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1.
Hear Res ; 396: 108055, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32814237

RESUMO

Inner ear hair cells are mechanosensitive cells responsible for sensing and transmitting signals to the brain to be interpreted as sound or head position/movement. The zinc-finger protein, gfi1, is expressed in differentiating neurons and inner ear hair cells. Gfi1 deficiency leads to a massive loss of cochlear hair cells in mice. However, the mechanism remains unclear. To develop an effective molecular therapy for hearing loss, it is critical to first understand the relationship between gfi1 and hair cell development. We demonstrated in the zebrafish model that gfi1.2 was initially expressed in the inner ear at 14 h post-fertilization (hpf), preceding the expression of gfi1.1 at 19 hpf. In the morpholino-mediated gfi1.2 knockdown mutants, hair cells reduced in number without altering the expression of pax2a, dlx3b, atho1a and pou4f3, the markers for otic patterning and specification. There was a down-regulation of the pro-neuronal genes, ngn1 and atoh1b in the context of gfi1.2 knockdown, which was rescued by the exogenous gfi1.2. We also found that gfi1.2 may regulate ngn1 expression by suppressing id2a. Our results suggested that knockdown of gfi1.2 may lead to deafness through promoting cells proliferation in the pro-sensory region and interrupting cell differentiation.

2.
Mol Psychiatry ; 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681097

RESUMO

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

3.
Transl Psychiatry ; 10(1): 230, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32661266

RESUMO

Alzheimer's disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aß) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aß burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aß generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.

4.
Ying Yong Sheng Tai Xue Bao ; 31(4): 1063-1072, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32530179

RESUMO

We investigated the fire resistance conferred by different forest age groups (young, middle-age and mature forest) and organs (leaf, branch, and bark) of six typical tree species (Myrica rubra, Schima superba, Symplocos sumuntia, Machilus pingii, Castanopsis eyrei, and Quercus glauca) in Qingshigang national forest farm, Yanling County, Hunan Province, subtropical China. We measured morphological, physical, and chemical properties that could be used as proxies for fire resistance and examined the variances of fire resistance among different organs and age groups in the same tree species. Further, we comprehensively ranked all the tree species by their capacity in fire resistance. We found considerable variation in fire resistance among organs and age groups. Compared with branches and barks, leaves had relatively higher water content (53.7%), higher crude ash content (4.5%), and lower crude fiber content (23.9%). Fire resistance of trees decreased first and then increased with increasing stand age. Trees in middle-aged stage showed the lowest contents of water, crude ash, and crude fiber. The comprehensive scores of fire resistance for diffe-rent organs were significantly different among species. Fire resistance of leaves generally decreased in the order of M. pingii > C. eyrei > S. sumuntia > M. rubra > S. superba > Q. glauca. For branches, M. pingii and C. eyrei showed the strongest fire resistance, followed by M. rubra and S. superba. For barks, S. superba and C. eyrei were relatively stronger in fire resistance than other species, while M. pingii and Q. glauca were the weakest. The comprehensive scores of fire resistance performance of species were different. S. superba (1.033) and M. rubra (0.526) were the most fire-resistant species, while M. pingii (-0.405) and Q. glauca (-1.151) were the least fire-resistant. Therefore, S. superba and M. rubra were the preferred tree species for fire prevention forest belt in forests of subtropical southern China.


Assuntos
Fogo , Theaceae , China , Florestas , Árvores
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 239: 118511, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32480275

RESUMO

Phenol, o-cresol, p-cresol, catechol and resorcinol are five phenolic compounds with extremely similar structure. Their fluorescence spectra are hard to be analyzed because of the serious spectral overlaps between any two of the five phenolic components in the mixture system. In this experiment, multi-dimensional partial least-squares (N-PLS), unfolded partial least-squares (U-PLS) with residual bilinearization (RBL) and parallel factor analysis (PARAFAC) are employed to analyze the three-way fluorescence spectra aiming to achieve quantitative results. Meanwhile, a contrast of these three methods is given. The experiment results show that N-PLS/RBL and U-PLS/RBL algorithms are superior to PARARFAC in terms of analysis of highly overlapping three-way fluorescence spectra for concentration determination.

6.
Org Lett ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32589432

RESUMO

A general γ-C(sp2)-H iodination method directed by an aliphatic keto group has been developed under transition-metal-free conditions for the first time, generating iodoarenes in good to excellent yields with excellent site selectivity. This protocol features a wide range of aryl-substituted ketones, short reaction times, mild reaction conditions, and scalable synthetic procedures. A possible reaction mechanism was also proposed based on several control experiments.

7.
Autophagy ; : 1-22, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32432943

RESUMO

SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. Furthermore, we determined that SQSTM1 captured SCAP after its exit from the ER. The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. We termed this novel protein degradation pathway as the SQSTM1-mediated autophagy-independent lysosomal degradation (SMAILD) pathway. In vivo, lycorine ameliorates high-fat diet-induced hyperlipidemia, hepatic steatosis, and insulin resistance in mice. Our study demonstrated that the inhibition of SCAP through the SMAILD pathway could be employed as a useful therapeutic strategy for treating metabolic diseases. ABBREVIATION: 25-OHD: 25-hydroxyvitamin D; 3-MA: 3-methyladenine; ABCG5: ATP binding cassette subfamily G member 5; ABCG8: ATP binding cassette subfamily G member 8; ACACA: acetyl-CoA carboxylase alpha; AEBSF: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; AHI: anhydroicaritin; AKT/protein kinase B: AKT serine/threonine kinase; APOE: apolipoprotein E; ATF6: activating transcription factor 6; ATG: autophagy-related; BAT: brown adipose tissue; CD274/PD-L1: CD274 molecule; CETSA: cellular thermal shift assay; CMA: chaperone-mediated autophagy; COPII: cytoplasmic coat protein complex-II; CQ: chloroquine; DDIT3/CHOP: DNA damage inducible transcript 3; DNL: de novo lipogenesis; EE: energy expenditure; EGFR: epithelial growth factor receptor; eMI: endosomal microautophagy; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FADS2: fatty acid desaturase 2; FASN: fatty acid synthase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvate transaminase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS1: 3-hydroxy-3-methylglutaryl-CoA synthase 1; HSP90B1/GRP94: heat shock protein 90 beta family member 1; HSPA5/GRP78: heat hock protein family A (Hsp70) member 5; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INSIG1: insulin induced gene 1; LAMP2A: lysosomal associated membrane protein 2A; LDLR: low density lipoprotein receptor; LyTACs: lysosome targeting chimeras; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MBTPS1: membrane bound transcription factor peptidase, site 1; MEF: mouse embryonic fibroblast; MST: microscale thermophoresis; MTOR: mechanistic target of rapamycin kinase; MVK: mevalonate kinase; PROTAC: proteolysis targeting chimera; RQ: respiratory quotient; SCAP: SREBF chaperone; SCD1: stearoyl-coenzemy A desaturase 1; SMAILD: sequestosome 1 mediated autophagy-independent lysosomal degradation; SQSTM1: sequestosome 1; SREBF: sterol regulatory element binding transcription factor; TNFRSF10B/DR5: TNF receptor superfamily member 10b; TRAF6: TNF receptor associated factor 6; UPR: unfolded protein response; WAT: white adipose tissue; XBP1: X-box binding protein 1.

8.
J Stroke Cerebrovasc Dis ; 29(7): 104866, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32404283

RESUMO

OBJECTIVE: Post-stroke paralysis is a common contributor to deep vein thrombosis (DVT) of the lower extremities, but little is known about its epidemiology and anatomy. This prospective study aimed to investigate the clinical incidence and anatomical distribution of lower-extremity DVT in acute stroke. PATIENTS AND METHODS: A total of 679 patients diagnosed with acute stroke (ischemic stroke, n = 507; hemorrhagic stroke, n = 172) were enrolled. Lower-extremity DVT was evaluated using vascular ultrasonography, and classified into three subtypes: central type, peripheral type and mixed type. Then, the incidence and anatomical distribution of DVT were analyzed. RESULTS: For patients with ischemic stroke, a total of 107 patients (21.1%) were affected by DVT, and 119 extremities were found with DVT, which included 114 extremities with peripheral-type DVT and five extremities with mixed-type DVT. For patients with hemorrhagic stroke, a total of 49 patients (28.5%) were affected by DVT, and 55 extremities were found with DVT, which included 51 extremities with peripheral-type DVT and four extremities with mixed-type DVT. The incidence of DVT was significantly higher in patients with hemorrhagic stroke than in patients with ischemic stroke (P < 0.05). Intermuscular veins were the most commonly affected (96.6%), followed by peroneal veins (15.5%), posterior tibial veins (9.2%), popliteal veins (4.0%), and femoral veins (4.0%). There was no significant difference in the anatomical distribution of DVT between ischemic and hemorrhagic stroke (P > 0.05). CONCLUSION: DVT is a common complication of acute stroke, and hemorrhagic stroke is associated with a higher incidence of DVT. The anatomical distribution of DVT revealed no heterogeneity between ischemic and hemorrhagic stroke, and isolated DVT in intermuscular veins were the most common.


Assuntos
Isquemia Encefálica/epidemiologia , Hemorragias Intracranianas/epidemiologia , Extremidade Inferior/irrigação sanguínea , Acidente Vascular Cerebral/epidemiologia , Ultrassonografia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , China/epidemiologia , Feminino , Humanos , Incidência , Hemorragias Intracranianas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem
9.
Mater Sci Eng C Mater Biol Appl ; 109: 110563, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228984

RESUMO

Stem cells from human exfoliated deciduous teeth (SHED) are considered the best current source of human stem cells due to their ability to differentiate into multiple cell lineages. Dynamic co-culture systems can improve the culture environment, as they provide cells with signaling factors, extracellular matrixes, and cellular shear force, as well as enable the formation of heterotypic clusters. We seeded SHED in 3D silk fibroin porous scaffolds under static and dynamic cultures for 28 days, using the NIH3T3 cultivated medium as an induction agent. Many hepatospheres formed in these porous scaffolds, and cellular viability was shown to continually increase by MTT assays. Hepatic AFP and ALB gene expression, as well as glycogen storage, albumin secretion, and urea synthesis, were greater in cells in the 3D porous scaffold under a dynamic culture than in those cultured under 3D static culture and petri dish conditions. However, the 3D static culture is still superior to the traditional petri dish culture. The NIH3T3 cultivated medium can significantly induce hepatic differentiation of SHED, while the 3D dynamic culture system significantly enhances hepatic differentiation of SHED. This study provides alternative sources of hepatocytes for liver disease treatment.

10.
Clin Transplant ; 34(3): e13810, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011059

RESUMO

This retrospective multicenter cohort study aimed to compare the outcome of haploidentical hematopoietic stem cell transplantation (HID-HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anemia (SAA) patients 40 years of age and older. With a median follow-up time of 17.6 months, 85 consecutive patients were enrolled in the study, and the median patient age was 45 years (40, 58). The cumulative engraftment rates of neutrophil and platelet were 98.8 ± 0.0% and 92.9 ± 0.1%. The cumulative incidences of Grade 2-4 acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) at 3 years were 14.1 ± 0.1% and 17.3 ± 0.2%. The 3-year estimated overall survival (OS) and failure-free survival (FFS) were 91.2 ± 3.2% and 89.7 ± 3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG score ≥2. HID-HSCT was associated with a higher incidence of GvHD, but the difference of 3-year estimated OS between HID group and the other two cohorts was not significant (86.7 ± 6.4% for HID vs 92.1% ± 4.4% for MSD and 100% for URD, P = .481). HID-HSCT might be a feasible alternative option for selected SAA patients aged 40 years and older without a matched donor.

11.
Mol Med Rep ; 21(2): 842-850, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974627

RESUMO

The present study investigated the role of cytochrome P450 family 2 subfamily E polypeptide 1 (CYP2E1) in the development and progression of gastric cancer (GC). The expression levels of CYP2E1 in MGC­803 GC cells and normal GES­1 cells were investigated via western blotting, and it was identified that the expression of CYP2E1 was different between GES­1 and MGC­803 cells. CYP2E1 was overexpressed in MGC­803 cells using a lentiviral vector GV358. Cell Counting Kit­8, flow cytometry, cell migration and Matrigel invasion assays suggested that overexpression of CYP2E1 promoted the proliferation and invasion, and inhibited the apoptosis of GC cells. The relationship between CYP2E1 expression and key signaling molecules in the PI3K/Akt/mTOR signaling pathway was assessed. Reverse transcription­quantitative PCR analysis showed that mTOR mRNA expression was significantly increased after overexpression of CYP2E1 (P<0.05). Western blotting results showed that overexpression of CYP2E1 upregulated the expression of phosphorylated (p)­Akt, p­mTOR and p­p70 ribosomal protein S6 kinase (P70S6K; Ser371) proteins (P<0.05). To further investigate the relationship between CYP2E1 and the PI3K/Akt/mTOR signaling pathway in GC cells, MGC­803 cells were treated with the PI3K inhibitor LY294002, and changes in the expression levels of PI3K, AKT, mTOR, P70S6K and CYP2E1 were observed. The present results showed that LY294002 downregulated the expression of PI3K, CYP2E1, AKT, mTOR and P70S6K (P<0.05). Therefore, changes in the biological function of GC cells induced by CYP2E1 overexpression may be via the PI3K/Akt/mTOR signaling pathway.


Assuntos
Citocromo P-450 CYP2E1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias Gástricas/enzimologia , Serina-Treonina Quinases TOR/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Citocromo P-450 CYP2E1/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Lentivirus/metabolismo , Invasividade Neoplásica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
12.
Food Chem ; 307: 125546, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639580

RESUMO

Zearalenone (ZEN) is one of the most widely distributed harmful mycotoxins produced by Fusarium species, especially deposited in corn oil. In this study, we systematically tracked the changes of ZEN in the refining of corn oil, and especially during neutralization process. An alkali neutralization process could remove certain amounts of ZEN that was much more than that of others refining steps. In a mimicking condition, ZEN contents decreased continuously and significantly with increasing neutralization temperature. However, when returned to neutral, recoverable ZEN decreased with increasing temperature, which confirmed more degradation of ZEN at high temperature. HPLC-Q/TOF MS and NMR evidence showed that non-reversible hydrolyzate followed decarboxylation was observed in a high-temperature alkali neutralization condition. The results may serve as the scientific basis for the elimination of zearalenone in refined vegetable oils, and provide clues to understanding the oil-safety aspects of elimination of zearalenone.


Assuntos
Óleo de Milho/química , Zea mays/química , Zearalenona/isolamento & purificação , Álcalis
13.
Sci China Life Sci ; 62(11): 1420-1458, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31686320

RESUMO

Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.

14.
Am J Hum Genet ; 105(4): 803-812, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564438

RESUMO

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.


Assuntos
Testes Genéticos/métodos , Perda Auditiva/diagnóstico , Pequim , Teste em Amostras de Sangue Seco , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Masculino
15.
J Cancer ; 10(19): 4707-4718, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528236

RESUMO

Background: Long non-coding RNAs (lncRNAs), which are over 200 nt in length, have a key role in tumorigenesis and disease progression. To explore the role of prognostic lncRNAs in adult acute myeloid leukemia (AML), the expression profiles of lncRNAs and mRNAs in AML were analyzed. Methods: The RNAseq data of 167 adult AML patients and the corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA), which is a publicly available database. The RPKM values of the RNAseq data were subjected to weighted gene co-expression network analysis (WGCNA) in modularization. Results: We identified survival specific lncRNAs and mRNAs, which were divided into modules by coexpression analysis. The lncRNAs were mainly annotated into "Fc gamma R-mediated phagocytosis". The hub lncRNA and co-expressed mRNAs were further selected for analysis of risk stratification. LncRNA-LOC646762 may contribute to AML through the "endocytosis" signaling pathway. Finally, the expression levels of LOC646762 and co-expressed CCND3, CBR1, C10orf54, CD97 and BLOC1S1 in the adult AML patients and healthy volunteers were validated by qRT-PCR, and then their roles in prognosis and risk stratification were identified. Conclusions: Prognostic lncRNA-LOC646762, which may contribute to AML through the "endocytosis" signaling pathway, may act as a biomarker for predicting the survival of adult AML patients, as well as for risk stratification.

16.
J Agric Food Chem ; 67(39): 10904-10912, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31508953

RESUMO

High-order multiple emulsions are of great interest in both fundamental research and industrial applications as vehicles for their encapsulation capability of actives. In this work, we report a hierarchically multicompartmental highly stable triple emulsion by emulsifying and assembling of natural Quillaja saponin. Water-in-oil-in-(oil-in-water) (W2/O2/(O1/W1)) triple emulsion indicates that the compartmented system consisted of surfaced saponin-coated nanodroplets (SNDs) and dispersed oil globules, which in turn contained smaller aqueous droplets. The effects of formulation parameters, including lipophilic emulsifier content, oil fraction, and SND concentration, on the formation of multiple emulsions were systematically investigated. The assembly into fibrillar network of SNDs at the outer oil-water interface effectively protected the triple emulsion droplets against flocculation and coalescence, and strongly prevented the osmotic-driven water diffusion between the internal water droplets and the external water phase, thus contributing to superior stability during 180 days storage. All of these characteristics make the multicompartmentalized emulsions suitable to co-encapsulate a hydrophilic bioactive (gardenia blue) and two hydrophobic bioactives (eapsanthin and curcumin) in a single emulsion droplet hierarchically for the segregation and protection of multiple cargos. This approach offers a promising route toward accessing the next generation of functional deliveries and encapsulation strategies.


Assuntos
Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Extratos Vegetais/química , Quillaja/química , Saponinas/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Emulsificantes/química , Emulsões/química , Glucosídeos/química , Óleos/química , Tamanho da Partícula , Água/química
17.
Food Funct ; 10(8): 4522-4532, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31355399

RESUMO

Delivery systems with multicompartmental structures that allow simultaneous delivery of several cargos are of great interest in both fundamental research and industrial applications. Here, we report a facile and easily scalable approach to fabricate multi-compartmentalized microdroplets for achieving programmed release of hydrophobic cargoes. Well-dispersed nanodroplets stabilized by natural Quillaja saponin served as an effective colloid stabilizer for fabricating microscale emulsion droplets with multicompartment architectures comprising many nanoscale droplets as a shell and single microscale core. Control of the number of nanodroplets allows accurate manipulation of the interface permeability for flexible and controllable release of volatile compounds (e.g., 2,3-butanedione, cis-3-hexen-1-ol, ethyl butyrate, d-limonene). More interestingly, the multicompartment microdroplets exhibited a higher flexibility for programmed release of different volatile compounds, as well as curcumin, during in vitro digestion by introducing cargos into the shell subcompartments or core microcompartment. The promising results highlight the power of this multi-compartmentalized system toward accessing a powerful platform for functional cargo delivery strategies.


Assuntos
Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Extratos Vegetais/química , Quillaja/química , Saponinas/química , Digestão , Sistemas de Liberação de Medicamentos/instrumentação , Emulsões/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula
18.
World Neurosurg ; 131: e247-e254, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31349073

RESUMO

OBJECTIVE: To explore the performance of neurite orientation dispersion and density imaging (NODDI) in grading gliomas and to evaluate the cellular proliferation. METHODS: NODDI and diffusion-weighted imaging were performed on 79 patients with histopathologically proven gliomas. Parameter maps of intracellular volume fraction (ICVF), orientation dispersion index (ODI), and apparent diffusion coefficient (ADC) were calculated. Regions of interest were placed in the most solid part of the tumor. These metrics were normalized to the contralateral normal-appearing white matter and correlated with Ki-67 expression. RESULTS: ICVF and ODI increased as tumor grades increased, whereas ADC decreased with the increase of tumor grades. Significant differences in normalized ICVF and ODI were observed between low-grade gliomas and high-grade gliomas (ICVF: 0.208 ± 0.104 vs. 0.718 ± 0.234; ODI: 0.952 ± 0.428 vs. 1.767 ± 0.636, P < 0.001, respectively) and between grades II and III (ICVF: 0.208 ± 0.104 vs. 0.603 ± 0.253; ODI: 0.952 ± 0.428 vs. 1.762 ± 0.542, P < 0.001, respectively). Normalized ICVF was also significantly different between grades III and IV (0.603 ± 0.253 vs. 0.803 ± 0.182, P = 0.004). Ki-67 labeling index was positively correlated with normalized ICVF and ODI (r = 0.755 and 0.572, P < 0.001, respectively), and negatively correlated with normalized ADC (r = -0.709, P < 0.001). CONCLUSIONS: NODDI is a promising method in grading gliomas and predicting cellular proliferation. These results may be of great significance for the clinical diagnosis and treatment of gliomas.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Neuritos/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Proliferação de Células , Imagem de Difusão por Ressonância Magnética , Glioma/diagnóstico por imagem , Glioma/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Gradação de Tumores
19.
Artif Cells Nanomed Biotechnol ; 47(1): 1833-1838, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31062617

RESUMO

This study aimed to explore the effect of cell division cycle protein 42 (CDC42) on inflammatory response and immune response in mice bearing inflammatory bowel disease (IBD). Trinitrobenzene sulfonic acid was injected into the colon of mice to establish IBD model. The mice were divided into four groups (n = 4): control, model, Ad5, and Ad5-CDC42. After establishing IBD model, mice which were treated with AD5 empty vector and AD5-CDC42 expression vector served as the Ad5 group and Ad5-CDC42 group, respectively. The mRNA and protein levels of interleukin 10 (IL-10), interferon-γ (IFN-γ), IL-4, and tumor necrosis factor-α (TNF-α) in the colon tissues were evaluated by RT-PCR and western blot, respectively. Their levels in the serum and colon tissues were examined by ELISA assay and immunohistochemical analysis, respectively. Their changes in the mRNA and protein levels were consistent and similar changes in the colon tissues and the serum were found among various groups. The levels of IL-10, IFN-γ, IL-4, and TNF-α were lowest in the control group. Their levels in the model group and the Ad5 group were similar (p > .05) and significantly higher than those in the control group (p < .05). In comparison with the model group and the Ad5 group, their levels were significantly reduced in the Ad5-CDC42 group (p < .05). In conclusion, the levels of inflammatory cytokines were elevated in the colon tissues and serum of IBD mice, which could be reduced by the CDC42 treatment. CDC42 regulated the inflammatory response and the innate immune response in IBD mice.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Animais , Colo/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Proc Natl Acad Sci U S A ; 116(24): 11776-11785, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31123148

RESUMO

The cytoplasmic coat protein complex-II (COPII) is evolutionarily conserved machinery that is essential for efficient trafficking of protein and lipid cargos. How the COPII machinery is regulated to meet the metabolic demand in response to alterations of the nutritional state remains largely unexplored, however. Here, we show that dynamic changes of COPII vesicle trafficking parallel the activation of transcription factor X-box binding protein 1 (XBP1s), a critical transcription factor in handling cellular endoplasmic reticulum (ER) stress in both live cells and mouse livers upon physiological fluctuations of nutrient availability. Using live-cell imaging approaches, we demonstrate that XBP1s is sufficient to promote COPII-dependent trafficking, mediating the nutrient stimulatory effects. Chromatin immunoprecipitation (ChIP) coupled with high-throughput DNA sequencing (ChIP-seq) and RNA-sequencing analyses reveal that nutritional signals induce dynamic XBP1s occupancy of promoters of COPII traffic-related genes, thereby driving the COPII-mediated trafficking process. Liver-specific disruption of the inositol-requiring enzyme 1α (IRE1α)-XBP1s signaling branch results in diminished COPII vesicle trafficking. Reactivation of XBP1s in mice lacking hepatic IRE1α restores COPII-mediated lipoprotein secretion and reverses the fatty liver and hypolipidemia phenotypes. Thus, our results demonstrate a previously unappreciated mechanism in the metabolic control of liver protein and lipid trafficking: The IRE1α-XBP1s axis functions as a nutrient-sensing regulatory nexus that integrates nutritional states and the COPII vesicle trafficking.


Assuntos
Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo , Endorribonucleases/metabolismo , Nutrientes/metabolismo , Transporte Proteico/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Movimento Celular/fisiologia , Imunoprecipitação da Cromatina/métodos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Lipídeos/fisiologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/fisiologia
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