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1.
Cell Commun Signal ; 17(1): 100, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429764

RESUMO

BACKGROUND: Androgen receptor (AR) plays important role in the development, progression, and metastasis of prostate cancer (PCa). Caffeic acid phenethyl ester (CAPE) is the main component of honey bee propolis. We determined if CAPE affects the signaling and stability of AR in PCa cells. METHODS: Effects of CAPE on AR transcriptional activity and localization were determined by reporter gene assay and immunofluorescent microscopy. Western blotting, fluorescent polarization, computer simulation, and animal experiment were performed to investigate the molecular mechanism how CAPE reduces the stability of AR. RESULTS: CAPE treatment dose-dependently suppressed the transcriptional activity of AR as well as the protein levels of AR and its target gene PSA. Cyclohexamide treatment revealed that androgen stabilized AR protein, but AR stability was diminished by CAPE. Fluorescence microscopy demonstrated that androgen promoted the nucleus translocation of AR in PCa cells, while treatment with CAPE reduced protein level of AR in both nucleus and cytoplasm. CAPE treatment suppressed the phosphorylation of Ser81 and Ser213 on AR, which regulates the stability of AR. CDK1 and AKT are the kinases phosphorylating Ser81 and Ser213 on AR, respectively. CAPE treatment significantly reduced the protein level and activity of CDK1 and AKT in PCa cells. Overexpression of CDK1 or AKT rescued the AR protein level under CAPE treatment. CONCLUSIONS: Our results suggested that CAPE treatment reduced AR stability and AR transcriptional activity in PCa cells, implying the possibility of using CAPE as a treatment for advanced PCa.

2.
Phytomedicine ; 64: 153068, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31419729

RESUMO

BACKGROUND: Androgen ablation therapy is the primary treatment for metastatic prostate cancer (PCa). However, the majority of PCa patients receiving the androgen deprivation therapy develop recurrent castration-resistant prostate cancer (CRPC) within two years. Chemotherapies show little effect on prolonging survival of CRPC patients and new treatments are needed. Previous studies reported that the extracts from rooibos (Aspalathus linearis) exhibit chemopreventive properties in some cancer models, including skin, liver and oesophagus cancers in animals. We therefore investigate if extracts from rooibos can suppress the proliferation of CRPC cells. PURPOSE: We investigated whether an aspalathin-rich green rooibos extract (GRT™; 12.78 g aspalathin/100 g extract) demonstrates anti-cancer activity against CRPC cells. METHODS: High performance liquid chromatography (HPLC) was used to profile the major flavonoids in GRT. Hoechst-dye proliferation assay, 3,4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) viability assay and flow cytometry assay were used to explore the effects of GRT on the proliferation and cell cycle progression of CRPC cells. Comet assay was used to survey whether GRT induces apoptosis in CRPC cells. LNCaP 104-R1 xenograft nude mice model was used to determine the inhibitory effect of GRT on CRPC tumors in vivo. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism. RESULTS: GRT contained aspalathin as the most abundant flavonoid. GRT suppressed the proliferation and survival of LNCaP 104-R1, LNCaP FGC and PC-3 PCa cells. Flow cytometry analysis showed that GRT decreased the population of PCa cells in S phase but increased the cell population in G2/M phase. Comet assay confirmed that GRT induced apoptosis in LNCaP 104-R1 cells. Gavage of 400 mg/kg GRT suppressed LNCaP 104-R1 xenografts in castrated nude mice. MWA and Western blot analysis indicated that GRT treatment suppressed Akt1, phospho-Akt Ser473, Cdc2, Bcl-2, TRAF4 and Aven, but increased activated Caspase 3, cytochrome c, and p27Kip1. Overexpression of Akt rescued the suppressive effects of GRT on CRPC cells. Co-treatment of GRT with Bcl-2 inhibitor ABT-737, PI3K inhibitor LY294002 and Akt inhibitor GSK 690693 exhibited additive inhibitory effect on proliferation of CRPC cells. CONCLUSIONS: GRT suppresses the proliferation of CRPC cells via inhibition of Akt signaling.

3.
Sci Total Environ ; 684: 78-88, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31150878

RESUMO

Food restriction may cause severe biological effects on wildlife and lead to population decline and extinction. The objective of the current study was to examine the metabolic effects on green sturgeon in response to feed restriction. Green sturgeon fingerlings were fed for two weeks at 12.5, 25, 50 and 100% of the optimum feeding rate (OFR), which corresponded to 0.25, 0.50, 1.00, and 2.00% body weight per day. We characterized the changes in hydrophilic and hydrophobic metabolites from extracts of muscle, liver, and kidney using nuclear magnetic resonance spectroscopy followed by multivariate statistical analysis. The results of principal component analysis (PCA) score plots from the analyses of hydrophilic metabolites showed that they exhibited a greater response to feed restriction than hydrophobic metabolites. In general, the hydrophilic metabolites in tissues from fish fed ≦25% of the OFR were separated from those fed 100% of the OFR in the PCA score plots. Among the three types of tissues examined, the overall metabolite changes showed a greater response to feed restriction in kidney tissue than in liver or muscle tissues. Numerous glucogenic amino acids in muscle and most amino acids in the kidney were decreased under feed restriction conditions. A significant decrease in ketone bodies (3-hydroxyisobutyrate) was observed in the muscle. Most fatty acids except for glycerol, phospholipid and cholesterol in the liver and kidney tissues were decreased under feed restriction conditions. Creatine phosphate, taurine and glycine were also significantly increased in tissues under feed restriction conditions. In conclusion, this study suggests that the manipulation of feed restriction under the current conditions perturbed metabolites related to energy metabolism, osmolality regulation, and antioxidation capacity in the sturgeon.


Assuntos
Ração Animal/análise , Dieta/veterinária , Metabolismo Energético , Peixes/metabolismo , Privação de Alimentos , Adaptação Fisiológica , Animais , Distribuição Aleatória
4.
Molecules ; 24(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027344

RESUMO

The objective of this study was to identify novel acetylation (Ac) modifications of the C1-inhibitor (C1-INH) and explain the association of the levels of autoantibodies against acetylated C1-INH peptides with the risk of developing systemic lupus erythematosus (SLE). Ac modifications of the C1-INH were identified and validated through in-gel digestion, nano-liquid chromatography-tandem mass spectrometry, immunoprecipitation, and Western blotting by using serum protein samples obtained from patients with SLE and age-matched healthy controls (HCs). In addition, the levels of serum C1-INH, Ac-protein adducts, and autoantibodies against unmodified and acetylated C1-INH peptides were measured. C1-INH levels in patients with SLE were significantly lower than those in HCs by 1.53-fold (p = 0.0008); however, Ac-protein adduct concentrations in patients with SLE were significantly higher than those in HCs by 1.35-fold (p = 0.0009). Moreover, immunoglobulin M (IgM) anti-C1-INH367-385 Ac and IgA anti-C1-INH367-385 Ac levels in patients with SLE were significantly lower than those in HCs. The low levels of IgM anti-C1-INH367-385 (odds ratio [OR] = 4.725, p < 0.001), IgM anti-C1-INH367-385 Ac (OR = 4.089, p = 0.001), and IgA anti-C1-INH367-385 Ac (OR = 5.566, p < 0.001) indicated increased risks for the development of SLE compared with HCs.


Assuntos
Proteína Inibidora do Complemento C1/imunologia , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Peptídeos/imunologia , Acetilação , Sequência de Aminoácidos , Autoanticorpos/imunologia , Autoantígenos/imunologia , Proteína Inibidora do Complemento C1/química , Proteína Inibidora do Complemento C1/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Peso Molecular , Peptídeos/química , Ligação Proteica/imunologia , Curva ROC , Taiwan
5.
Cells ; 8(4)2019 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-30935014

RESUMO

Patients receiving docetaxel developed a drug resistance within a few months. We generated docetaxel-resistant PC/DX25 and DU/DX50 CRPC cells from PC-3 and DU-145 PCa cells, respectively. We investigated the mechanism behind why PC/DX25 and DU/DX50 cells exhibited higher migration and invasion ability. Transwell assays were used to measure the migration and invasion of PCa cell. Fluorescence activated cell sorter (FACS) analysis was used to determine the population of cancer stem cell (CSC)-like cell. Micro-Western Array (MWA) was used to study the changes of the protein profile. FACS analysis revealed that PC/DX25 cells and DU/DX50 cells contain higher CD44+ population. MWA and Western blotting assay revealed that protein expression of CD44, YAP, CYR61, CTGF, phospho-ERK1/2 T202/Y204, ERK and vimentin was elevated in PC/DX25 cells. Knockdown of CD44 or YAP suppressed migration and invasion of PC/DX25 and DU/DX50 cells. Knockdown of CD44 decreased expression of YAP, CTGF and CYR61 but increased phosphorylation of S127 on YAP. CD44 knockdown also suppressed protein level of AKT, phospho-AKT T308, phospho-ERK1/2 T202/Y204 and vimentin. CD44 promotes migration and invasion of docetaxel-resistant PCa cells probably via induction of Hippo-Yap signaling pathway and CD44/YAP pathway may be a therapeutic target for docetaxel-resistant PCa.

7.
Cell Microbiol ; : e12981, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30428163

RESUMO

Xenophagy, also known as antibacterial autophagy, plays a role in host defense against invading pathogens such as Group A Streptococcus (GAS) and Salmonella. In xenophagy, autophagy receptors are used in the recognition of invading pathogens and in autophagosome maturation and autolysosome formation. However, the mechanism by which autophagy receptors are regulated during bacterial infection remains poorly elucidated. In this study, we identified LAMTOR2 and LAMTOR1, also named p14 and p18, respectively, as previously unrecognized xenophagy regulators that modulate the autophagy receptor TAX1BP1 in response to GAS and Salmonella invasion. LAMTOR1 was localized to bacterium-containing endosomes, and LAMTOR2 was recruited to bacterium-containing damaged endosomes in a LAMTOR1-dependent manner. LAMTOR2 was dispensable for the formation of autophagosomes targeting damaged membrane debris surrounding cytosolic bacteria, but it was critical for autolysosome formation, and LAMTOR2 interacted with the autophagy receptors NBR1, TAX1BP1, and p62 and was necessary for TAX1BP1 recruitment to pathogen-containing autophagosomes. Notably, knockout of TAX1BP1 caused a reduction in autolysosome formation and subsequent bacterial degradation. Collectively, our findings demonstrated that the LAMTOR1/2 complex is required for recruiting TAX1BP1 to autophagosomes and thereby facilitating autolysosome formation during bacterial infection.

8.
Photoacoustics ; 12: 67-74, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30450281

RESUMO

The gold-standard periodontal probe is an aging tool that can detect periodontitis and monitor gingival health but is highly error-prone, does not fully characterize the periodontal pocket, and causes pain. Photoacoustic imaging is a noninvasive technique that can address these limitations. Here, a range of ultrasound frequencies between 16-40 MHz were used to image the periodontium and a contrast medium based on cuttlefish ink was used to label the pockets. A 40 MHz ultrasound frequency could spatially resolve the periodontal anatomy, including tooth, gum, gingival margin, and gingival thickness of tooth numbers 7-10 and 22-27. The photoacoustic-ultrasound measurements were more precise (0.01 mm) than those taken with physical probes by a dental hygienist. Furthermore, the full geometry of the pockets could be visualized with relative standard deviations of 10% (n = 5). This study shows the potential for non-invasive monitoring of periodontal health with photoacoustic-ultrasound imaging in the dental clinic.

9.
Oncogene ; 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30390070

RESUMO

In the published version of this paper the author Shu-Pin Huang's surname was incorrectly given as Hwang instead of Huang. This has now been corrected in the HTML and PDF versions of the paper.

10.
Zoo Biol ; 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30457161

RESUMO

Integrating multifactor blood analysis is a key step toward a precise diagnosis of the health status of marine mammals. Variations in the circulating lipid profile reflect changes in the metabolism and physiology of an individual. To demonstrate the practicability of lipid profiling for physiological assessment, the phosphorylcholine-containing lipids in the plasma of long-term managed beluga whales (Delphinapterus leucas) were profiled using a lipidomics methodology. Using a multivariate analysis, the mean corpuscular volume, cholesterol, potassium, and γ-glutamyltranspeptidase levels were well modeled with the lipid profile of the female whales. In the models, the correlated lipids provided information about blood parameter-related metabolism and physiological regulation, in particular relating to cholesterol and inflammation. In the males, the levels of cholesterol, triglycerides, blood urea nitrogen, creatinine, plasma iron, and segmented neutrophil were well modeled with the lipid profile. In addition to providing information about the related metabolism and regulation, through a cross-linked analysis of the blood parameters, the correlated lipids indicated a parallel regulation involved in the energy metabolism of the male whales. Lipidomics as a method for revealing the context of physiological change shows practical potential for the health care of managed whales.

11.
PLoS One ; 13(10): e0204829, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30273358

RESUMO

Naphthalene causes mouse airway epithelial injury. However, repeated exposures of naphthalene result in mouse airway tolerance. Previous results showed that toxicity or tolerance was correlated with changes of phosphorylcholine-containing lipids. In this study, a mass spectrometry-based lipidomic approach was applied to examine the effects of naphthalene-induced injury or tolerance in the male ICR mice. The injury model was vehicle x 7 plus 300 mg/kg naphthalene while the tolerant one was 200 mg/kg daily x 7 followed by 300 mg/kg naphthalene on day 8. The lung, liver, kidney, and serum samples were collected for profiles of phosphorylcholine-containing lipids including phosphatidylcholines (PCs) and sphingomyelins (SMs). A partial least-square-discriminate analysis model showed different lung phosphorylcholine-containing lipid profiles from the injured, tolerant, and control groups. Perturbation of diacyl-PCs and plasmenylcholines may be associated with enhanced membrane flexibility and anti-oxidative mechanisms in the lungs of tolerant mice. Additionally, alterations of lyso-PCs and SMs may be responsible for pulmonary dysfunction and inflammation in the lungs of injured mice. Moreover, serum PC(16:0/18:1) has potential to reflect naphthalene-induced airway injuries. Few phosphorylcholine-containing lipid alterations were found in the mouse livers and kidneys across different treatments. This study revealed the changes in lipid profiles associated with the perturbations caused by naphthalene tolerance and toxicity; examination of lipids in serum may assist biomarker development with the potential for application in the human population.

12.
Oncogene ; 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30266990

RESUMO

Recurrent and hormone-refractory prostate cancer (PCA) exhibits aggressive behaviors while current therapeutic approaches show little effect of prolonging the survival of patients with PCA. Thus, a deeper understanding of the patho-molecular mechanisms underlying the disease progression in PCA is crucial to identify novel diagnostic and/or therapeutic targets to improve the outcome of patients. Recent evidence suggests that activation of Wnt signaling in cancer stem cells (CSCs) contributes to cancer progression in malignant tumors. Here, we report that a novel Wnt co-activator ASPM (abnormal spindle-like microcephaly associated) maintains the prostate CSC subpopulation by augmenting the Wnt-ß-catenin signaling in PCA. ASPM expression is incrementally upregulated in primary and metastatic PCA, implicating its potential role in PCA progression. Consistently, downregulation of ASPM expression pronouncedly attenuated the proliferation, colony formation, and the invasive behavior of PCA cells, and dramatically reduced the number of ALDH+ CSCs and inhibited cancer stemness and tumorigenicity. Mechanistically, ASPM interacts with disheveled-3 (Dvl-3), a cardinal upstream regulator of canonical Wnt signaling, and inhibits its proteasome-dependent degradation, thereby increasing its protein stability and enabling the Wnt-induced ß-catenin transcriptional activity in PCA cells. In keeping with the role of ASPM as a CSC-regulator, ASPM co-localizes with ALDH in PCA tissues and its expression exhibits high intra-tumoral heterogeneity. The proportion of high-ASPM-expressing cells in the tumor inversely correlates with the relapse-free survival of PCA patients. Collectively, our data points to ASPM as a novel oncoprotein and an essential regulator of Wnt signaling and cancer stemness in PCA, which has important clinical and therapeutic significance.

13.
Cancer Sci ; 109(11): 3564-3574, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30142696

RESUMO

Androgen receptor (AR), an androgen-activated transcription factor, belongs to the nuclear receptor superfamily. AR plays an important role in the development and progression of prostate cancer (PCa). However, the role of AR in PCa metastasis is not fully understood. To investigate the role of AR in PCa metastasis, we examined AR expression level in primary and metastatic PCa by analyzing gene array data of 378 primary prostate tumors and 120 metastatic prostate tumors from Oncomine, as well as carrying out immunohistochemical (IHC) staining of 56 prostate cancer samples. Expression of mRNA and protein of AR as well as its target gene prostate-specific antigen (PSA) was much higher in metastatic prostate tumors than in primary prostate tumors. Knockdown of AR with siRNA or treating with anti-androgen Casodex reduced migration and invasion ability of C4-2B PCa cells. Knockdown of AR increased protein expression of E-cadherin and AR coregulator KAT5 but reduced expression of epithelial-mesenchymal transition (EMT) marker proteins Slug, Snail, MMP-2, vimentin, and ß-catenin. Knockdown of KAT5 increased migration of C4-2B cells, whereas overexpression of KAT5 suppressed cell migration. KAT5 knockdown rescues the suppressive effect of AR knockdown on migration of C4-2B cells. Gene expression level of AR and KAT5 showed a negative correlation. PCa patients with higher AR expression or lower KAT5 expression correlated with shorter recurrence-free survival. Our study suggested that elevation of AR expression and AR signaling in prostate tumors promotes PCa metastasis by induction of EMT and reduction of KAT5.


Assuntos
Lisina Acetiltransferase 5/genética , Neoplasias da Próstata/genética , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Regulação para Cima , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Lisina Acetiltransferase 5/metabolismo , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/metabolismo , Análise de Sobrevida
14.
Eur J Clin Invest ; 48(6): e12937, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29675916

RESUMO

BACKGROUND: Among multiple causes, diabetic nephropathy (DN) is the major underlying renal disease that leads to end-stage renal disease (ESRD), and early diagnosis can effectively prevent or delay the progression to ESRD. Therefore, the current study aimed to develop noninvasive, accurate detection markers. MATERIALS & METHODS: For this study, 62 diabetes mellitus (DM) patients, 59 DN patients and 21 healthy controls (HCs) were recruited. All participants' serum samples were subjected to concavanalin (Con) A affinity chromatography, which utilizes glycoproteins to discover potential markers. RESULTS: From nano LC-MS and Western blot analysis, apolipoprotein A-IV (ApoA4) was selected which featured a gradual, almost twofold increase in the order of HC, DM and DN. In the Con A-based ELISA, the DM group was 1.91-fold higher than the HC group, while the DN group was 2.56-fold higher than the HCs and 1.33-fold higher than the DM group. In addition, significant positive correlations were observed between ApoA4 and blood urea nitrogen levels and between ApoA4 and creatine levels, while significant negative correlations were seen between serum protein levels and between serum albumin levels in comparisons of DM and DN samples. CONCLUSIONS: Serum Con A-bound ApoA4 levels were higher in the DM group than in HCs, and further increased in the DN group. Levels of ApoA4 were positively correlated with blood urea nitrogen and creatine, but negatively correlated with serum protein and albumin. This evidence supports serum Con A-bound ApoA4 as a circulating marker for predicting the progression of renal impairment in DM patients.


Assuntos
Apolipoproteínas A/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Idoso , Proteínas Sanguíneas/metabolismo , Nitrogênio da Ureia Sanguínea , Western Blotting , Estudos de Casos e Controles , Cromatografia Líquida , Concanavalina A/metabolismo , Creatinina/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Prognóstico , Albumina Sérica/metabolismo
15.
Nanotoxicology ; 12(5): 439-452, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29635945

RESUMO

Zinc oxide (ZnO) nano- and fine-sized particles are associated with respiratory toxicity in humans, but the underlying molecular mechanisms remain unclear. Our previous nuclear magnetic resonance-based metabolomic study demonstrated that changes in phosphorylcholine-containing lipids (PC-CLs) in the respiratory system were associated with ZnO particle-induced respiratory toxicity. However, the details of the lipid species associated with adverse effects and possible biomarker signatures have not been identified. Thus, a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics platform was applied to examine the alterations of PC-CL species in the lungs of rats treated with a series of concentrations of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles via inhalation. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and the Mann-Whitney U (MWU) test with false discovery rate (FDR) control were conducted to explore the perturbed lipid species and to discriminate a potential pulmonary biomarker signature after ZnO particle exposure. The PCA and PLS-DA models revealed that the fine-sized ZnO particle-treated groups and the high-concentration nano-sized group were separated from the control groups as well as from the low and moderate nano-sized groups. The results from the MWU test further suggested that after FDR adjustment, numerous PC-CL species were altered in the high-concentration and moderate-concentration fine-sized groups. Furthermore, our results suggested that lipids involved in anti-oxidation, membrane conformation, and cellular signal transduction were altered in response to ZnO-induced oxidative stress and inflammation. One lipid, PC(18:0/18:1), exhibited good performance (AUC > 0.8) of discriminative ability in distinguishing ZnO particle exposure from the control. These findings not only provide a foundation for the exploration of possible ZnO particle-mediated mechanisms but also suggest a lipid biomarker for ZnO particle exposure.

16.
Mol Oncol ; 12(5): 756-771, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29603594

RESUMO

Glioblastoma multiforme (GBM) is a highly malignant type of brain tumor found in humans. GBM cells reproduce quickly, and the median survival time for patients after therapy is approximately 1 year with a high relapse rate. Current therapies and diagnostic tools for GBM are limited; therefore, we searched for a more favorable therapeutic target or marker protein for both therapy and diagnosis. We used mass spectrometry (MS) analysis to identify GBM-associated marker proteins from human plasma and GBM cell cultures. Additional plasma and 52 brain tissues obtained from patients with gliomas were used to validate the association rate of serum amyloid A1 (SAA1) in different grades of gliomas and its distribution in tumors. Microarray database analysis further validated the coefficient of SAA1 levels in gliomas. The cellular mechanisms of SAA1 in GBM proliferation and infiltration were investigated in vitro. We analyzed the correlation between SAA1 and patients' medication requirement to demonstrate the clinical effects of SAA1 in GBM. SAA1 was identified from MS analysis, and its level was revealed to be correlated with the disease grade, clinical severity, and survival rate of patients with gliomas. In vitro cultures, including GBM cells and normal astrocytes, revealed that SAA1 promotes cell migration and invasion through integrin αVß3 to activate the Erk signaling pathway. Magnetic resonance imaging and tumor region-specific microarray analysis identified a correlation between SAA1 and GBM cell infiltration in patients. In summary, our results demonstrate that SAA1 in combination with integrin αV and ß3 can serve as an indicator of high glioblastoma risk. We also identified the cellular mechanisms of SAA1 contributing to GBM progression, which can serve as the basis for future GBM therapy.

17.
Clin Biochem ; 56: 75-82, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29680706

RESUMO

OBJECTIVE: Advanced glycation end products (AGEs) are involved in the pathogenesis of Alzheimer's disease (AD). Specific AGEs and related autoantibodies may be early AD markers. Apolipoprotein A1 (ApoA1) and its post-translational modifications (PTMs) are associated with neurodegeneration and thus selected to test the hypothesis. METHODS: Serum samples from totally 64 AD or health control (HC) Taiwanese were analyzed. ApoA1 was isolated from the serum and examined through LC-MS/MS and PTM analyses. A specific AGE and its autoantibodies were determined using Western blotting or ELISA. RESULTS: Nε-(Carboxyethyl)lysine (CEL) modification, a kind of AGEs, was identified on ApoA1 peptide 141-QKVEPLR-147 (ApoA1141-147) from AD serum. Total CEL adducts and autoantibodies against CEL on ApoA1141-147 were significantly increased in AD samples. The area under the receiver operating characteristic curve was 0.965 for anti-CEL-ApoA1141-147 IgM. Mini Mental State Examination scores of the AD patients were positively correlated with anti-CEL-ApoA1141-147 IgM, suggesting that the IgM level is high in early AD pathology and decreased with disease progression. CONCLUSION: CEL modification was increased on AD serum proteins including ApoA1, leading to an elevated anti-CEL IgM in early disease state. Both CEL and anti-CEL IgM may serve as AD biomarkers.


Assuntos
Doença de Alzheimer/sangue , Apolipoproteína A-I/antagonistas & inibidores , Autoanticorpos/sangue , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Imunoglobulina M/análise , Processamento de Proteína Pós-Traducional , Regulação para Cima , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/imunologia , Doença de Alzheimer/metabolismo , Especificidade de Anticorpos , Apolipoproteína A-I/sangue , Apolipoproteína A-I/química , Autoimunidade , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/química , Humanos , Lisina/análogos & derivados , Lisina/sangue , Lisina/química , Masculino , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/química , Escalas de Graduação Psiquiátrica , Curva ROC , Taiwan
19.
Colloids Surf B Biointerfaces ; 165: 172-181, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29482128

RESUMO

The development of stimuli-responsive drug carrier systems enabling to deliver high doses of anti-cancer drugs to tumor tissues is still urgently needed. In this study, we report the preparation of reduction-responsive methoxypolyethylene glycol-block-(poly(l-lysine)-co-poly(l-tyrosine)) (mPEG-b-(PLL-co-PLY)) nanoparticles (NPs) exhibiting sizes smaller than 100 nm and high drug loading content (DLC) of doxorubicin (DOX) by selecting the Lys and Tyr residues as the polypeptide building blocks. The disulfide-cross-linked mPEG-b-(PLL-co-PLY) assemblies with sizes can be tuned by varying the polypeptide composition followed by subsequent disulfide-cross-linking. Cytotoxicity assays showed that the Dox-loaded NPs exhibited efficient cell internalization and proliferation inhibition toward cancer cells, whereas the copolymers exhibited low hemolysis to human red blood cells and excellent biocompatibility to both normal and cancer cells. The enhanced internalization and cytotoxicity of DOX-NPs can be possible due to their small size and their reduction-responsive property. Anticancer studies using C57BL/6 mice bearing LLC tumor model showed that the DOX-loaded NPs significantly suppressed tumor growth and prolonged the survival of tumor-bearing mice without obvious body weight loss and damage to major organs. This approach provides a platform for developing stimuli-responsive, polypeptide-based drug delivery systems with high DLC for cancer treatment.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Doxorrubicina/farmacologia , Portadores de Fármacos , Glutationa/metabolismo , Nanopartículas/química , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Lewis/mortalidade , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dissulfetos/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Composição de Medicamentos/métodos , Endocitose , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Oxirredução , Peptídeos/química , Polietilenoglicóis/química , Polilisina/química , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos
20.
Sci Total Environ ; 627: 571-578, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29426181

RESUMO

Coral is commonly selected as a bioindicator of detecting a variety of adverse factors such as photosystem II herbicide Irgarol 1051, through measuring pan-type biomarkers. To improve the effectiveness of biomonitoring, omic technologies have recently been applied to model the systemic changes in an organism. Membrane lipids create a dynamic cell structure based on the physiological state, which offers a distinct lipid profile to specifically detect environmental threats and assess the associated health risk. To demonstrate the potential of a lipidomic methodology for biomonitoring, the glycerophosphocholine (GPC) profiles of the coral Seriatopora caliendrum were observed during 3 days of Irgarol (0.1-2.0 µg/L) exposure. The lipid profile variations were modeled based on the Irgarol dose and the coral photoinhibition levels to develop an excellent quantitative model. The predominant changes correlated with the photoinhibition, decreasing the lyso-GPCs and GPCs with lower unsaturated chains and increasing GPCs with highly polyunsaturated chains, can be related to the consequence of blocking the photosynthetic electron flow based on the associated physiological roles. Other dose-specific lipid changes led to the partial exchange of PC(O-16:0/20:5) for PC(16,0/20:5) as a first-line response to counteract the membrane opening caused by Irgarol. Increased levels of the GPCs with 20:4 or 22:6 chains, which can promote mitochondrial functionality, confirmed an elevated respiration level in the coral exposed to Irgarol levels of >0.5 µg/L. Notably, plasmanylcholines with 20:4 or 22:6 chains and phosphatidylcholines with 22:6 or 22:5 chains, which can alter their membrane material properties to mitigate organelle pre-swelling and swelling in different ways, formed in the coral exposed to the 0.5 and 2.0 µg/L Irgarol levels. Such coral adaptations further predict the health risks associated with altered physiological conditions. In this study, the lipidomic methodology is demonstrated as a potential tool for environmental monitoring and assessment.


Assuntos
Antozoários/efeitos dos fármacos , Monitoramento Ambiental , Triazinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antozoários/fisiologia , Herbicidas/toxicidade , Medição de Risco
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