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1.
Asian J Psychiatr ; 93: 103939, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38350178

ABSTRACT

This study explored the complex triangular relationships between parenting styles, personality traits, and depressive trait in Chinese Han adults (N = 490; Mean age=24.25; 51.0% women), and examined the relationship between parenting styles and brain structure. The data indicated that depressive trait in adulthood were negatively correlated with a favorable parenting style (emotional warmth) and positively correlated with undesirable parenting styles (punishment, rejection, and overprotection/over-intervention). Additionally, depressive trait in adulthood were positively related to neuroticism and psychoticism, and negatively related to extraversion. Using a multiple parallel mediation analysis, we found that neuroticism could be worsened by undesirable parenting styles and ameliorated by favorable parenting styles, and it further mediated the relationship between parenting styles and depressive trait across all models. Psychoticism played a similar role in two models: 1) parental punishment and depressive trait and 2) parental rejection and depressive trait. Extraversion played a mediating role between the father's overprotection and depressive trait. Subgroup analysis showed that different mediating pathways existed between different sexes. In terms of brain structure, we found that gray matter volume of the right inferior frontal gyrus was negatively related to overprotection by the father and positively related to psychoticism. Our findings highlight the importance of parenting style on personality traits, depressive trait, and brain structure over the long term.


Subject(s)
Brain , Parenting , Adult , Humans , Female , Young Adult , Male , Parenting/psychology , Parents , Gray Matter , Personality
2.
Food Sci Biotechnol ; 32(4): 517-529, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36911335

ABSTRACT

Exopolysaccharide (EPS)-producing Bifidobacterium bifidum EPS DA-LAIM was isolated from healthy human feces, the structure of purified EPS from the strain was analyzed, and its prebiotic activity was evaluated. The EPS from B. bifidum EPS DA-LAIM is a glucomannan-type heteropolysaccharide with a molecular weight of 407-1007 kDa, and its structure comprises 2-mannosyl, 6-mannosyl, and 2,6-mannosyl residues. The purified EPS promoted the growth of representative lactic acid bacteria and bifidobacterial strains. Bifidobacterium bifidum EPS DA-LAIM increased nitric oxide production in RAW 264.7 macrophage cells, indicating its immunostimulatory activity. Bifidobacterium bifidum EPS DA-LAIM also exhibited high gastrointestinal tract tolerance, gut adhesion ability, and antioxidant activity. These results suggest that EPS from B. bifidum EPS DA-LAIM is a potentially useful prebiotic material, and B. bifidum EPS DA-LAIM could be applied as a probiotic candidate. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01213-w.

4.
Microorganisms ; 10(12)2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36557684

ABSTRACT

Exopolysaccharide (EPS)-producing Lacticaseibacillus paracasei EPS DA-BACS was isolated from healthy human feces and its probiotic properties, as well as the structure and prebiotic activity of the EPS from this strain were examined. EPS from L. paracasei EPS DA-BACS had a ropy phenotype, which is known to have potential health benefits and is identified as loosely cell-bounded glucomannan-type EPS with a molecular size of 3.7 × 106 Da. EPS promoted the acid tolerance of L. paracasei EPS DA-BACS and provided cells with tolerance to gastrointestinal stress. The purified EPS showed growth inhibitory activity against Clostridium difficile. L. paracasei EPS DA-BACS cells completely inhibited the growth of Bacillus subtilis, Pseudomonas aeruginosa, and Aspergillus brasiliensis, as well as showed high growth inhibitory activity against Staphylococcus aureus and Escherichia coli. Treatment of lipopolysaccharide-stimulated RAW 264.7 cells with heat-killed L. paracasei EPS DA-BACS cells led to a decrease in the production of nitric oxide, indicating the anti-inflammatory activity of L. paracasei EPS DA-BACS. Purified EPS promoted the growth of Lactobacillus gasseri, Bifidobacterium bifidum, B. animalis, and B. faecale which showed high prebiotic activity. L. paracasei EPS DA-BACS harbors no antibiotic resistance genes or virulence factors. Therefore, L. paracasei EPS DA-BACS exhibits anti-inflammatory and antimicrobial activities with high gut adhesion ability and gastrointestinal tolerance and can be used as a potential probiotic.

6.
Food Chem ; 393: 133358, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-35661594

ABSTRACT

Glutenin has limited applicability in food industry due to poor water solubility and emulsifying properties. In this study, the physicochemical properties of glutenin were improved by combined treatments of alkaline pH-shifting or acidic pH with heating. The surface morphology, structure and physicochemical properties were measured during the modification process of glutenin. Results showed that the smaller square clusters and regular tubular fibrils were observed in modified glutenin and the α-helix proportion of the treated glutenin was finally increased to 59.90 ± 0.01%. Compared with untreated glutenin, the combined treatments of pH-shifting with heating as well as fibrillation process increased the solubility of glutenin by 21.3 and 3.5 times, respectively. Moreover, the treated glutenin showed excellent emulsifying stability (EAI: 50.84 ± 0.51 m2g-1) and thermal stability (peak temperature increased from 109.58 to 149.05 °C). This study provides an informative basis for improving the physicochemical and functional properties of glutenin.


Subject(s)
Glutens , Triticum , Acids , Glutens/chemistry , Hydrogen-Ion Concentration , Solubility , Triticum/chemistry
7.
Psychooncology ; 31(1): 70-77, 2022 01.
Article in English | MEDLINE | ID: mdl-34322963

ABSTRACT

OBJECTIVES: To explore the relationship between patient's health literacy and perceived shared decision-making (SDM) among Chinese cancer patients. METHODS: A cross-sectional study was conducted involving a convenience sample of 458 cancer patients from four public hospitals in Guangzhou, China. Patients' self-reported data were collected using the Health Literacy Management Scale (HeLMS) and the nine-item Shared Decision-Making Questionnaire (SDM-Q-9). Hierarchical multiple regressions, controlling for patient-doctor relationship, social support, sociodemographic and clinical variables were conducted to explore the effect of health literacy on perceived SDM. RESULTS: Health literacy itself accounted for 68.0% of the variance in perceived SDM. Higher scores in domains "information acquisition ability," and "communication interaction ability" of HeLMS were significantly associated with a higher level of perceived SDM after controlling the covariates (R2  = 75.7%). CONCLUSIONS: Health literacy, especially the information acquisition ability and communication interaction ability, played a prominent role for Chinese cancer patients to be involved in treatment decision making.


Subject(s)
Health Literacy , Neoplasms , Cross-Sectional Studies , Decision Making , Decision Making, Shared , Humans , Neoplasms/therapy , Patient Participation , Physician-Patient Relations
8.
Cancer Manag Res ; 13: 9049-9062, 2021.
Article in English | MEDLINE | ID: mdl-34938119

ABSTRACT

BACKGROUND: Upregulation of lncRNA BBOX1 antisense RNA 1 (BBOX1-AS1) has been examined in various tumors. However, its role in nasopharyngeal carcinoma (NPC) remains poorly understood. METHODS: RT-qPCR was performed to measure the expression of BBOX1-AS1, KPNA2, and miR-3940-3p. In vitro assays were performed to determine the alteration of cell phenotypes in NPC cells upon transfection or co-transfection with sh-BBOX1-AS1, sh-KPNA2, or miR-3940-3p inhibitor. The BBOX1-AS1-miR-3940-3p and miR-3940-3p-KPNA2 interplay was verified via luciferase reporter and RNA pull-down assays. RESULTS: High BBOX1-AS1 levels were detected in the nasopharyngeal carcinoma tissues. BBOX1-AS1 silencing considerably suppressed the proliferative, migratory, and invasive abilities of NPC cells in vitro. Interestingly, BBOX1-AS1 could specifically bind to miR-3940-3 and abrogate the inhibition of KPNA2 induced by miR-3940-3. Additionally, analysis of tissue samples showed that miR-3940-3 was inversely correlated with BBOX1-AS1 and KPNA2. CONCLUSION: Our findings revealed that the BBOX1-AS1/miR-3940-3/KPNA2 axis is pro-oncogenic in NPC progression, uncovering novel insights into targeted therapy for this disorder.

9.
Am J Transl Res ; 13(8): 9248-9259, 2021.
Article in English | MEDLINE | ID: mdl-34540041

ABSTRACT

Lung cancer is the leading cause of cancer-related death worldwide. In this study, we attempted to identify the common pathogenesis of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) based on a modular and comprehensive analysis method. Data were downloaded and the differences analyzed in LUAD samples, LUSC samples, and normal samples, respectively. Co-expression analysis, enrichment analysis, and hypergeometric testing were used to predict transcription factors (TFs) and ncRNAs, as well as target genes. We obtained 4,596 differentially expressed genes which were clustered into 14 modules dysfunction. The 14 clustered genes (including DOK2, COL5A1, and TSPAN8) were identified as the core genes of the module. Module genes are substantially involved in biological processes, such as extracellular matrix, carbohydrate binding and renal system development, and signal transduction as well, including PPAR signal transduction, cGMP-PKG signal transduction, PI3K-Akt signal transduction, and Apelin signal transduction. We identified ncRNA (miR-335-5p, ANCR, TUG1) and transcription factors (RELA, SP1) to regulate dysfunction module genes essentially. The analysis showed that comprehensive co-expression analysis contributes to understanding the TF ncRNA. Moreover, it assisted in further understanding of the molecular pathogenesis of co-expression of modular genes that regulate LUAD and LUSC. It provided a precious resource and theoretical basis for further experiments.

10.
Support Care Cancer ; 27(2): 583-589, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30022347

ABSTRACT

OBJECTIVES: To study the preferences of cancer patients and their families in way of being informed of their condition and, by comparing their preferences with the medical staff's clinical practices, explore the factors underlying the latter's preferences. METHODS: A survey was conducted with 216 cancer patients, 242 families, and 176 clinical staff members with the Medical Status Communication questionnaire (Simplified Chinese edition). RESULTS: The clinical staff scored lower than the cancer patients and their families in terms of the total score, way of communication, emotional support, and additional information (F = 16.134, p < .001; F = 28.604, p < .001; F = 13.839, p < .001; F = 16.745, p < .001). Factors underlying the medical staff's clinical practices included, as revealed by the multiple linear regression analysis, gender (p = .03), and willingness to improve the way of communication about cancer (p = .006). CONCLUSIONS: A gap existed between the medical staff's clinical practice and the preferences of the cancer patients and their families. The medical staff should receive adequate training in cancer communication skills and techniques for improvement in this respect. When designing training for skills in delivering bad news to cancer patients, the well-being of cancer patients and their families must be thoroughly considered, and patient demands for information should be satisfied in the context of the information explosion of the current age.


Subject(s)
Family/psychology , Medical Staff/ethics , Neoplasms/psychology , Physician-Patient Relations/ethics , Communication , Female , Humans , Male , Surveys and Questionnaires , Truth Disclosure
11.
Comput Math Methods Med ; 2018: 6508319, 2018.
Article in English | MEDLINE | ID: mdl-30344616

ABSTRACT

Early intervention for depression is very important to ease the disease burden, but current diagnostic methods are still limited. This study investigated automatic depressed speech classification in a sample of 170 native Chinese subjects (85 healthy controls and 85 depressed patients). The classification performances of prosodic, spectral, and glottal speech features were analyzed in recognition of depression. We proposed an ensemble logistic regression model for detecting depression (ELRDD) in speech. The logistic regression, which was superior in recognition of depression, was selected as the base classifier. This ensemble model extracted many speech features from different aspects and ensured diversity of the base classifier. ELRDD provided better classification results than the other compared classifiers. A technique for identifying depression based on ELRDD, ELRDD-E, was here suggested and tested. It offered encouraging outcomes, revealing a high accuracy level of 75.00% for females and 81.82% for males, as well as an advantageous sensitivity/specificity ratio of 79.25%/70.59% for females and 78.13%/85.29% for males.


Subject(s)
Depression/diagnosis , Depression/physiopathology , Diagnosis, Computer-Assisted/methods , Logistic Models , Pattern Recognition, Automated , Speech/physiology , Acoustics , Adolescent , Adult , Algorithms , Case-Control Studies , China , Female , Humans , Language , Male , Middle Aged , Models, Statistical , Reproducibility of Results , Sensitivity and Specificity , Sex Factors , Support Vector Machine , Young Adult
12.
Sci Rep ; 8(1): 15953, 2018 10 29.
Article in English | MEDLINE | ID: mdl-30374025

ABSTRACT

Moutan cortex, Angelica Dahurica root, and Bupleurum root are traditional herbal medicines used in Asian countries to treat various diseases caused by oxidative stress or inflammation. Parkinson's disease (PD) has been associated with mitochondrial dysfunction, but no effective treatment for mitochondrial dysfunction has yet been identified. In this study we investigated the neuroprotective effects of the triple herbal extract DA-9805 in experimental models of PD. DA-9805 was prepared by extracting three dried plant materials (Moutan cortex, Angelica Dahurica root, and Bupleurum root in a 1:1:1 mixture) with 90% ethanol on a stirring plate for 24 h at room temperature and fingerprinted using high-performance liquid chromatography. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), which both exert neurotoxic effects on dopaminergic neurons by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) complex I, were used to make experimental models of PD. In MPP+-treated SH-SY5Y cells, DA-9805 ameliorated the suppression of tyrosine hydroxylase expression and mitochondrial damage on OXPHOS complex 1 activity, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and oxygen consumption rate. In the MPTP-induced subacute PD model mice, oral administration of DA-9805 recovered dopamine content as well as bradykinesia, as determined by the rotarod test. DA-9805 protected against neuronal damage in the substantia nigra pars compacta (SNpc) and striatum. In both in vitro and in vivo models of PD, DA-9805 normalized the phosphorylation of AKT at S473 and T308 on the insulin signaling pathway and the expression of mitochondria-related genes. These results demonstrate that the triple herbal extract DA-9805 showed neuroprotective effects via alleviating mitochondria damage in experimental models of PD. We propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics for PD.


Subject(s)
Mitochondria/drug effects , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Angelica/chemistry , Angelica/metabolism , Animals , Bupleurum/chemistry , Bupleurum/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Disease Models, Animal , Dopamine/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Humans , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Neuroprotective Agents/therapeutic use , Paeonia/chemistry , Paeonia/metabolism , Parkinson Disease/drug therapy , Parkinson Disease/pathology , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism
13.
Arch Oral Biol ; 73: 105-112, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27744260

ABSTRACT

OBJECTIVE: To investigate the functional mechanism of microRNA-182 (miR-182) in head and neck squamous cell carcinoma (HNSCC). DESIGN: HNSCC and normal samples were used to check both p53 and miR-182 expression. Two cancer cell lines with overexpression of miR-182 were used to check cell proliferation and migration. In vivo role of miR-182 was assessed using mouse xenograft tumor model. ß-TrCP2 was found to be direct target of miR-182 by luciferase reporter assay. RESULTS: Overexpression of miR-182 was closely related with overproduction of p53 in HNSCC. Overexpression of miR-182 promoted cell proliferation and migration and its oncogenic effect was also confirmed in vivo. ß-TrCP2 acted as direct target of miR-182 and its overexpression can reverse the miR-182 induced cell proliferation and migration. CONCLUSION: Overexpression of TP53 mutation-associated miR-182 may promote tumor cell proliferation and migration in HNSCC and suggest possible biomarker for the prediction of tumor recurrence.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , MicroRNAs/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Humans , Mice , Squamous Cell Carcinoma of Head and Neck , beta-Transducin Repeat-Containing Proteins/metabolism
14.
Zhonghua Zhong Liu Za Zhi ; 36(5): 335-40, 2014 May.
Article in Chinese | MEDLINE | ID: mdl-25030587

ABSTRACT

OBJECTIVE: The aim of this study was to explore the effect of SPARC on the anti-cancer effect of gemcitabine and underlying mechanism in pancreatic cancer. METHODS: After treating with gemcitabine, the proliferation rate of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells was detected by MTT assay. The cell cycle distribution and cell apoptosis in each group were examined by flow cytometry, and the capability of clone formation was tested by adhesion-dependent clone formation assay. The apoptosis-related proteins were analyzed by Western blot. RESULTS: The growth of pancreatic cancer cells was inhibited by gemcitabine in a time-dependent and dose-dependent manner. Its IC50 at 24, 48, and 72-h was (40.1 ± 2.5) µmol/L, (15.0 ± 0.5) µmol/L and (6.6 ± 0.1) µmol/L, respectively. The overexpression of SPARC increased the inhibitory effect of gemcitabine on growth of pancreatic cancer MIA PaCa2/SPARC69 cells, presenting a dose- and time- dependent manner. Its IC50 at 24, 48, 72 h was (24.3 ± 1.5) µmol/L, (7.7 ± 0.3) µmol/L and (4.8 ± 0.2) µmol/L, respectively. The clone formation assay showed that before gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (2350 ± 125), (2130 ± 120) and (1567 ± 11), respectively. After gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 1674 ± 79) , (1587 ± 94) and (557 ± 61), respectively. The overexpression of SPARC enhanced the chemosensitivity of MIA PaCa2 cells to gemcitabine chemotherapy. After treating with 10 µmol/L gemcitabine for 48 h, the ratio of G0/G1 cells in MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (56.0 ± 5.5)%, (55.0 ± 4.5)% and (68.0 ± 7.0)%, respectively. The cells arrested at G0/G1 phase were significantly increased in the MIA PaCa2/SPARC69 cells. The apoptosis rates of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (22.4 ± 2.5)%, (19.9 ± 2.0)% and (37.7 ± 3.9)%, respectively, indicating that overexpression of SPARC enhanced the gemcitabine-induced apoptosis in MIA PaCa2 cells. The Western blot analysis showed that, compared with MIA PaCa2 and MIA PaCa2/V cells, the expression of caspase-2, -8, -9 and cleaved PARP protein was significantly increased, while the expression of Bcl-2 was not changed significantly in the MIA PaCa2/SPARC69 cells. CONCLUSION: SPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Deoxycytidine/analogs & derivatives , Osteonectin/metabolism , Pancreatic Neoplasms , Antimetabolites, Antineoplastic/administration & dosage , Caspase 2/metabolism , Caspase 8/metabolism , Caspase 9/metabolism , Cell Cycle/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cysteine Endopeptidases/metabolism , Deoxycytidine/administration & dosage , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Humans , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Poly(ADP-ribose) Polymerases/metabolism , Time Factors , Gemcitabine
15.
Mol Biotechnol ; 53(2): 198-206, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22351429

ABSTRACT

One of the most rapid and effective defensive mechanisms plants have for protecting themselves, from a variety of biotic and abiotic stresses, is the regulation of plant signal transcription factors. AP2/ERF factors play an important role in plant development as well as in hormonal regulation and cold response. Directed evolution is a powerful tool to modify proteins, improving their properties, and for studying their structure-function relations. Here, the transgenic Arabidopsis plants over-expressed a mutant gene, BnaERF-B3-hy15-mu3, which encoded for a factor that exhibited more binding activity with the GCC box element than the wild-type gene BnaERF-B3-hy15 encode factor, and exhibited more freezing tolerance than transgenic plants containing the original BnaERF-B3-hy15 gene. Real-time PCR analyses also revealed that the expression levels of several stress-regulated genes were altered in the over-expressed BnaERF-B3-hy15-mu3 transgenic lines. The BnaERF-B3-hy15 responded to exogenous ABA. Using RT-PCR analysis, the expression of BnaERF-B3-hy15 at different stages and stress treatments were also analyzed.


Subject(s)
Arabidopsis/genetics , Brassica napus/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Transcription Factor AP-2/metabolism , Adaptation, Physiological , Arabidopsis/metabolism , Carbohydrates , Cold Temperature , Cold-Shock Response , Directed Molecular Evolution , Electrolytes , Gene Expression Regulation, Plant , Plant Proteins/biosynthesis , Plant Proteins/genetics , Plants, Genetically Modified/physiology , Transcription Factor AP-2/biosynthesis , Transcription Factor AP-2/genetics
16.
Article in Chinese | MEDLINE | ID: mdl-24406180

ABSTRACT

OBJECTIVE: To investigate the treatment efficacy of tympanostomy microtube placement surgery for middle ear atelectasis. METHODS: A retrospective analysis was conducted on 26 patients (28 ears) with middle ear atelectasis, who complained fullness or pressure in the ears.Otoscope showed tympanic membrane invagination, scattered or disappeared cone of light, tympanic membrane was pale and dull. The pure tone audiometry air-bone gap >10 dB. Acoustic immittance showed tympanic negative pressure. All the ears had atelectasis of I-III grade. Patients were performed tympanic membrane microtube placement under local anesthesia, and were followed up for 6-12 months. RESULTS: Twenty-five ears recovered from the fullness after operation, in which, 23 ears reverted from type "C" to type "A" in acoustic immittance tests and the pure-tone average (PTA) of hearing thresholds were decreasing from 5 to 20 dB, while 2 ears relapse after removal of the microtube. Three ears with middle ear atelectasis of III grade were ineffectiveness. All the 26 cases had no complications including middle ear infection, tympanosclerosis, and permanent perforation after removal of the microtubes. CONCLUSIONS: The placement of tympanostomy microtube can be used to treat middle ear atelectasis, especially to the patients with middle ear atelectasis of I-II grade as it is effective on elimination of middle ear negative pressure and remission of fullness.


Subject(s)
Ear Diseases/surgery , Ear, Middle , Middle Ear Ventilation/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Tympanic Membrane/surgery
17.
J Pharm Sci ; 100(2): 482-91, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20669330

ABSTRACT

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limitations, which include a weak pharmacokinetic profile, namely, a short biological half-life and rapid renal clearance, and an inability to form a homotrimeric structure. In this research, we attempted to develop a sustained release nanoparticle (NP) formulation that stabilizes Apo2L/TRAIL and preserves its antitumor activity. Apo2L/TRAIL-loaded human serum albumin (HSA) NPs were prepared using a desolvation technique optimized by particle size, zeta-potential, and entrapment efficiency. Apo2L/TRAIL in HSA-NPs continuously released over 24 h at 37°C in phosphate buffered saline and rat plasma condition, and the biological activity of Apo2L/TRAIL-HSA-NPs was preserved (IC(50) = 67.2 ng/mL versus Apo2L/TRAIL IC(50) = 55.4 ng/mL) with negligible activity loss. Furthermore, in vivo pharmacokinetic profiles and tumor distribution demonstrated the superiority of Apo2L/TRAIL-HSA-NPs over Apo2L/TRAIL. The circulating half-life period was significantly prolonged from 9.8 to 90.7 min (9.2-fold enhancement), and drug bioavailability was clearly enhanced on the basis of area under the curve analysis (2.7-fold). And tumor distribution of Apo2L/TRAIL-HSA-NPs was also increased at 1 h after injection, which was about 14-fold (1-h point) over that of Apo2L/TRAIL. These results show that Apo2L/TRAIL-loaded HSA-NPs should be considered as potential long-acting cancer agents.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Delayed-Action Preparations/chemistry , Nanoparticles/chemistry , TNF-Related Apoptosis-Inducing Ligand/administration & dosage , TNF-Related Apoptosis-Inducing Ligand/pharmacokinetics , Animals , Cell Line, Tumor , Humans , Male , Mice , Mice, Inbred C57BL , Nanoparticles/ultrastructure , Neoplasms/drug therapy , Rats , Rats, Sprague-Dawley , Serum Albumin/chemistry
18.
BMB Rep ; 43(8): 567-72, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20797320

ABSTRACT

In this study, we cloned the ERF-B3 subfamily transcription factor gene BnaERF-B3-hy15 from Brassica napus L. Huyou15. This 600 bp gene encodes a 199 amino acid classic ethylene responsive factor (ERF), which shown no binding or very weak binding GCC box-binding activity by the yeast one-hybrid assay. We used gene shuffling and the yeast one-hybrid system to obtain three mutated sequences that can bind to the GCC box. Sequence analysis indicated that two residues, Gly156 in the AP2 domain and Phe62 at the N-terminal domain were mutated to arginine and serine, respectively. Changes of Gly156 to arginine and Phe62 to serine increased the GCCbinding activity of BnaERF-B3-hy15 and the alter of Gly156 to arginine changed the AP2-domain structure of BnaERF-B3- hy15.


Subject(s)
Brassica napus/genetics , Regulatory Elements, Transcriptional , Transcription Factor AP-2/metabolism , Amino Acid Substitution , Base Sequence , Brassica napus/metabolism , Directed Molecular Evolution , Molecular Sequence Data , Mutation , Protein Binding , Protein Structure, Tertiary , Transcription Factor AP-2/genetics , Two-Hybrid System Techniques
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