Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 57
Filter
1.
J Enzyme Inhib Med Chem ; 38(1): 2193866, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37013838

ABSTRACT

Inositol polyphosphates (IPs) are a group of inositol metabolites that act as secondary messengers for external signalling cues. They play various physiological roles such as insulin release, telomere length maintenance, cell metabolism, and aging. Inositol hexakisphosphate kinase 2 (IP6K2) is a key enzyme that produces 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-IP7), which influences the early stages of glucose-induced exocytosis. Therefore, regulation of IP6Ks may serve as a promising strategy for treating diseases such as diabetes and obesity. In this study, we designed, synthesised, and evaluated flavonoid-based compounds as new inhibitors of IP6K2. Structure-activity relationship studies identified compound 20s as the most potent IP6K2 inhibitor with an IC50 value of 0.55 µM, making it 5-fold more potent than quercetin, the reported flavonoid-based IP6K2 inhibitor. Compound 20s showed higher inhibitory potency against IP6K2 than IP6K1 and IP6K3. Compound 20s can be utilised as a hit compound for further structural modifications of IP6K2 inhibitors.


Subject(s)
Enzyme Inhibitors , Flavonoids , Insulin , Phosphotransferases (Phosphate Group Acceptor) , Flavonoids/pharmacology , Inositol , Signal Transduction , Phosphotransferases (Phosphate Group Acceptor)/antagonists & inhibitors , Enzyme Inhibitors/pharmacology
2.
Aging (Albany NY) ; 14(2): 678-707, 2022 01 30.
Article in English | MEDLINE | ID: mdl-35093936

ABSTRACT

Senescence is a distinct set of changes in the senescence-associated secretory phenotype (SASP) and leads to aging and age-related diseases. Here, we screened compounds that could ameliorate senescence and identified an oxazoloquinoline analog (KB1541) designed to inhibit IL-33 signaling pathway. To elucidate the mechanism of action of KB1541, the proteins binding to KB1541 were investigated, and an interaction between KB1541 and 14-3-3ζ protein was found. Specifically, KB1541 interacted with 14-3-3ζ protein and phosphorylated of 14-3-3ζ protein at serine 58 residue. This phosphorylation increased ATP synthase 5 alpha/beta dimerization, which in turn promoted ATP production through increased oxidative phosphorylation (OXPHOS) efficiency. Then, the increased OXPHOS efficiency induced the recovery of mitochondrial function, coupled with senescence alleviation. Taken together, our results demonstrate a mechanism by which senescence is regulated by ATP synthase 5 alpha/beta dimerization upon fine-tuning of KB1541-mediated 14-3-3ζ protein activity.


Subject(s)
14-3-3 Proteins , Oxidative Phosphorylation , 14-3-3 Proteins/genetics , Adenosine Triphosphate/metabolism , Cellular Senescence , Dimerization , Protein Binding
3.
Bioorg Chem ; 104: 104304, 2020 11.
Article in English | MEDLINE | ID: mdl-33011530

ABSTRACT

Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, is considered an excellent target for the diagnosis or treatment of prostate cancer. We previously investigated the effect of ß- and γ-amino acids with (S)- or (R)-configuration in the S1 pocket on the binding affinity for PSMA. However, comprehensive studies on the effect of α-amino acid with (R)-configuration in the S1' pocket has not been reported yet. We selected ZJ-43 (1) and DCIBzL (5) as templates and synthesized their analogues with (S)- or (R)-configuration in the P1 and P1' regions. The PSMA-inhibitory activities of compounds with altered chirality in the P1' region were dropped dramatically, with their IC50 values changing from nM to µM ranges. The compounds with (S)-configuration at both P1 and P1' regions were more potent than the others. The findings of this study may provide insights regarding the structural modification of PSMA inhibitor in the S1' binding pocket.


Subject(s)
Amino Acids/pharmacology , Glutamate Carboxypeptidase II/antagonists & inhibitors , Peptides/pharmacology , Amino Acids/chemical synthesis , Amino Acids/chemistry , Antigens, Surface/metabolism , Dose-Response Relationship, Drug , Glutamate Carboxypeptidase II/metabolism , Humans , Ligands , Molecular Structure , Peptides/chemical synthesis , Peptides/chemistry , Stereoisomerism , Structure-Activity Relationship
4.
J Med Chem ; 63(6): 3261-3273, 2020 03 26.
Article in English | MEDLINE | ID: mdl-32097010

ABSTRACT

Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are α-(l)-amino acids. In this study, we aimed to determine the effect of ß- and γ-amino acids in the S1 pocket on the binding affinity for PSMA. We synthesized and evaluated the ß- and γ-amino acid analogues with (S)- or (R)-configuration with keeping α-(l)-Glu as the S1'-binding pharmacophore. The structure-activity relationship studies identified that compound 13c, a ß-amino acid analogue with (R)-configuration, exhibited the most potent PSMA inhibitory activity with an IC50 value of 3.97 nM. The X-ray crystal structure of PSMA in complex with 13c provided a mechanistic basis for the stereochemical preference of PSMA, which can guide the development of future PSMA inhibitors.


Subject(s)
Amino Acids/chemistry , Glutamate Carboxypeptidase II/antagonists & inhibitors , Urea/analogs & derivatives , Amino Acids/chemical synthesis , Amino Acids/metabolism , Antigens, Surface/metabolism , Cell Line, Tumor , Glutamate Carboxypeptidase II/metabolism , Humans , Molecular Structure , Protein Binding , Structure-Activity Relationship , Urea/chemical synthesis , Urea/metabolism
6.
Bioorg Med Chem Lett ; 30(3): 126894, 2020 02 01.
Article in English | MEDLINE | ID: mdl-31874825

ABSTRACT

Prostate-specific membrane antigen (PSMA) is a zinc-bound metalloprotease which is highly expressed in metastatic prostate cancer. It has been considered an excellent target protein for prostate cancer imaging and targeted therapy because it is a membrane protein and its active site is located in the extracellular region. We successfully synthesized and evaluated a novel PSMA ligand conjugated with BODIPY650/665. Compound 1 showed strong PSMA-inhibitory activity and selective uptake into PSMA-expressing tumors. Compound 1 has the potential to be utilized as a near infrared (NIR) optical imaging probe targeting PSMA-expressing cancers.


Subject(s)
Boron Compounds/chemistry , Drug Design , Fluorescent Dyes/chemical synthesis , Glutamate Carboxypeptidase II/antagonists & inhibitors , Animals , Antigens, Surface/metabolism , Binding Sites , Cell Line, Tumor , Fluorescent Dyes/chemistry , Glutamate Carboxypeptidase II/metabolism , Humans , Ligands , Male , Mice , Molecular Dynamics Simulation , Optical Imaging , Polyethylene Glycols/chemistry , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Transplantation, Heterologous
7.
Sci Rep ; 9(1): 8762, 2019 06 19.
Article in English | MEDLINE | ID: mdl-31217492

ABSTRACT

Thymic stromal lymphopoietin (TSLP) plays an important role in the differentiation and proliferation of Th2 cells, resulting in eosinophilic inflammation and numerous allergic diseases. Baicalein (1), a major component of Scutellaria baicalensis, was found to be the first small molecule to block TSLP signaling pathways. It inhibited effectively eosinophil infiltration in house dust mite-induced and ovalbumin-challenged mouse models. Structure-activity relationship studies identified compound 11a, a biphenyl flavanone analog, as a novel human TSLP inhibitor for the discovery and development of new anti-allergic drugs.


Subject(s)
Anti-Allergic Agents , Asthma , Cytokines , Flavanones , Animals , Anti-Allergic Agents/chemical synthesis , Anti-Allergic Agents/chemistry , Anti-Allergic Agents/pharmacology , Asthma/chemically induced , Asthma/drug therapy , Asthma/immunology , Asthma/pathology , Cell Line , Cytokines/antagonists & inhibitors , Cytokines/chemistry , Flavanones/chemical synthesis , Flavanones/chemistry , Flavanones/pharmacology , Humans , Mice , Pyroglyphidae/immunology
8.
Bioorg Chem ; 89: 102990, 2019 08.
Article in English | MEDLINE | ID: mdl-31136899

ABSTRACT

Hepsin is a type II serine protease that is highly expressed in neoplastic prostate. It is an attractive biomarker for imaging metastatic prostate cancer because of its overexpression in advanced prostate cancer and the location of its active site on the cell surface. We designed and synthesized novel hepsin-targeted imaging probes by conjugating the hepsin-binding ligand with near-infrared (NIR) optical dyes. The Leu-Arg dipeptides, attached to BODIPY or SulfoCy7, exhibited strong hepsin-inhibitory activities with Ki values of 21 and 22 nM, respectively. Compound 2 showed selective uptake and retention in hepsin-overexpressing cells. This is the first report of hepsin-targeted optical probes with strong binding affinities and high selectivity over matriptase. Compound 2 has the potential to be used for developing hepsin-based imaging probes and be as a prototype molecule in the design of new hepsin inhibitors.


Subject(s)
Drug Design , Fluorescent Dyes/chemistry , Serine Endopeptidases/chemistry , Serine Proteinase Inhibitors/chemistry , Binding Sites , Boron Compounds/chemistry , Catalytic Domain , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Ligands , Molecular Docking Simulation , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Serine Proteinase Inhibitors/metabolism
9.
Theranostics ; 7(7): 1835-1846, 2017.
Article in English | MEDLINE | ID: mdl-28638471

ABSTRACT

Currently, the point of care testing (POCT) is not fully developed for subtype-specific avian influenza virus detection. In this study, an H5N1 hemaglutinin 1 (HA1) epitope (P0: KPNDAINF) and three modified peptides (P1: KPNTAINF, P2: KPNGAINF, P3: KPNDAINDAINF) were evaluated as POCT elements for rapid detection of avian influenza virus. Based on modeling predictions by Autodock Vina, binding affinity varied depending on alteration of one amino acid in these peptides. The binding energy of P2 indicated its potential for a strong interaction with HA. Fluorescence-linked immunosorbent assay experimentally demonstrated the interaction between these peptides and virus. The four peptides interacted with HA1 of H5N3 with different binding affinities with P2 showing the strongest binding affinity. When P0 and P2 peptides were used in rapid fluorescent immunochromatographic test (FICT) as detection elements, the inter-assay coefficients of variation (CV) indicated that P2-linked FICT was more acceptable than the P0-linked FICT in the presence of human specimens. Antibody pair-linked FICT was influenced by clinical samples more than the P2-linked FICT assay, which showed a 4-fold improvement in the detection limit of H5N3 and maintained H5 subtype-specificity. Compared to the rapid diagnostic test (RDT) which is not specific for influenza subtypes, P2-linked FICT could increase virus detection. In conclusion, results of this study suggest that HA epitope-derived peptides can be used as alternatives to antibodies for a rapid fluorescent diagnostic assay to detect avian influenza virus.


Subject(s)
Chromatography, Affinity/methods , Diagnostic Tests, Routine/methods , Influenza in Birds/diagnosis , Orthomyxoviridae/isolation & purification , Animals , Birds , Epitopes/immunology , Influenza in Birds/virology , Orthomyxoviridae/immunology , Peptides/metabolism , Protein Binding , Staining and Labeling/methods , Time Factors
10.
Biosens Bioelectron ; 94: 677-685, 2017 Aug 15.
Article in English | MEDLINE | ID: mdl-28390319

ABSTRACT

Sensitive and rapid diagnostic systems for avian influenza (AI) virus are required to screen large numbers of samples during a disease outbreak and to prevent the spread of infection. In this study, we employed a novel fluorescent dye for the rapid and sensitive recognition of AI virus. The styrylpyridine phosphor derivative was synthesized by adding allyl bromide as a stable linker and covalently immobilizing it on latex beads with antibodies generating the unique Red dye 53-based fluorescent probe. The performance of the innovative rapid fluorescent immnunochromatographic test (FICT) employing Red dye 53 in detecting the AI virus (A/H5N3) was 4-fold and 16-fold higher than that of Europium-based FICT and the rapid diagnostic test (RDT), respectively. In clinical studies, the presence of human nasopharyngeal specimens did not alter the performance of Red dye 53-linked FICT for the detection of H7N1 virus. Furthermore, in influenza A virus-infected human nasopharyngeal specimens, the sensitivity of the Red dye 53-based assay and RDT was 88.89% (8/9) and 55.56% (5/9) relative to rRT-PCR, respectively. The photostability of Red dye 53 was higher than that of fluorescein isothiocyanate (FITC), showing a stronger fluorescent signal persisting up to 8min under UV. The Red dye 53 could therefore be a potential probe for rapid fluorescent diagnostic systems that can recognize AI virus in clinical specimens.


Subject(s)
Biosensing Techniques/methods , Influenza A Virus, H7N1 Subtype/isolation & purification , Influenza A virus/isolation & purification , Influenza in Birds/diagnosis , Influenza, Human/diagnosis , Animals , Chickens , Disease Outbreaks , Fluorescent Dyes , Humans , Influenza A Virus, H7N1 Subtype/pathogenicity , Influenza A virus/pathogenicity , Influenza in Birds/virology , Influenza, Human/virology , Sensitivity and Specificity
11.
Proteomics ; 17(6)2017 03.
Article in English | MEDLINE | ID: mdl-28133907

ABSTRACT

Current diagnostic markers for gastric cancer are not sufficiently specific or sensitive for use in clinical practice. The aims of this study are to compare the proteomes of serum samples from patients with gastric cancers and normal controls, and to develop useful tumor markers of gastric cancer by quantitative proteomic analysis. We identified a total of 388 proteins with a ≤1% FDR and with at least two unique peptides from the sera of each group. Among them, 215, 251, and 260 proteins were identified in serum samples of patients in an advanced cancer group, early cancer group, and normal control group, respectively. We selected differentially expressed proteins in cancer patients compared with those of normal controls via semiquantitative analyses comparing the spectral counts of identified proteins. These differentially expressed proteins were successfully verified using an MS-based quantitative assay, multiple reactions monitoring analysis. Four proteins (vitronectin, clusterin isoform 1, thrombospondin 1, and tyrosine-protein kinase SRMS) were shown to have significant changes between the cancer groups and the normal control group. These four serum proteins were able to discriminate gastric cancer patients from normal controls with sufficient specificity and selectivity.


Subject(s)
Biomarkers, Tumor/blood , Proteomics/methods , Stomach Neoplasms/blood , Stomach Neoplasms/diagnosis , Adult , Area Under Curve , Case-Control Studies , Female , Gene Ontology , Humans , Male , Middle Aged , ROC Curve , Reproducibility of Results , Statistics as Topic
12.
J Nanosci Nanotechnol ; 15(7): 5224-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26373111

ABSTRACT

In this work, ZnS microspheres consisting of nanoblocks were synthesized by a simple, template-free approach employing a hydrothermal reaction at different temperatures, using Zn(CH3COO)2 and Na2S2O3 · 5H2O as starting materials in the aqueous solution. The synthesized samples were characterized using field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET). The photocatalysts were evaluated using photodecomposition of methylene blue under UV-C light. The photocatalytic degradation rate followed a pseudo-first-order equation. The kinetic constant (k1) of the ZnS microspheres was 5.43 x 10(-2) min(-1).

13.
J Nanosci Nanotechnol ; 15(1): 192-5, 2015 Jan.
Article in English | MEDLINE | ID: mdl-26328328

ABSTRACT

Polycaprolactone (PCL) nanofibers (PCL-NF) with uniform fibrous structure were fabricated by electrospinning. However, PCL-NF has hydrophobic surface, lacks functional groups and hence it is not a good substrate for cell adhesion. To improve the cell adhesion, PCL-NF surfaces were modified by low pressure RF discharge plasma treatment using monomer such as acrylic acid or oxygen gas. The plasma treated PCL-NFs improved the wettability and cell proliferation.


Subject(s)
Bone Substitutes/chemistry , Nanofibers/chemistry , Polyesters/chemistry , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Mice , Osteoblasts/drug effects , Plasma Gases , Polyesters/pharmacology
14.
J Nanosci Nanotechnol ; 15(8): 5653-5, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26369132

ABSTRACT

Polycaprolactone (PCL)/TiO2 composite films (PTCFs) were prepared by a solvent casting method at various concentrations of TiO2 (1, 3, 5, and 10 wt%) and then treated using oxygen plasma. The hydrophilicity of the oxygen plasma treated PTCFs increased as the treatment time was increased, due to the oxygen induced production of polar species at the surface of the PTCFs. In vitro bioactivities of the composite films were examined by immersion in simulated body fluid for up to 7 days. It was found that the oxygen plasma treatment significantly influenced the in vitro bioactivity of the PTCFs.


Subject(s)
Calcium Phosphates/chemical synthesis , Coated Materials, Biocompatible/chemical synthesis , Nanocomposites/chemistry , Oxygen/chemistry , Polyesters/chemistry , Titanium/chemistry , Biomimetic Materials/chemistry , Body Fluids/chemistry , Materials Testing , Nanocomposites/ultrastructure , Particle Size , Plasma Gases/chemistry , Surface Properties
15.
Biochim Biophys Acta ; 1854(5): 356-64, 2015 May.
Article in English | MEDLINE | ID: mdl-25641559

ABSTRACT

Spinocerebellar ataxia type 1 (SCA1), an autosomal-dominant neurodegenerative disorder, is caused by expansion of the polyglutamine tract within ataxin-1 (ATXN1). The AXH domain of ATXN1 can mediate neurodegeneration through its interaction with other proteins. We have previously showed that the ubiquitin-conjugating enzyme UbcH6 modulates the transcriptional repression activity of ATXN1 through ubiquitylation. In the present study, we sought to identify sites in the AXH domain that are ubiquitylated by UbcH6. Systematic replacement of each lysine residue in the AXH domain revealed that the lysine at 589 (K589) of ATXN1 is essential for its ubiquitylation by UbcH6. Mass spectrometry studies further confirmed the ubiquitylation site. Interestingly, protein aggregation was significantly enhanced in mutant AXH K589R, implying that the aggregation is strongly associated with the level of ATXN1 expression. Our study may suggest a therapeutic potential of UbcH6 in the treatment of SCA1.


Subject(s)
Lysine , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/metabolism , Nuclear Proteins/chemistry , Nuclear Proteins/metabolism , Ubiquitination , Amino Acid Sequence , Ataxin-1 , Ataxins , Binding Sites/genetics , HEK293 Cells , Humans , Lysine/chemistry , Lysine/genetics , Models, Molecular , Mutagenesis, Site-Directed , Mutant Proteins/chemistry , Mutant Proteins/metabolism , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Protein Aggregates , Protein Binding , Protein Structure, Tertiary/genetics , Ubiquitin-Conjugating Enzymes/metabolism , Ubiquitination/genetics
16.
Proteomics ; 15(2-3): 580-90, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25204828

ABSTRACT

Protein tyrosine nitration (PTN) is a PTM that regulates signal transduction and inflammatory responses, and is related to neurodegenerative and cardiovascular diseases. The cellular function of PTN remains unclear because the low stoichiometry of PTN limits the identification and quantification of nitrated peptides. Effective enrichment is an important aspect of PTN analysis. In this study, we analyzed the in vivo nitroproteome elicited by mating signal transduction in Saccharomyces cerevisiae using a novel chemical enrichment method followed by LC-MS/MS. Nitroproteome profiling successfully identified changes in the nitration states of 14 proteins during mating signal transduction in S. cerevisiae, making this the first reported in vivo nitroproteome in yeast. We investigated the biological functions of these nitroproteins and their relationships to mating signal transduction in S. cerevisiae using a protein-protein interaction network. Our results suggest that PTN and denitration may be involved in nonreactive nitrogen species-mediated signal transduction and can provide clues for understanding the functional roles of PTN in vivo.


Subject(s)
Nitrates/analysis , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Tyrosine/analysis , Amino Acid Sequence , Models, Molecular , Molecular Sequence Data , Nitrates/metabolism , Protein Interaction Maps , Protein Processing, Post-Translational , Proteomics , Saccharomyces cerevisiae/chemistry , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae Proteins/chemistry , Signal Transduction , Tandem Mass Spectrometry , Tyrosine/metabolism
17.
Proteomics ; 15(4): 824-35, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25404199

ABSTRACT

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib are one of gold standard treatment options for nonsmall-cell lung cancer (NSCLC) patients, which eventually fail due to the acquired resistance and relapse because of the development of secondary activating mutations such as T790M in EGFR. Predicting chemo-responsiveness of cancer patients provides a major challenge in chemotherapy. The goal of the present study is to determine whether phospholipid signatures of tumor extracellular vesicles (EV) are associated with gefitinib-resistance of NSCLC. A sophisticated MS-based shotgun lipidomic assays were performed for in-depth analysis of the lipidomes of gefitinib-resistant (PC9R) and responsive (PC9) NSCLC cells and their shed EV from these cell lines (PC9EV or PC9REV). Lipid MALDI-MS analysis showed that EV phospholipid composition was significantly distinct in PC9R, compared to PC9 cells. Following statistical analyses has identified 35 (20 positive and 15 negative ion mode) differentially regulated lipids, which are significantly over- or underexpressed in PC9R EV, compared to PC9 EV (p value < 0.01, fold change > 1.5). Our phospholipid signatures suggest that EV associates with drug sensitivity, which is worthy of additional investigation to assess chemoresistance in patients with NSCLC treated with anti-EGFR TKIs.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung , Cell Extracts , Drug Resistance, Neoplasm , Extracellular Space , Phospholipids , Quinazolines/pharmacology , Cell Extracts/chemistry , Cell Extracts/pharmacology , Cell Line, Tumor , Cytoplasmic Vesicles/chemistry , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/physiology , Extracellular Space/drug effects , Extracellular Space/physiology , Gefitinib , Humans , Phospholipids/pharmacology , Phospholipids/physiology
18.
Phytother Res ; 29(1): 30-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25230217

ABSTRACT

Jasin-hwan-gagambang (BHH10), a modified prescription of Jasin-hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)-induced rats. Sprague-Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17ß-estradiol (E2). BHH10 treatment significantly inhibited OVX-induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C-telopeptide type 1 collagen, and bone morphogenetic protein-2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10-treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN-treated or E2-treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity.


Subject(s)
Bone Density/drug effects , Osteogenesis/drug effects , Osteoporosis/drug therapy , Plant Extracts/pharmacology , Alendronate/pharmacology , Animals , Astragalus propinquus/chemistry , Body Weight , Bone Resorption/prevention & control , Cinnamomum aromaticum/chemistry , Disease Models, Animal , Estradiol/pharmacology , Female , Femur/drug effects , Organ Size , Osteocalcin/blood , Ovariectomy , Phellodendron/chemistry , Rats , Rats, Sprague-Dawley , Toxicity Tests, Acute , Toxicity Tests, Chronic
19.
BMJ Open ; 4(12): e006750, 2014 Dec 23.
Article in English | MEDLINE | ID: mdl-25537788

ABSTRACT

INTRODUCTION: This review aims to evaluate the effectiveness and safety of acupuncture for patients with postoperative pain after laparoscopic surgery. METHODS AND ANALYSIS: We will search the following databases from their inception to October 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), three Chinese databases (China National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and the Wanfang database), one Japanese database (Japan Science and Technology Information Aggregator, Electronic (J-STAGE)) and eight Korean databases (Korean Association of Medical Journal Edition, Korean Medical Database, Korean Studies Information Service System, National Discovery for Science Leaders, Database Periodical Information Academic, Korean National Assembly Digital Library, Oriental Medicine Advanced Searching Integrated System and Korean Traditional Knowledge Portal). All randomised controlled trials of acupuncture for postoperative pain after laparoscopic surgery will be considered for inclusion. The risk of bias and reporting quality will be assessed using the Cochrane risk of bias tool, the Consolidated Standards of Reporting Trials (CONSORT) and the revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The risk ratio for dichotomous data and mean difference or standard mean difference for continuous data will be calculated with 95% CIs. DISSEMINATION: The results of this review will be disseminated through peer-reviewed publication or conference presentation. Our findings will summarise the current evidence of acupuncture to treat postoperative pain after laparoscopic surgery, and may provide important guidance for acupuncture usage after laparoscopic surgery for clinicians and patients. TRIAL REGISTRATION NUMBER: PROSPERO 2014: CRD42014010825.


Subject(s)
Acupuncture Therapy , Laparoscopy/adverse effects , Pain, Postoperative/therapy , Humans , Pain, Postoperative/etiology , Systematic Reviews as Topic
20.
J Nat Prod ; 77(11): 2423-31, 2014 Nov 26.
Article in English | MEDLINE | ID: mdl-25397676

ABSTRACT

Formononetin (1), a plant-derived phytoestrogen, possesses bone protective properties. To address the potential therapeutic efficacy and mechanism of action of 1, we investigated its antiosteoclastogenic activity and its effect on nuclear factor-kappaB ligand (RANKL)-induced bone-marrow-derived macrophages (BMMs). Compound 1 markedly inhibited RANKL-induced osteoclast differentiation in the absence of cytotoxicity, by regulating the expression of osteoprotegerin (OPG) and RANKL in BMMs and in cocultured osteoblasts. Compound 1 significantly inhibited RANKL-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) in a concentration-dependent manner. These effects were accompanied by a decrease in RANKL-induced activation of the NF-κB p65 subunit, degradation of inhibitor κBα (IκBα), induction of NF-κB, and phosphorylation of AKT, extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). NF-κB siRNA suppressed AKT, ERK, JNK, and p38 MAPK phosphorylation. Furthermore, 1 significantly suppressed c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), key transcription factors during osteoclastogenesis. SP600125, a specific inhibitor of JNK, reduced RANKL-induced expression of phospho-c-Jun, c-Fos, and NFATc1 and inhibited osteoclast formation. These results suggested that 1 acted as an antiresorption agent by blocking osteoclast activation.


Subject(s)
Isoflavones/pharmacology , NF-kappa B/antagonists & inhibitors , Phytoestrogens/pharmacology , Chemokine CCL2 , Interleukin-6/metabolism , Isoflavones/chemistry , JNK Mitogen-Activated Protein Kinases/metabolism , Macrophages/drug effects , Mitogen-Activated Protein Kinases/metabolism , Molecular Structure , Osteoblasts/drug effects , Osteoclasts/drug effects , Phytoestrogens/chemistry , Proto-Oncogene Proteins c-fos/drug effects , RANK Ligand/pharmacology , Signal Transduction/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...