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1.
Abdom Radiol (NY) ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38831075

ABSTRACT

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

2.
Yi Chuan ; 46(6): 466-477, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38886150

ABSTRACT

Gene knock-in in mammalian cells usually uses homology-directed repair (HDR) mechanism to integrate exogenous DNA template into the target genome site. However, HDR efficiency is often low, and the co-localization of exogenous DNA template and target genome site is one of the key limiting factors. To improve the efficiency of HDR mediated by CRISPR/Cas9 system, our team and previous studies fused different adaptor proteins with SpCas9 protein and expressed them. By using their characteristics of binding to specific DNA sequences, many different CRISPR/SpCas9 donor adapter gene editing systems were constructed. In this study, we used them to knock-in eGFP gene at the 3'-end of the terminal exon of GAPDH and ACTB genes in HEK293T cells to facilitate a comparison and optimization of these systems. We utilized an optimized donor DNA template design method, validated the knock-in accuracy via PCR and Sanger sequencing, and assessed the efficiency using flow cytometry. The results showed that the fusion of yGal4BD, hGal4BD, hLacI, hTHAP11 as well as N57 and other adaptor proteins with the C-terminus of SpCas9 protein had no significant effect on its activity. At the GAPDH site, the donor adapter systems of SpCas9 fused with yGal4BD, hGal4BD, hLacI and hTHAP11 significantly improved the knock-in efficiency. At the ACTB site, SpCas9 fused with yGal4BD and hGal4BD significantly improved the knock-in efficiency. Furthermore, increasing the number of BS in the donor DNA template was beneficial to enhance the knock-in efficiency mediated by SpCas9-hTHAP11 system. In conclusion, this study compares and optimizes multiple CRISPR/Cas9 donor adapter gene editing systems, providing valuable insights for future gene editing applications.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Humans , Gene Editing/methods , HEK293 Cells , Gene Knock-In Techniques/methods , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism
3.
J Am Chem Soc ; 145(16): 8751-8756, 2023 Apr 26.
Article in English | MEDLINE | ID: mdl-36943737

ABSTRACT

This study describes an instantaneously gas-induced dynamic transition of an industrial Cu/ZnO/Al2O3 catalyst. Cu/ZnO clusters become "alive" and lead to a promotion in reaction rate by almost one magnitude, in response to the variation of the reactant components. The promotional changes are functions of either CO2-to-CO or H2O-to-H2 ratio which determines the oxygen chemical potential thus drives Cu/ZnO clusters to undergo reconstruction and allows the maximum formation of Cu-Zn2+ sites for CH3OH synthesis.

4.
ACS Appl Mater Interfaces ; 14(16): 18525-18538, 2022 Apr 27.
Article in English | MEDLINE | ID: mdl-35418231

ABSTRACT

MnO2 polymorphs (α-, ß-, and ε-MnO2) were synthesized, and their chemical/physical properties for CO oxidation were systematically studied using multiple techniques. Density functional theory (DFT) calculations and temperature-programmed experiments reveal that ß-MnO2 shows low energies for oxygen vacancy generation and excellent redox properties, exhibiting significant CO oxidation activity (T90 = 75 °C) and stability even under a humid atmosphere. For the first time, we report that the specific reaction rate for ß-MnO2 (0.135 moleculeCO·nm-2·s-1 at 90 °C) is roughly approximately 4 and 17 times higher than that of ε-MnO2 and α-MnO2, respectively. The specific reaction rate order (ß-MnO2 > ε-MnO2 > α-MnO2) is not only in good agreement with reduction rates (CO-TPSR measurements) but also agrees with the DFT calculation. In combination with in situ spectra and intrinsic kinetic studies, the mechanisms of CO oxidation over various crystal structures of MnO2 were proposed as well. We believe the new insights from this study will largely inspire the design of such a kind of catalyst.

5.
World J Clin Cases ; 9(21): 5812-5821, 2021 Jul 26.
Article in English | MEDLINE | ID: mdl-34368300

ABSTRACT

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss, a functional cure in patients with chronic hepatitis B (CHB) undergoing antiviral therapy, might be an ideal endpoint of antiviral treatment in clinical practice. The factors that contribute to the functional cure remain unclear, and the predictors of functional cure are worth exploring. The concentration and kinetics of soluble programmed death-1 (sPD-1) in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy. AIM: To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels. METHODS: This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing (between 2007 and 2019). All patients were followed up: Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter. Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group. This case group (n = 11) was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls. The Spearman's rank correlation test and receiver operating characteristic curves analysis were performed. RESULTS: The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96, and the differences were significant between the groups at baseline (P = 0.0136), months 6 (P = 0.0003), 12 (P < 0.0001), 24 (P = 0.0007), 48 (P < 0.0001), and 96 (P = 0.0142). After 6 mo of antiviral treatment, the sPD-1 levels were positively correlated with alanine transaminase (ALT) levels (r = 0.5103, P = 0.0017), and the sPD-1 levels showed apparent correlation with ALT (r = 0.6883, P = 0.0192) and HBV DNA (r = 0.5601, P = 0.0703) levels in patients with HBsAg loss. After 12 mo of antiviral treatment, the sPD-1 levels also showed apparent correlation with ALT (r = 0.8134, P = 0.0042) and HBV DNA (r = 0.6832, P = 0.0205) levels in patients with HBsAg loss. The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment, especially at 24 (r = -0.356, P = 0.0497) and 48 (r = -0.4783, P = 0.0037) mo. After 6 mo of antiviral treatment, the AUC of sPD-1 for HBsAg loss was 0.898 (P = 0.000), whereas that of HBsAg was 0.617 (P = 0.419). The cut-off value of sPD-1 was set at 2.34 log pg/mL; the sensitivity and specificity were 100% and 66.7%, respectively. CONCLUSION: The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.

6.
Front Microbiol ; 11: 577266, 2020.
Article in English | MEDLINE | ID: mdl-33101253

ABSTRACT

Higher alcohols such as butanol (C4 alcohol) and hexanol (C6 alcohol) are superior biofuels compared to ethanol. Clostridium carboxidivorans P7 is a typical acetogen capable of producing C4 and C6 alcohols natively. In this study, the composition of trace metals in culture medium was adjusted, and the effects of these adjustments on artificial syngas fermentation by C. carboxidivorans P7 were investigated. Nickel and ferrous ions were essential for growth and metabolite synthesis during syngas fermentation by P7. However, a decreased dose of molybdate improved alcohol fermentation performance by stimulating carbon fixation and solventogenesis. In response to the modified trace metal composition, cells grew to a maximum OD600 nm of 1.6 and accumulated ethanol and butanol to maximum concentrations of 2.0 and 1.0 g/L, respectively, in serum bottles. These yields were ten-fold higher than the yields generated using the original composition of trace metals. Furthermore, 0.5 g/L of hexanol was detected at the end of fermentation. The results from gene expression experiments examining genes related to carbon fixation and organic acid and solvent synthesis pathways revealed a dramatic up-regulation of the Wood-Ljungdahl pathway (WLP) gene cluster, the bcs gene cluster, and a putative CoA transferase and butanol dehydrogenase, thereby indicating that both de novo synthesis and acid re-assimilation contributed to the significantly elevated accumulation of higher alcohols. The bdh35 gene was speculated to be the key target for butanol synthesis during solventogenesis.

7.
ChemSusChem ; 12(17): 3955-3959, 2019 Sep 06.
Article in English | MEDLINE | ID: mdl-31332954

ABSTRACT

Selectively approaching chemicals with one composition-tunable catalyst is attractive for practical manufacturing. Bimetallic copper-indium (Cu-In) catalysts have been synthesized by using a coprecipitation method and found to be among the best reported In-based catalysts for electrochemical CO2 reduction to CO or HCOOH. By varying the metal ratio, the catalyst can be tuned from a core-shell structure that selectively produces CO to a well-mixed structure that prefers HCOOH production. The distinct selectivities depend on the structure-sensitive binding strength of key reactive intermediates. These findings can benefit the development of a broader range of selectivity-tunable catalysts.

8.
Angew Chem Int Ed Engl ; 58(27): 9083-9087, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31074080

ABSTRACT

The commercial high-temperature water-gas shift (HT-WGS) catalyst consists of CuO-Cr2 O3 -Fe2 O3 , where Cu functions as a chemical promoter to increase the catalytic activity, but its promotion mechanism is poorly understood. In this work, a series of iron-based model catalysts were investigated with in situ or pseudo in situ characterization, steady-state WGS reaction, and density function theory (DFT) calculations. For the first time, a strong metal-support interaction (SMSI) between Cu and FeOx was directly observed. During the WGS reaction, a thin FeOx overlayer migrates onto the metallic Cu particles, creating a hybrid surface structure with Cu-FeOx interfaces. The synergistic interaction between Cu and FeOx not only stabilizes the Cu clusters, but also provides new catalytic active sites that facilitate CO adsorption, H2 O dissociation, and WGS reaction. These new fundamental insights can potentially guide the rational design of improved iron-based HT-WGS catalysts.

9.
Front Neurosci ; 13: 445, 2019.
Article in English | MEDLINE | ID: mdl-31143096

ABSTRACT

Background: The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a promising approach that should be explored for more effective clinical options for neurodegenerative disorders. B7C is s synthetic drug that has been studied for over 20 years and represents a promising multi-target drug for the treatment of neurodegenerative disorders, such as AD. Aims: The present systematic review, thus, aims at examining existing studies on the effect of B7C on different molecular targets and at discussing the relevance of B7C in neurological disorders. Methods: A list of predefined search terms was used to retrieve relevant articles from the databases of Embase, Pubmed, Scopus, and Web of Science. The selection of articles was done by two independent authors, who were considering articles concerned primarily with the evaluation of the effect of B7C on neurological disorders. Only full-text articles written in English were included; whereas, systematic reviews, meta-analyses, book chapters, conference subtracts, and computational studies were excluded. Results: A total of 2,266 articles were retrieved out of which 41 articles were included in the present systematic review. The effect of B7C on molecular targets, including AChE, BChE, BACE-1, NMDA receptor, GABA receptor, NOS, and Kv4.2 potassium channels was evaluated. Moreover, the studies that were included assessed the effect of B7C on biological processes, such as apoptosis, neuritogenesis, and amyloid beta aggregation. The animal studies examined in the review focused on the effect of B7C on cognition and memory. Conclusions: The beneficial effects observed on different molecular targets and biological processes relevant to neurological conditions confirm that B7C is a promising multi-target drug with the potential to treat neurological disorders.

10.
J Nanosci Nanotechnol ; 19(6): 3343-3355, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-30744762

ABSTRACT

Pure TiO2 nanoparticles and ones doped with Fe and/or Ni were successfully prepared by a co-precipitation method from ilmenite. The samples were structurally characterized by XRD, XPS, FT-IR, UV-vis, SEM, EDX, AAS and BET measurement. The XRD results showed that all samples were anatase TiO2, and no characteristic peaks of dopants were observed. The crystallite sizes of all doped TiO2 nanoparticles were less than 20 nm and doping TiO2 with metal ions can suppress the crystal growth of the particles. The XRD and XPS results indicated that TiO2 was uniformly doped and its crystalline phase was not changed by doping. The specific surface area of Fe-Ni/TiO2 is bigger than that of the un-doped TiO2. The pore size and pore volume of Fe-Ni/TiO2 is smaller than that of the un-doped. UV-vis spectra of the samples showed that the absorption edge red shifted with increasing doped metal content. The photocatalytic activity was evaluated in oxidative degradation of methylene blue (MB) with H2O2 under visible light irradiation. When doped with a single type of transition metal, the photocatalytic performance of Ni-doped samples was lower than that of Fe-doped ones. For the co-doped catalysts, the catalytic efficiency of 0.5%Fe4%Ni/TiO2 was the highest, reaching 93.34% after 250 min. Metal doping enhanced the photocatalytic decomposition of methylene blue compared with that of pure TiO2 by up to 1.5 times. The synergistic effects of the two metal ions improved the photocatalytic performance. The particles exhibited pronounced activity in degradation of MB as well as efficient recyclability. The photocatalytic degradation mechanism of methylene blue was analyzed.

11.
Angew Chem Int Ed Engl ; 58(20): 6595-6599, 2019 May 13.
Article in English | MEDLINE | ID: mdl-30689279

ABSTRACT

Molecular complexes with inexpensive transition-metal centers have drawn extensive attention, as they show a high selectivity in the electrochemical conversion of CO2 to CO. In this work, we propose a new strategy to covalently graft cobalt porphyrin onto the surface of a carbon nanotube by a substitution reaction at the metal center. Material characterization and electrochemical studies reveal that the porphyrin molecules are well dispersed at a high loading of 10 wt. %. As a result, the turnover frequency for CO formation is improved by a factor of three compared to traditional physically-mixed catalysts with the same cobalt content. This leads to an outstanding overall current density of 25.1 mA cm-2 and a Faradaic efficiency of 98.3 % at 490 mV overpotential with excellent long-term stability. This work provides an effective pathway for the improvement of the performance of electrocatalysts that could inspire rational design of molecular catalysts in the future.

12.
Basic Clin Pharmacol Toxicol ; 123(6): 670-677, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29924913

ABSTRACT

Chemotherapy is one of the most effective forms of cancer treatment. It has been widely used in the treatment of various malignant tumours. To investigate molecular mechanisms responsible for the chemoresistance of anaplastic thyroid cancer (ATC), we established the doxorubicin (Dox) resistance of human ATC SW1736 and 8305C cells and named them SW1736/Dox and 8305C/Dox, respectively. We evaluated the expression of various micro-RNAs (miRNAs) between control and Dox-resistant ATC cells and found that the expression of miR-27b-3p was significantly increased in Dox-resistant ATC cells. Targeted inhibition of miR-27b can increase the sensitivity of SW1736/Dox and 8305C/Dox cells. Bioinformatics analysis revealed that miR-27b can directly target peroxisome proliferator-activated receptor gamma (PPARγ) within the 3' untranslated region (UTR). This was proved by the results that miR-27b-3p down-regulated the protein and mRNA levels of PPARγ. While the mutant in the core binding sites of PPARγ abolished miR-27b-3p-induced down-regulation of luciferase activity. Over-expression of PPARγ can increase the Dox sensitivity of SW1736/Dox and 8305C/Dox cells. Basic fibroblast growth factor (bFGF) might be involved in miR-27b-3p/PPARγ-regulated Dox resistance of ATC cells. The activation of p65 nuclear factor-κB (NF-κB) regulated the up-regulation of miR-27b-3p in Dox-resistant ATC cells. Collectively, our data revealed that miR-27b-3p/PPARγ is involved in the Dox resistance of human ATC cells. It suggested that targeted inhibition of miR-27b-3p might be helpful to overcome the drug resistance of ATC cells.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , MicroRNAs/physiology , PPAR gamma/drug effects , Thyroid Carcinoma, Anaplastic/diet therapy , Thyroid Neoplasms/drug therapy , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Humans , MicroRNAs/genetics , PPAR gamma/metabolism , Real-Time Polymerase Chain Reaction , Up-Regulation/drug effects , Wetlands
13.
Sci Rep ; 8(1): 3193, 2018 02 16.
Article in English | MEDLINE | ID: mdl-29453457

ABSTRACT

We study unextendible maximally entangled bases (UMEBs) in [Formula: see text] (d < d'). An operational method to construct UMEBs containing d(d' - 1) maximally entangled vectors is established, and two UMEBs in [Formula: see text] and [Formula: see text] are given as examples. Furthermore, a systematic way of constructing UMEBs containing d(d' - r) maximally entangled vectors in [Formula: see text] is presented for r = 1, 2, …, d - 1. Correspondingly, two UMEBs in [Formula: see text] are obtained.

14.
Antonie Van Leeuwenhoek ; 111(4): 485-491, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29134394

ABSTRACT

A Gram-stain negative, aerobic, motile and ovoid- to rod-shaped bacteria strain, designated XC0140T, was isolated from soil samples near the sewage treatment tank of a chemical factory in Zhejiang Province, China, and subjected to polyphasic taxonomic investigation. Strain XC0140T grew at 10-37 °C and pH 6.0-9.0 (optimum, 35 °C and pH 7.5) and with 0-17% (w/v) NaCl (optimum, 1%). According to phylogenetic analysis based on 16S rRNA gene sequences, strain XC0140T was assigned to the genus Pararhizobium with high 16S rRNA gene sequence similarity of 95.97% to "Pararhizobium helanshanense CCNWQTX14T", followed by Pararhizobium sphaerophysae CCNWGS0238T (95.95%). Chemotaxonomic analysis showed that strain XC0140T contains ubiquinone-10 as the predominant respiratory quinone and possessed summed feature 8 (comprising C18: 1 ω7c and/or ω6c), 11-methyl C18:1 ω7c, C18: 0 and C16: 0 as predominant forms of fatty acids. The polar lipids of strain XC0140T consisted of seven phospholipids (PL), two aminolipids (AL), one glycolipid (GL) and three unidentified lipids (L1, L2 and L3). The DNA G+C content was 62.7 mol%. Based on the polyphasic taxonomic characterization, strain XC0140T is considered to represent a novel species of the genus Pararhizobium, for which the name Pararhizobium haloflavum sp. nov. is proposed. (type strain XC0140T = MCCC 1K03228T = KCTC 52582T).


Subject(s)
Phylogeny , Rhizobiaceae/classification , Soil Microbiology , Aerobiosis , Base Composition , China , Fatty Acids/analysis , Genes, Bacterial/genetics , Genome, Bacterial/genetics , Glycolipids/analysis , Hydrogen-Ion Concentration , Phospholipids/analysis , RNA, Ribosomal, 16S/genetics , Rhizobiaceae/chemistry , Rhizobiaceae/genetics , Sewage/microbiology , Sodium Chloride , Species Specificity , Ubiquinone
15.
Oncol Rep ; 38(5): 3085-3093, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28901486

ABSTRACT

The function of miRNA­148a in lymphatic metastases of papillary thyroid cancer and its mechanism were tested. In this investigation, miRNA­148a expression of lymphatic metastases of papillary thyroid cancer patients was inhibited, compared with normal group. We found that miRNA­148a overexpression was effectively reduced cell cell proliferation and metastases, and induced apoptosis of papillary thyroid cancer in vitro. Overexpression of miRNA­148a significantly induced Bax protein expression and caspase­3/9 levels, and suppressed phosphorylation STAT3 (p­STAT3), PI3K and p­Akt protein expression of papillary thyroid cancer in vitro. Next, si­STAT3, could inhibit p­STAT3 protein expression, reducing cell-cell proliferation and metastases, and inducing apoptosis of papillary thyroid cancer following miRNA­148a overexpression. Then, the PI3K inhibitor was able to inhibit PI3K and p­Akt protein expression, reduced cell cell proliferation and metastases, and induced apoptosis of papillary thyroid cancer following miRNA­148a overexpression. Taken together, our results suggest that miRNA­148a inhibits lymphatic metastases of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways.


Subject(s)
Carcinoma, Papillary/genetics , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , STAT3 Transcription Factor/genetics , Thyroid Neoplasms/genetics , Carcinoma, Papillary/metabolism , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Humans , Lymphatic Metastasis , Phosphorylation , STAT3 Transcription Factor/metabolism , Signal Transduction , Thyroid Cancer, Papillary , Thyroid Neoplasms/metabolism
16.
ChemSusChem ; 10(17): 3342-3346, 2017 09 11.
Article in English | MEDLINE | ID: mdl-28752581

ABSTRACT

Highly selective hydrogen peroxide (H2 O2 ) synthesis directly from H2 and O2 is a strongly desired reaction for green processes. Herein a highly efficient palladium-tellurium (Pd-Te/TiO2 ) catalyst with a selectivity of nearly 100 % toward H2 O2 under mild conditions (283 K, 0.1 MPa, and a semi-batch continuous flow reactor) is reported. The size of Pd particles was remarkably reduced from 2.1 nm to 1.4 nm with the addition of Te. The Te-modified Pd surface could significantly weaken the dissociative activation of O2 , leading to the non-dissociative hydrogenation of O2 . Density functional theory calculations illuminated the critical role of Te in the selective hydrogenation of O2 , in that the active sites composed of Pd and Te could significantly restrain side reactions. This work has made significant progress on the development of high-selectivity catalysts for the direct synthesis of H2 O2 at ambient pressure.


Subject(s)
Hydrogen Peroxide/chemistry , Hydrogen Peroxide/chemical synthesis , Palladium/chemistry , Pressure , Tellurium/chemistry , Catalysis , Chemistry Techniques, Synthetic , Models, Molecular , Molecular Conformation
17.
Neural Regen Res ; 11(8): 1339-46, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27651784

ABSTRACT

Rasagiline, a monoamine oxidase-B inhibitor, and bis(propyl)-cognitin (B3C), a novel dimer are reported to be neuroprotective. Herein, the synergistical neuroprotection produced by rasagiline and B3C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice of Parkinsonism. By using neurobehavioural tests, high-performance liquid chromatography and western blot assay, we showed that B3C at 0.3 mg/kg, rasagiline at 0.02 mg/kg, as well as co-treatment with B3C and rasagiline prevented MPTP-induced behavioural abnormities, increased the concentrations of dopamine and its metabolites in the striatum, and up-regulated the expression of tyrosine hydroxylase in the substantia nigra. However, the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3C or rasagiline alone. Collectively, we have demonstrated that B3C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.

18.
Neurochem Res ; 41(9): 2267-77, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27161377

ABSTRACT

Oxidative stress mediates the pathogenesis of neurodegenerative disorders. Gartanin, a natural xanthone of mangosteen, possesses multipharmacological activities. Herein, the neuroprotection capacity of gartanin against glutamate-induced damage in HT22 cells and its possible mechanism(s) were investigated for the first time. Glutamate resulted in cell death in a dose-dependent manner and supplementation of 1-10 µM gartanin prevented the detrimental effects of glutamate on cell survival. Additional investigations on the underlying mechanisms suggested that gartanin could effectively reduce glutamate-induced intracellular ROS generation and mitochondrial depolarization. We further found that gartanin induced HO-1 expression independent of nuclear factor erythroid-derived 2-like 2 (Nrf2). Subsequent studies revealed that the inhibitory effects of gartanin on glutamate-induced apoptosis were partially blocked by small interfering RNA-mediated knockdown of HO-1. Finally, the protein expression of phosphorylation of AMP-activated protein kinase (AMPK) and its downstream signal molecules, Sirtuin activator (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), increased after gartanin treatment. Taken together, these findings suggest gartanin is a potential neuroprotective agent against glutamate-induced oxidative injury partially through increasing Nrf-2-independed HO-1 and AMPK/SIRT1/PGC-1α signaling pathways.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Apoptosis/drug effects , Heme Oxygenase-1/metabolism , Membrane Proteins/metabolism , NF-E2-Related Factor 2/metabolism , Neurons/drug effects , Xanthones/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Glutamic Acid/pharmacology , Mice , Neurons/cytology , Neurons/metabolism , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Xanthones/chemistry
19.
Neurochem Res ; 41(7): 1806-17, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27038926

ABSTRACT

Natural xanthones have diversity pharmacological activities. Here, a series of xanthones isolated from the pericarps of Garcinia mangostana Linn, named α-Mangostin, 8-Deoxygartanin, Gartanin, Garciniafuran, Garcinone C, Garcinone D, and γ-Mangostin were investigated. Biological screening performed in vitro and in Escherichia coli cells indicated that most of the xanthones exhibited significant inhibition of self-induced ß-amyloid (Aß) aggregation and also ß-site amyloid precursor protein-cleaving enzyme 1, acted as potential antioxidants and biometal chelators. Among these compounds, α-Mangostin, Gartanin, Garcinone C and γ-Mangostin showed better antioxidant properties to scavenge Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) free radical than Trolox, and potent neuroprotective effects against glutamate-induced HT22 cell death partly by up-regulating HO-1 protein level and then scavenging reactive oxygen species. Moreover, Gartanin, Garcinone C and γ-Mangostin could be able to penetrate the blood-brain barrier (BBB) in vitro. These findings suggest that the natural xanthones have multifunctional activities against Alzheimer's disease (AD) and could be promising compounds for the therapy of AD.


Subject(s)
Alzheimer Disease/metabolism , Garcinia mangostana , Plant Extracts/therapeutic use , Xanthones/therapeutic use , Alzheimer Disease/drug therapy , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Animals , Aspartic Acid Endopeptidases/antagonists & inhibitors , Aspartic Acid Endopeptidases/metabolism , Cell Line , Mice , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Xanthones/isolation & purification , Xanthones/pharmacology
20.
J Hazard Mater ; 305: 178-189, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26685065

ABSTRACT

An advanced method for the degradation of trichloroethylene (TCE) over Pd/MCM-41 catalysts through a hydrogen-transfer was investigated. Formic acid (FA) was used instead of gaseous H2 as the hydrogen resource. As a model H-carrier compound, FA has proven to yield less by-products and second-hand pollution during the reaction. Several factors have been studied, including: the property of catalyst supports, Pd loading and size, temperature, initial concentrations of FA and TCE (potential impact on the reaction rates of TCE degradation), and FA decomposition. The intrinsic kinetics for TCE degradation were measured, while the apparent activation energies and the reaction orders with respect to TCE and FA were calculated through power law models. On the basis of kinetics, we assumed a plausible reaction pathway for TCE degradation in which the catalytic degradation of TCE is most likely the rate-determining step for this reaction.

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