that hydrogen bonding and electrostatic interactions were the main binding forces. Twelve synthetic peptides tested on the electronic tongue exhibited umami taste and a synergistic effect with monosodium glutamate (MSG). Among them, GGR, AGCD, and SGDAW had higher umami intensities than the other peptides, while SGDAW and NDDGW exhibited stronger umami-enhancing capabilities in 0.1% MSG solution. This study offers a method for the rapid screening of umami peptides from marine protein resources and places the foundation for their application in the food industry.


Assuntos
Gadus morhua , Animais , Simulação de Acoplamento Molecular , Gadus morhua/metabolismo , Glutamato de Sódio/química , Peptídeos/química , Paladar , Receptores Acoplados a Proteínas G/metabolismo
6.
Ultrason Sonochem ; 93: 106299, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36652814

RESUMO

To study the physicochemical properties of micro-nanoparticles (MNPs) in thermoultrasonic treated fishbone soup, it was subjected to ultra-filtration with a 100 kDa ultrafiltration membrane to obtain large MNPs (LMNPs) and small MNPs (SMNPs). LMNPs and SMNPs were treated with force-breakers, and the interactions of the MNPs with five characteristic volatile compounds were investigated. LMNPs covered most proteins (222.66 mg/mL) and fatty acids (363.76 mg/g), while SMNPs was mostly soluble small molecules with taste substances like total free amino acids (85.26 mg/g), organic acids (2.55 mg/mL), and 5'-nucleotides (169.17 mg/100 mL). The stability of LMNPs is significantly higher than raw bone soup, and SMNPs can exist stably in the solution. Correlation analysis between flavor substance content and flavor suggested that the overall flavor profile of halibut bone soup was closely related to the content changes of 72 significant influence variables. The binding of LMNPs to characteristic flavor compounds was largely affected by hydrophobic interactions, hydrogen bonds, and ionic effects. While the binding of SMNPs to characteristic flavor compounds was largely determined by hydrophobic interaction and hydrogen bonding. This study explores the characteristics of MNPs and provides the possibility to clarify the interaction mechanism between MNPs and flavor.


Assuntos
Nanopartículas , Paladar , Odorantes/análise , Alimentos Marinhos/análise , Aminoácidos/análise
7.
Crit Rev Food Sci Nutr ; : 1-13, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36102134

RESUMO

Color is an essential criterion for assessing the freshness, quality, and acceptability of red meat and certain fish with red muscle. Myoglobin (Mb), one of the significant pigment substances, is the uppermost reason to keep the color of red meat. Their oxidation and browning are easy to occur throughout the storage and processing period. Natural antioxidants are substances with antioxidant activity extracted from plants, such as plant polyphenols. Consumers prefer natural antioxidants due to safety concerns and limitations on the use of synthetic antioxidants. In recent years, plant polyphenols have been widely used as antioxidants to slow down the deterioration of product quality due to oxidation. As natural antioxidants, it is necessary to strengthen the researches on the antioxidant mechanism of plant polyphenols to solve the discoloration of red meat and certain fish. A fundamental review of the relationship between Mb oxidation and color stability is discussed. The inhibiting mechanisms of polyphenols on lipid and Mb oxidation are presented and investigated. Meanwhile, this review comprehensively outlines applications of plant polyphenols in improving color stability. This will provide reference and theoretical support for the rational application of plant polyphenols in green meat processing.

8.
Yonsei Med J ; 63(3): 220-228, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35184424

RESUMO

PURPOSE: In this article, we aimed to investigate the influences of luteolin on inflammatory injury to cardiomyocytes induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: H9c2 cells were pretreated with different concentrations of luteolin (10, 20, and 50 µM) for 12 h and then stimulated with 10 µg/mL LPS or no LPS for 6 h. Cell viability was detected by CCK-8 assay. Cell apoptosis was determined by flow cytometry. QRT-PCR and Western blotting were utilized to examine mRNA and protein levels. ELISA was used to determine the levels of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin (IL)-6, IL-1ß, and IL-18 in cell supernatants among different groups of H9c2 cells. Immunofluorescence was applied to evaluate reactive oxygen species formation in H9c2 cells. M-mode images of echocardiography, the ejection fraction test, fractional shortening test, end-systolic volume test, and end-diastolic volume test of mouse heart function were obtained by ultrasonic electrocardiogram. RESULTS: Luteolin could alleviate inflammatory damage and inflammatory factor expression among LPS-induced H9c2 cells. Additionally, we found that luteolin decreased LPS-stimulated inflammatory damage in H9c2 cells by down-regulating NOD-like receptor family pyrin domain containing 3 (Nlrp3). Luteolin also improved myocardial function in mice treated with LPS and reduced myocardial relaxation. Luteolin reversed myocardial histological abnormalities in mice and reduced inflammation and cardiomyocyte apoptosis. Additionally, luteolin inhibited oxidative stress-mediated myocardial and systemic tissue damage in mice. Finally, luteolin reduced LPS-induced inflammatory damage in mouse cardiomyocytes by down-regulating Nlrp3. CONCLUSION: We found that luteolin could reduce inflammatory damage to cardiomyocytes induced by LPS by down-regulating Nlrp3.


Assuntos
Lipopolissacarídeos , Miócitos Cardíacos , Animais , Apoptose , Lipopolissacarídeos/toxicidade , Luteolina/metabolismo , Luteolina/farmacologia , Camundongos , Miócitos Cardíacos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
9.
J Healthc Eng ; 2022: 4012304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35132357

RESUMO

OBJECTIVE: To explore the application value of perioperative nursing for patients with brain tumors with epilepsy symptoms under the cortical electrocorticography (EEG) monitoring. METHODS: A total of 86 patients with brain tumor complicated with epilepsy admitted to the department of brain surgery of our hospital from January 2018 to December 2019 were selected as the research objects, and all underwent resection under cortical EEG monitoring. According to different nursing methods, they were divided into the control group and observation group, each with 43 cases. The control group was given perioperative basic nursing, and the observation group was given perioperative comprehensive nursing. The EEG image of the patient during the operation was observed by a portable EEG monitor. Anxiety and depression were assessed by self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores. The self-made satisfaction questionnaire was used to investigate the nursing satisfaction. A visual analogue (VAS) score is used to assess pain degree. A multiparameter monitor was used to detect the patient's heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The quality of life was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-30). The complication rate and recurrence rate were also counted. RESULTS: Eighty-six patients with epileptic brain tumor developed spikes in 35 cases, including 7 meningiomas, 22 gliomas, and 6 cholesteatomas; 27 cases of sharp waves, including 14 meningiomas, 12 gliomas, and 1 case of cholesteatomas; and 24 cases of complex wave, including 9 cases of meningioma, 13 cases of glioma, and 2 cases of cholesteatoma. There was no significant difference in the scores of SAS, SDS, VAS, HR, SBP, DBP, and quality of life between the two groups at T0. The VAS score increased at T1 and T2, and the increase in the control group was greater than that in the observation group. At T3 and T4, the SAS, SDS, and VAS scores of the two groups decreased, and the observation group decreased more than the control group. HR, SBP, and DBP of the two groups showed an upward trend at T1 and T2, and the increase in the control group was more significant than that in the observation group. At T3, the three indicators of the two groups decreased, and the observation group decreased more significantly than the control group. At T4, the scores of all indicators of the quality of life of the two groups increased, and the observation group increased more significantly than the control group. The nursing satisfaction of the observation group was higher than that of the control group. The complication rate and recurrence rate in the observation group were decreased compared with the control group. CONCLUSION: Perioperative comprehensive nursing intervention for patients with epileptic brain tumor undergoing resection under cortical EEG monitoring can reduce or even eliminate the recurrence rate of epilepsy, reduce the patient's pain and stress response, and improve the patient's quality of life. It can also reduce the occurrence of complications, improve nursing satisfaction, thereby improving patient compliance, and has a high clinical application value.


Assuntos
Neoplasias Encefálicas , Colesteatoma , Epilepsia , Glioma , Neoplasias Meníngeas , Meningioma , Encéfalo , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Eletrocorticografia , Epilepsia/cirurgia , Glioma/complicações , Glioma/cirurgia , Humanos , Dor , Enfermagem Perioperatória , Qualidade de Vida
10.
J Food Sci ; 87(1): 216-230, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34841524

RESUMO

In this study, halibut bone, a byproduct of Greenland halibut processing, was prepared into a thick soup through a non-frying process. The formation of colloidal micro-nano particles and flavor characteristics in halibut bone soup was explored. The results showed that the nutrients in halibut bones migrated to the soup continuously with the cooking process and reached the highest concentration (total sugars, 38.16 mg/100 ml; water-soluble proteins, 25.71 mg/ml; fatty acids, 2.15 g/100 ml; solids, 1.14 g/100 ml) at 150 min. Taste substances such as organic acids, 5'-nucleotides and total free amino acids (TFAAs) content in halibut bone soup also reached maximum at 150 min. At this time, results for particle size showed that MNPs with uniform size (725.62 nm) were formed, which made the bone soup milky white, stable, and had good tasting. Headspace-gas chromatography-ion mobility spectrometry results showed that a total of 59 volatile substances were detected from the halibut bone soup. The content of volatile flavor substances in the 150 min group was lower than that in the 90-120 min group. Meanwhile, aldehydes and ketones gradually became esters. PRACTICAL APPLICATION: Soup is an indispensable part of the world food culture. In order to increase the added value of Greenland halibut, halibut bone soup was studied in this paper. This study found that halibut bone soup that had not been fried, formed the MNPs and has a more harmonious and pleasant flavor. Thus, non-fried halibut bone soup is a good processing method and can improve economic efficiency.


Assuntos
Linguado , Compostos Orgânicos Voláteis , Animais , Aromatizantes , Cromatografia Gasosa-Espectrometria de Massas , Groenlândia , Paladar , Compostos Orgânicos Voláteis/análise
11.
J Sci Food Agric ; 102(8): 3150-3159, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34791675

RESUMO

BACKGROUND: Antioxidant activity has been found in fermented fish sauce. In this experiment, the properties of endogenous protease and antioxidant activity were studied in anchovy sauce during fermentation. The correlation between protease activity and antioxidant activity in fermented anchovy sauce was analyzed using the partial least squares (PLS) method. RESULTS: The results showed that at least four proteases were present in the endogenous enzyme solution, and the optimum pH values were 2.5, 5.5, 9.0, and 12.5, respectively. The maximum inhibition rate of endogenous protease, from high to low, was: serine protease inhibitor > trypsin inhibitor > aspartic protease inhibitor (pepsin inhibitor) > cysteine protease inhibitor > metalloprotease inhibitor. At the sixth month of fermentation, fish sauce had stronger trypsin, pepsin-like activity, and antioxidant activity. At the ninth month of fermentation, the cathepsin activity was greater. A model correlating changes in protease activity with antioxidant activity suggested that the trypsin and serine protease were the main factors affecting antioxidant activity. CONCLUSION: This study reports a model correlating changes in protease activity with the antioxidant activity of fish sauce. It lays a foundation for further exploration of the formation of antioxidant substances and antioxidant effects during the process of fish sauce fermentation. © 2021 Society of Chemical Industry.


Assuntos
Antioxidantes , Produtos Pesqueiros , Animais , Fermentação , Produtos Pesqueiros/análise , Peixes , Pepsina A , Peptídeo Hidrolases , Tripsina
12.
Ultrason Sonochem ; 79: 105785, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34653917

RESUMO

In order to investigate the effects of thermoultrasonic treatment (TUT) on the formation of colloidal micro-nano particles (MNPs) and the quality of halibut bone soup, nutrients, particle characteristics, and flavor characteristics were analyzed. The morphology of MNPs was studied using an optical microscope. Results showed that TUT could increase the nutrient content (total sugars, 22.15 mg/100 mL; water soluble proteins, 173.24 mg/mL; fatty acids, 1779.7 mg/100 mL; solids, 3.16 g/100 mL), reduce the particle size (605.92 nm) and interfacial tension. Meanwhile, TUT make the halibut bone soup has better emulsifying characteristics and stability. The contents of flavor substances, such as esters, 5'-nucleotides, organic acids in the halibut bone soup were more abundant, while the contents of hexanal and 1-octen-3-ol and fishy off-flavor were reduced in TUT group. The overall odor and taste outline were more harmonious. Therefore, TUT can be used in the production of high quality fish bone soup, and TUT could be considered as a good deep processing technology for halibut bone and improve economic efficiency.


Assuntos
Linguado , Animais , Aromatizantes , Groenlândia , Odorantes/análise , Paladar , Ultrassom , Compostos Orgânicos Voláteis
13.
Food Funct ; 12(11): 5027-5037, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33955998

RESUMO

Fish sauce has a prominent umami flavor. In this study, umami peptides were isolated, purified and identified from Thai fish sauce, and their structure-activity relationships were analyzed. Six novel umami peptides were characterized and verified by using sensory evaluation and a electronic tongue. Molecular docking with T1R1/T1R3 receptors showed that the interaction forces were mainly hydrogen bonds, electrostatic interaction and van der Waals force. In the constructed three dimensional quantitative structure-activity relationship model (3D-QSAR) model, the regression coefficient (R2) for the degree of dispersion between the predicted molecular and the experimental values of the six peptides was 0.976. The association between the structure and activity of umami peptides was revealed through 3D-QSAR. Results showed that the spatial effect was significant for long chain peptides.


Assuntos
Produtos Pesqueiros/análise , Peixes , Peptídeos/química , Animais , Aromatizantes , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-Atividade , Paladar , Tailândia
14.
J Sci Food Agric ; 101(8): 3140-3155, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33185275

RESUMO

BACKGROUND: Fish sauce has a subtle flavor with prominent umami and salty taste, and is accompanied by a certain sweetness and bitterness. In order to identify a wider range of umami peptides, Chinese southern and northern anchovy sauce were selected for the study. RESULTS: Seventeen peptides were obtained by separation and purification, and their taste activity was predicted. Through the taste characterization and descriptive analysis, it was found that the synthesized peptides were umami and umami-enhancing peptides. Seventeen umami peptides were simulated and embedded into the umami receptor T1R1/T1R3 by inserting into the Venus flytrap domain (VFTD) of the T1R3 subunit; the interaction forces were mainly hydrogen bonding, electrostatic interaction, van der Waals force and hydrophobic interaction. According to the docking interaction energies, long-chain peptides may be easier to bind to the receptor than short-chain peptides. Asp196, Glu128 and Glu197 were the main binding sites for docking, and could affect umami synergism. CONCLUSION: For the first time, novel umami peptides in Chinese anchovy sauce have been reported. This study is helpful for discovering umami marine resource peptides, and can provide a basis for further understanding the flavor system of anchovy sauce. © 2020 Society of Chemical Industry.


Assuntos
Produtos Pesqueiros/análise , Aromatizantes/química , Peptídeos/química , Animais , Sítios de Ligação , China , Peixes , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Ligação Proteica , Domínios Proteicos , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Paladar
15.
Nanomaterials (Basel) ; 10(5)2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32429472

RESUMO

Regular chemotherapy cannot eliminate leukemic cells, due to the sparse distribution of cancer cells in leukemia patients. Here, we report a precise nanostructure of folate-overhung mitoxantrone DNA tetrahedron that enables the treatment of leukemic cells by targeted action. Folate is used as a targeting molecule and synthesized with DNA strand in forming the folate-overhang DNA complement, and the complement is then separately base-paired onto six sides of the fabricated DNA tetrahedron. Mitoxantrone is used as an anticancer agent and intercalated into the double strands of the folate-overhung DNA tetrahedron for drug loading. The evaluation studies are performed on leukemia BALL-1 and K562 cells. The results demonstrate that the folate-overhung mitoxantrone DNA tetrahedra (approximately 25 nm) are able to target leukemic cells, transport across the nuclei membrane, induce the apoptosis, and enhance the overall efficacy of treating leukemic cells in vitro and in leukemia-bearing mice. This study provides a potential drug-containing DNA nanostructure, to clean the sparsely distributed leukemic cells in patients.

16.
RSC Adv ; 8(20): 10806-10817, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35541536

RESUMO

Polymer materials with electrically conductive properties have good applications in their respective fields because of their special properties. However, they usually exhibited poor mechanical properties and biocompatibility. In this work, we present a simple approach to prepare conductive sodium alginate (SA) and carboxymethyl chitosan (CMCS) polymer hydrogels (SA/CMCS/PPy) that can provide sufficient help for peripheral nerve regeneration. SA/CMCS hydrogel was cross-linked by calcium ions provided by the sustained release system consisting of d-glucono-δ-lactone (GDL) and superfine calcium carbonate (CaCO3), and the conductivity of the hydrogel was provided by doped with polypyrrole (PPy). Gelation time, swelling ratio, porosity and Young's modulus of the conductive SA/CMCS/PPy hydrogel were adjusted by polypyrrole content, and the conductivity of it was within 2.41 × 10-5 to 8.03 × 10-3 S cm-1. The advantages of conductive hydrogels in cell growth were verified by controlling electrical stimulation of cell experiments, and the hydrogels were also used as a filling material for the nerve conduit in animal experiments. The SA/CMCS/PPy conductive hydrogel showed good biocompatibility and repair features as a bioactive biomaterial, we expect this conductive hydrogel will have a good potential in the neural tissue engineering.

17.
Mol Med Rep ; 17(1): 1083-1092, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115488

RESUMO

General anesthesia is widely used in pediatric surgery, although the influence of general anesthesia on cerebellar information transmission and motor function is unclear. In the present study, neonatal mice received repeated inhalation of sevoflurane, and electrophysiological alterations in Purkinje cells (PCs) and the development of motor functions were detected. In addition, γ­aminobutyric acidA receptor ε (GABAA­R ε) subunit knockout mice were used to investigate the mechanism of action of sevoflurane on cerebellar function. In the neonatal mice, the field potential response of PCs induced by sensory stimulation and the motor function indices were markedly inhibited by sevoflurane, and the inhibitory effect was positively associated with the number of repetitions of anesthesia. In additional the GABAA­R ε subunit level of PCs was promoted by sevoflurane in a dose­dependent manner, and the inhibitory effects of sevoflurane on PC field potential response and motor function were alleviated in GABAA­R ε subunit knockout mice. The GABAA­R ε subunit was activated by sevoflurane, leading to inhibition of sensory information transmission in the cerebellar cortex, field potential responses of PCs and the development of cerebellar motor function. The present study provided experimental evidence for the safe usage of sevoflurane in clinical anesthesia, and suggested that GABAA­R ε subunit antagonists may be considered for combined application with general anesthesia with repeated inhalation of sevoflurane, for adverse effect prevention in the clinic.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Éteres Metílicos/administração & dosagem , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/fisiologia , Receptores de GABA-A/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Comportamento Animal , Córtex Cerebelar/efeitos dos fármacos , Córtex Cerebelar/fisiologia , Feminino , Locomoção/efeitos dos fármacos , Camundongos , Camundongos Knockout , Receptores de GABA-A/genética , Sevoflurano
18.
Sci Rep ; 7(1): 3487, 2017 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-28615716

RESUMO

Surgery and radiotherapy cannot fully remove brain glioma; thus, chemotherapy continues to play an important role in treatment of this illness. However, because of the restriction of the blood-brain barrier (BBB) and the regeneration of glioma stem cells, post-chemotherapy relapse usually occurs. Here, we report a potential solution to these issues that involves a type of novel multifunctional vinblastine liposomes equipped with transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8. Studies were performed on brain glioma and glioma stem cells in vitro and were verified in brain glioma-bearing mice. The liposomes were transported across the BBB, killing brain glioma and glioma stem cells via the induction of necrosis, apoptosis and autophagy. Furthermore, we reveal the molecular mechanisms for treating brain glioma and glioma stem cells via functionalized drug lipid vesicles.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Lipossomos/administração & dosagem , Células-Tronco Neoplásicas/efeitos dos fármacos , Vimblastina/administração & dosagem , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Lipossomos/química , Camundongos , Oligopeptídeos/química , Receptores da Transferrina/química
19.
Int J Nanomedicine ; 12: 4163-4176, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28615943

RESUMO

Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice. Mechanistic studies revealed that the liposomes could target the mitochondria, activate the apoptotic enzymes caspase 8, 9, and 3, upregulate the proapoptotic protein Bax while downregulating the antiapoptotic protein Mcl-1, and induce the generation of reactive oxygen species (ROS) through an apoptosis cascade. In xenografted mice bearing breast cancer, the epirubicin liposomes demonstrated prolonged blood circulation, significantly increased accumulation in tumor tissue, and robust anticancer efficacy. This study demonstrated that functional epirubicin liposomes could significantly induce programmed death of refractory breast cancer by activating caspases and ROS-related apoptotic signaling pathways, in addition to the direct killing effect of the anticancer drug itself. Thus, we present a simple nanomedicine strategy to treat refractory breast cancer.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Epirubicina/farmacologia , Lipossomos/química , Lipossomos/farmacologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Caspases/metabolismo , Epirubicina/administração & dosagem , Feminino , Humanos , Lipossomos/administração & dosagem , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Oncotarget ; 8(25): 40906-40921, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28402948

RESUMO

Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo. The results showed that the CNP-modified vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the brain glioma, and destroy neovasculatures effectively. The above mechanisms could be associated with the following aspects, namely, long circulation in the blood; drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated transcytosis; elimination of brain glioma cells and disruption of neovasculatures by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid vesicles could induce apoptosis of the glioma cells. The mechanisms could be related to the activations of caspase 8, caspase 3, p53, and reactive oxygen species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles could be used as a carrier material for treating brain glioma and disabling glioma neovasculatures.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Lipídeos/administração & dosagem , Peptídeo Natriurético Tipo C/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Glioma/patologia , Humanos , Lipídeos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Peptídeo Natriurético Tipo C/química , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vimblastina/química , Vinorelbina
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