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Find video protocols related to scientific articles indexed in Pubmed.
Osteoporosis increases subsequent risk of gallstone: a nationwide population-based cohort study in Taiwan.
BMC Gastroenterol
PUBLISHED: 11-18-2014
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BackgroundOsteopontin (OPN) is a pro-inflammatory cytokine which is expressed in various tissues. It participates in the bone remodeling process and stimulates bone resorption by osteoclasts. It is also a core protein of cholesterol gallstones. We hypothesized osteoporotic patients might have higher risk in developing gallstones and conducted a population-based study to examine the risk of developing gallstone in osteoporotic patients in Taiwan.MethodsA total of 1,638 patients diagnosed with osteoporosis between 2003 and 2005 were identified in the National Health Insurance Research Database. A comparison cohort without osteoporosis (n =6,552) was randomly matched to each osteoporosis patient at a ratio of 4: 1 based on age and sex. A Cox proportional-hazards regression analysis was performed to evaluate the 5-year gallstone-free survival rates for the 2 cohorts.ResultsDuring the 5-year follow-up period, 114 and 311 cases of gallstone occurred in the osteoporosis and comparison cohorts, respectively. After adjusting for the confounders, the Cox regression analysis of the risk of gallstone in the osteoporosis and comparison cohorts yielded a hazard ratio of 1.35 (95% confidence interval: 1.07 - 1.69; p < 0 .01).ConclusionPatients with osteoporosis in Taiwan have a higher risk of developing gallstone than the general population.
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Age-related alterations in the metabolic profile in the hippocampus of the senescence-accelerated mouse prone 8: a spontaneous Alzheimer's disease mouse model.
J. Alzheimers Dis.
PUBLISHED: 10-31-2014
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Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD.
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Decreased EAAT2 protein expression in the essential tremor cerebellar cortex.
Acta Neuropathol Commun
PUBLISHED: 10-15-2014
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Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls.
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Abnormal climbing fibre-Purkinje cell synaptic connections in the essential tremor cerebellum.
Brain
PUBLISHED: 10-01-2014
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Structural changes in Purkinje cells have been identified in the essential tremor cerebellum, although the mechanisms that underlie these changes remain poorly understood. Climbing fibres provide one of the major excitatory inputs to Purkinje cells, and climbing fibre-Purkinje cell connections are essential for normal cerebellar-mediated motor control. The distribution of climbing fibre-Purkinje cell synapses on Purkinje cell dendrites is dynamically regulated and may be altered in disease states. The aim of the present study was to examine the density and distribution of climbing fibre-Purkinje cell synapses using post-mortem cerebellar tissue of essential tremor cases and controls. Using vesicular glutamate transporter type 2 immunohistochemistry, we labelled climbing fibre-Purkinje cell synapses of 12 essential tremor cases and 13 age-matched controls from the New York Brain Bank. Normally, climbing fibres form synapses mainly on the thick, proximal Purkinje cell dendrites in the inner portion of the molecular layer, whereas parallel fibres form synapses on the thin, distal Purkinje cell spiny branchlets. We observed that, compared with controls, essential tremor cases had decreased climbing fibre-Purkinje cell synaptic density, more climbing fibres extending to the outer portion of the molecular layer, and more climbing fibre-Purkinje cell synapses on the thin Purkinje cell spiny branchlets. Interestingly, in essential tremor, the increased distribution of climbing fibre-Purkinje cell synapses on the thin Purkinje cell branchlets was inversely associated with clinical tremor severity, indicating a close relationship between the altered distribution of climbing fibre-Purkinje cell connections and tremor. These findings suggest that abnormal climbing fibre-Purkinje cell connections could be of importance in the pathogenesis of essential tremor.
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Synthesis and SAR studies of novel 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives for anticancer activity.
Br. J. Pharmacol.
PUBLISHED: 09-29-2014
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4-Phenylquinolin-2(1H)-one (4-PQ) derivatives can induce cancer cell apoptosis. Additional new 4-PQ analogs were investigated as more effective, less toxic antitumor agents.
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Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.
Neuron
PUBLISHED: 08-21-2014
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Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2 ± ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2 ± mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2 ± :Atg7(CKO) double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR.
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Sensory axonal dysfunction in cervical radiculopathy.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 08-20-2014
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The aim of this study was to evaluate changes in sensory axonal excitability in the distal nerve in patients with cervical radiculopathy.
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Osteoporosis and the risk of symptomatic nephrolithiasis: a population-based 5-year follow-up study in Taiwan.
Calcif. Tissue Int.
PUBLISHED: 08-15-2014
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This study estimates the risk of symptomatic nephrolithiasis within 5 years of newly diagnosed osteoporosis in a Taiwan population. This cohort study consisted of patients with a diagnosis of osteoporosis between Jan. 2003 and Dec. 2005 (N = 1634). Four age- and gender- matched patients for every patient in the study cohort were selected using random sampling as the comparison cohort (N = 6536). All patients were tracked for 5 years from the date of cohort entry to identify whether they developed symptomatic nephrolithiasis. Cox proportional hazard regressions were performed to evaluate the 5-year nephrolithiasis-free survival rates. During the 5-year follow-up period, 60 osteoporosis patients (3.7%) and 165 non- osteoporosis patients (2.5%) developed symptomatic nephrolithiasis. The adjusted HR of symptomatic nephrolithiasis was 1.38 times greater risk for patients with osteoporosis than for the comparison cohort (95% confidence interval (CI) 1.03-1.86; P < .05). Osteoporosis is very likely to be an independent risk factor for subsequent diagnosis of symptomatic nephrolithiasis.
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MJ-66 induces malignant glioma cells G2/M phase arrest and mitotic catastrophe through regulation of cyclin B1/Cdk1 complex.
Neuropharmacology
PUBLISHED: 08-05-2014
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Malignant gliomas are among the most devastating cancers as they are resistant to many kinds of treatment. Despite recent advances in the diagnosis and treatment, the prognosis of patients remains very poor and the development of new drug is urgently needed. Here, we report that a synthetic quinazolinone analog 2-(naphthalene-1-yl)-6-pyrrolidinyl-4-quinazolinone (MJ-66) induced glioma cell death. Immunofluorescence staining showed that MJ-66-induced cell death was associated with multinucleated phenotype and multipolar spindles that were typical characteristics of mitotic catastrophe. Flow cytometry analysis revealed that MJ-66 caused glioma cell cycle arrest at G2/M phase and increased the proportion of polyploidy cells. Western blotting indicated that the expression of cyclin B1, Cdk1 pY15 and Cdk1 increased after treatment with MJ-66. MJ-66 effectively inhibited tumor growth and induced apoptosis in the xenograft animal model of U87 human glioma cells. Together, these results suggest that MJ-66 inhibited malignant gliomas growth through inducing mitotic catastrophe by interference with G2/M cell cycle checkpoint which may open a new avenue for the treatment of malignant gliomas.
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Design, synthesis, mechanisms of action, and toxicity of novel 20(s)-sulfonylamidine derivatives of camptothecin as potent antitumor agents.
J. Med. Chem.
PUBLISHED: 07-08-2014
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Twelve novel 20-sulfonylamidine derivatives (9a-9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Compound 9a demonstrated better cytotoxicity against MDR cells compared with that of 1 and 3. Mechanistically, 9a induced significant DNA damage by selectively inhibiting Topoisomerase (Topo) I and activating the ATM/Chk related DNA damage-response pathway. In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg. Notably, 9a at 300 mg/kg (i.p.) showed no overt toxicity in contrast to 1 (LD50 56.2 mg/kg, i.p.) and 3 (LD50 177.5 mg/kg, i.p.). Intact 9a inhibited Topo I activity in a cell-free assay in a manner similar to that of 1, confirming that 9a is a new class of Topo I inhibitor. 20-Sulfonylamidine 1-derivative 9a merits development as an anticancer clinical trial candidate.
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The anti-tumor efficiency of pterostilbene is promoted with a combined treatment of Fas signaling or autophagy inhibitors in triple negative breast cancer cells.
Food Funct
PUBLISHED: 06-20-2014
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High expression of vimentin, a canonical mesenchymal marker, is linked with poor prognosis in triple negative breast cancer (TNBC), implying that vimentin may be a potential biomarker in the application of TNBC therapy. Pterostilbene (PTE) has shown anti-invasion activity, and thus, we investigated whether PTE inhibited the epithelial-mesenchymal transition (EMT) in TNBC. Here, we show that PTE decreases the vimentin expression, but that the effect was transient. PTE stimulated Fas signaling, which drives EMT by the ERK1/2 and GSK3?/?-catenin pathways, supporting Fas signaling induction involved in EMT regulation. PTE also triggered autophagy in TNBC. The treatment of TNBC with 3-methyladenine an autophagy inhibitor, not only sustained PTE-inhibited EMT but also significantly promoted anti-proliferation, which indicates that autophagy plays a cyto-protective role and is associated with EMT. Taken together, these data showed that Fas signaling and autophagy accelerated the aggressiveness of TNBC. Inhibition of autophagy or Fas signaling may provide novel targets for TNBC therapy.
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Hypolipidemic activity of Taraxacum mongolicum associated with the activation of AMP-activated protein kinase in human HepG2 cells.
Food Funct
PUBLISHED: 06-07-2014
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This study investigated the hypolipidemic effect and potential mechanisms of T. mongolicum extracts. T. mongolicum was extracted by refluxing three times with water (TM-1), 50% ethanol (TM-2) and 95% ethanol (TM-3). TM-2 contained components with the most effective hypolipidemic potentials in HepG2 cells. Extended administration of TM-2 stimulated a significant reduction in body weight and levels of serum triglyceride LDL-C and total cholesterol in rats. To evaluate the bioactive compounds, we successively fractionated TM-2 with n-hexane (TM-4), dichloromethane (TM-5), ethyl acetate (TM-6), and water (TM-7). TM-4 fraction had the most effective hypolipidemic potential in HepG2 cells, and it decreased the expression of fatty acid synthase (FASN) and inhibited the activity of acetyl-coenzyme A carboxylase (ACC) through the phosphorylation of AMP-activated protein kinase (AMPK). Linoleic acid, phytol and tetracosanol are bioactive compounds identified from TM-4. These results suggest that T. mongolicum is expected to be useful for hypolipidemic effects.
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Cellular density in the cerebellar molecular layer in essential tremor, spinocerebellar ataxia, and controls.
Parkinsonism Relat. Disord.
PUBLISHED: 05-12-2014
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It would be useful to identify additional postmortem markers of Purkinje cell loss in essential tremor (ET). In hereditary cerebellar ataxia, Purkinje cell loss has been reported to result in a secondary increase in the density of the remaining cell populations in the cerebellar molecular layer. However, this phenomenon has not been studied in ET. We quantified cerebellar molecular layer cellular density in 15 ET cases, 15 controls, and 7 spinocerebellar ataxia (SCA) cases (2:2:1 ratio).
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The methanol extract of Euonymus laxiflorus, Rubia lanceolata and Gardenia jasminoides inhibits xanthine oxidase and reduce serum uric acid level in rats.
Food Chem. Toxicol.
PUBLISHED: 04-30-2014
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Chinese herbal medicinal plants, Euonymus laxiflorus (EL), Rubia lanceolata (RL) and Gardenia jasminoides (GJ), have been used wildly to treat arthritis and gout in Taiwan for decades. To understand the beneficial effects of these three plants, their xanthine oxidase (XO) inhibitory activity in vitro and hypouricaemic activity in vivo were investigated. Our results suggested that methanol extracts were better than water extracts for inhibition of XO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, except the water extract of GJ, which exhibited the strongest radical scavenging effect. In animal study, the serum urate level was significantly decreased after oral administration of higher dose (0.39g/kg) methanol extract of the mixture of three plants (ERG). In addition, methanol extract of ERG reduced the pain reaction time in the second phase of formalin induced pain. The results provide useful information on the pharmacological activities of these plants for the potential in treating hyperuricemia.
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Multiple system atrophy and amyotrophic lateral sclerosis in a family with hexanucleotide repeat expansions in C9orf72.
JAMA Neurol
PUBLISHED: 04-16-2014
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Here we report a family with coexistence of multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS) with hexanucleotide repeat expansions in C9orf72.
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Induction of apoptosis in human DU145 prostate cancer cells by KHC-4 treatment.
Chin J Physiol
PUBLISHED: 04-04-2014
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Prostate cancer (CaP) is one of the most prevalent cancers worldwide and the incidence and mortality rates have been rapidly increasing in recent years in Taiwan. Therefore, it is important to development anti-cancer therapy. In this study, KHC-4 was identified from 2-phenyl-4-quionolone derivatives in human prostate cancer cells and as a potential antitumor agent. In this study, we have identified KHC-4 induced apoptosis effects in castration-resistant prostate cancer DU145 cells, and the IC?? value of KHC-4 was 0.1 ?M. KHC-4 suppressed the survival signaling p-PI3K and p-Akt and protein levels of Bcl-2 and Bcl-xL, upregulated Bax, cytochrome c and Caspase 8/9 and induced apoptosis by mitochondrial-dependent pathway. In JC-1 assay monitored the loss of membrane potential in KHC-4 treatments. TUNEL assay results showed DNA fragmentation in KHC-4 induced apoptosis. We concluded that KHC-4 exerted anti-tumor effects in DU145 cells by induction of apoptosis.
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Epinephrine as adjuvant for propranolol produces a marked peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.
Eur. J. Pharmacol.
PUBLISHED: 03-28-2014
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The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95-2.21) ?mol/kg]>propranolol [9.21 (9.08-9.42) ?mol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012 ?mol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012 ?mol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012 ?mol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia.
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Quinazoline analog HMJ-30 inhibits angiogenesis: involvement of endothelial cell apoptosis through ROS-JNK-mediated death receptor 5 signaling.
Oncol. Rep.
PUBLISHED: 03-26-2014
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The aim of the present study was to explore the effect of 6-fluoro-2-(3-fluorophenyl)-4-(cyanoanilino) quinazoline (HMJ-30) on the anti-angiogenic properties and apoptosis-related mechanism of human umbilical vein endothelial cells (HUVECs). In this study, HMJ-30 dose- and time-dependently inhibited the viability of HUVECs. We also found that HMJ-30 enhanced disruption of tube-like structures and suppressed cell migration in HUVECs after vascular endothelial growth factor (VEGF) induction. HMJ-30 was also observed to inhibit vessel branching and sprouting in chicken chorioallantoic membrane (CAM). Microsprouting induced by VEGF in the rat aortic ring and blood vessel formation in a mouse Matrigel plug were individually suppressed by HMJ-30. In an in vitro study, HMJ-30 induced the apoptotic death of HUVECs as indicated by DNA fragmentation and promoted reactive oxygen species (ROS) production as determined by flow cytometric assay. In addition, extrinsic caspase signaling (caspase-8 and -3) was activated in the HMJ-30-treated HUVECs and their inhibitors were applied to assess the signal transduction. We investigated the upstream of the death receptor pathway and further observed that the levels of death receptor 5 (DR5) and phosphorylated c-Jun N-terminal kinase (JNK) signals were upregulated in HUVECs following HMJ-30 challenge, which was confirmed by a JNK-specific inhibitor (SP600125). Hence, HMJ-30-induced endothelial cell apoptosis involved the ROS/JNK-regulated DR5 pathway. In summary, HMJ-30 may provide a potential therapeutic effect for the anti-vascular targeting of angiogenesis during cancer treatment.
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EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone H4.
Dev. Cell
PUBLISHED: 03-21-2014
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Posttranslational modifications of histones play fundamental roles in many biological functions. Specifically, histone H4-K20 methylation is critical for DNA synthesis and repair. However, little is known about how these functions are regulated by the upstream stimuli. Here, we identify a tyrosine phosphorylation site at Y72 of histone H4, which facilitates recruitment of histone methyltransferases (HMTases), SET8 and SUV4-20H, to enhance its K20 methylation, thereby promoting DNA synthesis and repair. Phosphorylation-defective histone H4 mutant is deficient in K20 methylation, leading to reduced DNA synthesis, delayed cell cycle progression, and decreased DNA repair ability. Disrupting the interaction between epidermal growth factor receptor (EGFR) and histone H4 by Y72 peptide significantly reduced tumor growth. Furthermore, EGFR expression clinically correlates with histone H4-Y72 phosphorylation, H4-K20 monomethylation, and the Ki-67 proliferation marker. These findings uncover a mechanism by which EGFR transduces signal to chromatin to regulate DNA synthesis and repair.
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Sialendoscopy With Holmium:YAG Laser Treatment for Multiple Large Sialolithiases of the Wharton Duct: A Case Report and Literature Review.
J. Oral Maxillofac. Surg.
PUBLISHED: 03-17-2014
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Sialolithiasis is defined as calcified stone(s) in the salivary duct or glands. Submandibular gland sialolithiasis is the most common (80 to 90%), followed by parotid gland sialolithiasis (5 to 15%). The typical clinical presentation is salivary gland swelling after eating. As the swelling persists, symptoms owing to local inflammation, such as pain and trismus, emerge. In severe cases, cellulitis and even abscess formation occur and subsequently lead to salivary gland atrophy or fistula formation if the sialolithiasis remains untreated. The most common treatment is complete excision of the affected gland together with the stone(s). In some cases, intraoral sialolithotomy is performed when the stone is solitary and easily palpable through the oral cavity. Sialendoscopy is increasingly performed because of its minimal invasiveness. The major limitation of endoscopic laser lithotripsy of the salivary glands is the size of the stone. Often, for a stone larger than 4 mm, multiple fragmentations of the stone into small pieces is necessary before the pieces can be removed by wire basket or grasping forceps. Recently, the holmium:YAG laser has been reported as quite effective in removing larger salivary gland stones. However, sialoendoscopic laser lithotripsy is a very time-consuming procedure and in most cases, when there are multiple large stones in a single gland, entire gland excision is recommended. This report describes a male patient diagnosed with multiple large stones in his left submandibular gland who was successfully treated under sialendoscopy with holmium:YAG laser lithotripsy.
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CCT327 enhances TRAIL-induced apoptosis through the induction of death receptors and downregulation of cell survival proteins in TRAIL-resistant human leukemia cells.
Oncol. Rep.
PUBLISHED: 03-07-2014
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Tumor necrosis factor-related apoptosis?inducing ligand (TRAIL) has potential application in cancer therapy and it has the ability to selectively kill cancer cells without affecting normal cells. However, the development of resistance to TRAIL in cancer cells cannot be avoided. This study investigated the effects of 2-(5-methylselenophen?2?yl)?6,7?methylenedioxyquinolin?4-one (CCT327), an analogue of quinolin-4-one, on the sensitization of cancer cells to TRAIL and on TRAIL?induced apoptosis in TRAIL?resistance human leukemia cells (HL60?TR). We found that CCT327 enhanced TRAIL?induced apoptosis through upregulation of death receptors DR4 and DR5. In addition to upregulating DRs (death receptors), CCT327 suppressed the expression of decoy receptor DcR1 and DcR2. CCT327 significantly downregulated the expression of FLICE inhibitory protein (cFLIP) and other antiapoptotic proteins. We also demonstrated that CCT327 could activate p38 and JNK. Moreover, CCT327-induced induction of DR5 and DR4 was mediated by reactive oxygen species (ROS), and N-acetylcysteine (NAC) blocked the induction of DRs by CCT327. Taken together, these results showed that CCT327 combined with TRAIL treatment may provide an effective therapeutic strategy for cancer.
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The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg?related proteins in cisplatin?resistant CAR human oral cancer cells.
Int. J. Oncol.
PUBLISHED: 03-06-2014
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Pterostilbene is an effective chemopreventive agent against multiple types of cancer cells. A novel pterostilbene derivative, ANK-199, was designed and synthesized by our group. Its antitumor activity and mechanism in cisplatin-resistant CAR human oral cancer cells were investigated in this study. Our results show that ANK-199 has an extremely low toxicity in normal oral cell lines. The formation of autophagic vacuoles and acidic vesicular organelles (AVOs) was observed in the ANK-199-treated CAR cells by monodansylcadaverine (MDC) and acridine orange (AO) staining, suggesting that ANK-199 is able to induce autophagic cell death in CAR cells. Neither DNA fragmentation nor DNA condensation was observed, which means that ANK-199-induced cell death is not triggered by apoptosis. In accordance with morphological observation, 3-MA, a specific inhibitor of PI3K kinase class III, can inhibit the autophagic vesicle formation induced by ANK-199. In addition, ANK-199 is also able to enhance the protein levels of autophagic proteins, Atg complex, beclin 1, PI3K class III and LC3-II, and mRNA expression of autophagic genes Atg7, Atg12, beclin 1 and LC3-II in the ANK-199-treated CAR cells. A molecular signaling pathway induced by ANK-199 was therefore summarized. Results presented in this study show that ANK-199 may become a novel therapeutic reagent for the treatment of oral cancer in the near future (patent pending).
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Torpedo formation and Purkinje cell loss: modeling their relationship in cerebellar disease.
Cerebellum
PUBLISHED: 03-05-2014
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Torpedo formation and Purkinje cell (PC) loss represent standard and inter-related cerebellar responses to injury. Surprisingly, the nature of their relationship has not been carefully characterized across a range of normal and disease states. Are brains with more torpedoes expected to have fewer PCs? We quantified torpedoes and PCs in four groups: essential tremor (ET), spinocerebellar ataxia (SCA), multiple system atrophy-cerebellar (MSA-C), and controls. Brains from 100 individuals (58 ET, 27 controls, 7 SCA, 8 MSA-C) were available at the New York Brain Bank. After complete neuropathological assessment, a standard parasagittal neocerebellar block was harvested; a 7-?m thick section was stained with Luxol fast blue/hematoxylin and eosin; and torpedoes and PCs were quantified. For a given PC count, SCA and MSA-C cases often had higher torpedo counts than ET cases or controls. Furthermore, the relationship between torpedo and PC counts was complex. The correlation between torpedo and PC counts was negative in ET cases (i.e., individuals with more torpedoes had fewer PCs [i.e., more PC loss]) whereas the relationship was positive in MSA-C cases (i.e., individuals with fewer PCs [i.e., more PC loss] had fewer torpedoes). Patients with SCA showed both patterns. When all diagnostic groups were combined, the correlation was best fit by a quadratic (i.e., parabolic) model rather than a simple linear model; this model incorporated data on the negative correlation in ET cases, the mixed results in SCA cases, and the positive correlation in MSA-C cases (r?=?0.636). The relationship between torpedo and PC counts was complex and heterogeneous across a range of cerebellar disease states, and was best characterized by a quadratic rather than a simple model. With more severe cerebellar disease, torpedoes can be quite numerous and are likely a common feature of surviving PCs, but eventually, dramatic loss of PC leads to a paradoxical reduction in observable torpedoes.
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Cry1 and Tef gene polymorphisms are associated with major depressive disorder in the Chinese population.
J Affect Disord
PUBLISHED: 03-04-2014
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Accumulating evidences indicate that circadian abnormalities lead to sleep disorder, neurodegenerative diseases and depression. We have reported that the polymorphisms of a clock-related gene, Tef, contributed to the risk of sleep disturbances and depression in the Parkinson disease. The objective of the present study was to examine whether the three clock genes we previously studied are associated with major depressive disorder (MDD) in the Chinese population.
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Finite element analysis of helical flows in human aortic arch: a novel index.
Biomicrofluidics
PUBLISHED: 03-01-2014
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This study investigates the helical secondary flows in the aortic arch using finite element analysis. The relationship between helical flow and the configuration of the aorta in patients of whose three-dimensional images constructed from computed tomography scans was examined. A finite element model of the pressurized root, arch, and supra-aortic vessels was developed to simulate the pattern of helical secondary flows. Calculations indicate that most of the helical secondary flow was formed in the ascending aorta. Angle ? between the zero reference point and the aortic ostium (correlation coefficient (r)?=?-0.851, P?=?0.001), the dispersion index of the cross section of the ascending (r?=?0.683, P?=?0.021) and descending aorta (r?=?0.732, P?=?0.010), all correlated closely with the presence of helical flow (P?
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Effect of uvulopalatopharyngoplasty on leptin and endothelial function in sleep apnea.
Ann. Otol. Rhinol. Laryngol.
PUBLISHED: 02-28-2014
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This study evaluated the effects of uvulopalatopharyngoplasty (UPPP) on serum leptin levels and endothelial function in patients with obstructive sleep apnea syndrome (OSAS).
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YC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK.
Br. J. Pharmacol.
PUBLISHED: 02-10-2014
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YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells.
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Low dose of valproate improves motor function after traumatic brain injury.
Biomed Res Int
PUBLISHED: 02-06-2014
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Traumatic brain injuries (TBIs) are a major health care problem worldwide. Approximately 1.5 million new TBI cases occur annually in the United States, with mortality rates ranging between 35% and 40% in severe patients. Despite the incidence of these injuries and their substantial socioeconomic implications, no specific pharmacological intervention is available for clinical use. Several studies have indicated that 300 mg/kg or 400 mg/kg of valproate (VPA) exhibits neuroprotective effects in animal models. However, humans cannot tolerate high doses of VPA. This study aims to investigate whether 30 mg/kg of VPA administered to rats affects TBIs.
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Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria.
Bioorg. Med. Chem.
PUBLISHED: 01-17-2014
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Eight new cardiac glycosides/aglycones (antiaritoxiosides A-G, 1-7, and antiarotoxinin B, 8), two new coumarins (anticarins A-B, 41-42), and two new flavanones (antiarones L-K, 43-44) were isolated from trunk bark of Antiaris toxicaria together with 53 known compounds. The new structures were established by extensive analysis of spectroscopic data. Compound 1 (10-carboxy and 3?-hydroxy) and compounds 3-6 (10-hydroxy) contain unique substituents that are rarely found in cardiac glycosides. The cytotoxic effects of isolated compounds against ten human cancer cell lines, KB, KB-VIN, A549, MCF-7, U-87-MG, PC-3, 1A9, CAKI-1, HCT-9 and S-KMEL-2, were tested using the sulforhodamine B assay. Five compounds (12, 16, 20, 22, and 31) showed significant cytotoxicity against all ten cancer cell lines, with notable potency at the ng/mL level against some cell lines, which merits further development as clinical trial candidates.
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Diameter change of common femoral arteries after percutaneous endovascular aortic repair with the use of the preclose technique.
J. Vasc. Surg.
PUBLISHED: 01-13-2014
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One of the major concerns regarding the preclose technique is its influence on the diameter of the accessed common femoral artery (CFA). The aim of our study was to evaluate the CFA diameter change after percutaneous endovascular aortic repair (PEVAR) with the use of the preclose technique.
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Three new clerodane diterpenes from Polyalthia longifolia var. pendula.
Molecules
PUBLISHED: 01-10-2014
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Three new clerodane diterpenes, (4?2)-abeo-cleroda-2,13E-dien-2,14-dioic acid (1), (4?2)-abeo-2,13-diformyl-cleroda-2,13E-dien-14-oic acid (2), and 16(R&S)- methoxycleroda-4(18),13-dien-15,16-olide (3), were isolated from the unripe fruit of Polyalthia longifolia var. pendula (Annonaceae) together with five known compounds (4-8). The structures of all isolates were determined by spectroscopic analysis. The anti-inflammatory activity of the isolates was evaluated by testing their inhibitory effect on NO production in LPS-stimulated RAW 264.7 macrophages. Among the isolated compounds, 16-hydroxycleroda-3,13-dien-15,16-olide (6) and 16-oxocleroda-3,13-dien-15-oic acid (7) showed promising NO inhibitory activity at 10 µg/mL, with 81.1% and 86.3%, inhibition, respectively.
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Impact of ester promoieties on transdermal delivery of ketorolac.
J Pharm Sci
PUBLISHED: 01-10-2014
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Different types of ketorolac ester prodrugs incorporating tert-butyl (KT), benzyl (KB), heptyl (KH), and diketorolac heptyl (DKH) promoieties were synthesized for the comparison of percutaneous penetration. The prodrugs were characterized according to their melting point, capacity factor, lipophilicity, solubility in 30% ethanol/buffer, enzymatic hydrolysis, in vitro skin permeation, hair follicle accumulation, and in vivo skin tolerance. Interactions between the prodrugs and esterases were predicted by molecular docking. Both equimolar suspensions and saturated solutions in 30% ethanol/pH 7.4 buffer were employed as the applied dose. All of the prodrugs exhibited a lower melting point than ketorolac. The lipophilicity increased in the following order: ketorolac < KT < KB < KH < DKH. The prodrugs were rapidly hydrolyzed to the parent drug in esterase medium, skin homogenate, and plasma, with KT and KB exhibiting higher degradation rates. KT exhibited the highest skin permeation, followed by KB. The flux of KT and KB exceeded that of ketorolac by 2.5-fold and twofold, respectively. KH and DKH did not improve ketorolac permeation but exhibited a sustained release behavior. KT and KH revealed selective absorption into follicles and a threefold greater follicular uptake compared with ketorolac. KB, KH, and DKH slightly but significantly increased transepidermal water loss (TEWL) after consecutive administration for 7 days, whereas ketorolac and KT exhibited no influence on TEWL. According to the experimental results, it can be concluded that an optimal balance between lipophilicity and aqueous solubility is important in the design of a successful prodrug. The acceptable skin tolerance for safe application is also an important consideration.
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Assessment of hearing loss by pure-tone audiometry in patients with mucopolysaccharidoses.
Mol. Genet. Metab.
PUBLISHED: 01-08-2014
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Patients with mucopolysaccharidoses (MPS) often have hearing loss. However, the characterization of hearing loss by pure-tone audiometry (PTA) in this rare disease population and its relationship to age and treatment is limited.
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Aggravated DNA damage as a basis for enhanced glioma cell killing by MJ-66 in combination with minocycline.
Am J Cancer Res
PUBLISHED: 01-01-2014
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Despite recent advances in the treatment of malignant glomas, the prognosis of patients remains very poor and more efficient therapeutic approaches are urgently needed. In the present study, we investigated whether 2-(naphthalene-1-yl)-6-pyrrolidinyl-4-quinazolinone (MJ-66), a synthetic quinazolinone analog, induces glioma cell death through DNA damage. Treatment of C6 glioma cells with MJ-66 resulted in a time-dependent increase in ?-H2AX and increased the appearance of nuclear ?-H2AX foci. MJ-66 interfered with G2/M DNA damage checkpoint through increasing phosphorylated levels of Chk1 and Cdc25C. UCN-01, a Chk1 inhibitor, reversed MJ-66-induced activation of Cdc25C and caspase 3. MJ-66 inhibited tumor growth and prolonged survival time in intracranial glioma xenograft model. The combination of MJ-66 and Mino enhanced DNA damage and synergistically inhibited tumor growth and prolonged survival time in intracranial glioma xenograft model. These results suggest that the combination of MJ-66 and Mino may be developed as a new therapeutic strategy against malignant gliomas.
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Curcumin Suppresses Doxorubicin-Induced Epithelial-Mesenchymal Transition via the Inhibition of TGF-? and PI3K/AKT Signaling Pathways in Triple-Negative Breast Cancer Cells.
J. Agric. Food Chem.
PUBLISHED: 11-21-2013
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Triple-negative breast cancer (TNBC) is defined by a lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER 2). Therefore, targeted therapy agents may not be used, and therapy is largely limited to chemotherapy. Doxorubicin treatment consequently acquires undesired malignance characteristics [i.e., epithelial-mesenchymal transition (EMT) and multi-drug resistance]. Our results illustrated that doxorubicin triggered EMT and resulted in the acquisition of a mesenchymal phenotype in TNBC cells. Moreover, we found that transforming growth factor-? (TGF-?) and PI3K/AKT signaling pathways were acquired for doxorubicin-induced EMT. Interestingly, we found that curcumin suppressed doxorubicin-induced EMT. Curcumin reversed doxorubicin-induced morphological changes, inhibited doxorubicin-induced downregulation of E-cadherin expressions, and inhibited doxorubicin-induced upregulation of vimentin expression. We also found that curcumin inhibited doxorubicin-induced EMT by inhibiting the TGF-? and PI3K/AKT signaling pathways. Moreover, curcumin enhanced the antiproliferative effects of doxorubicin in TNBC cells. In summary, our results suggest that doxorubicin in combination with curcumin may be a potential therapy for TNBC.
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Chemical Constituents and Anticancer Activity of Yellow Camellias against MDA-MB-231 Human Breast Cancer Cells.
J. Agric. Food Chem.
PUBLISHED: 09-24-2013
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Yellow camellia, with its golden yellow flowers, is rare in the world. Most studies of yellow camellia have focused on its ornamental properties; however, there are fewer published studies on its medical values. The purpose of this study was to define the chemical constituents and the biological potential of the water extract of leaves in six species of yellow camellia. The data showed that Camellia murauchii had significantly higher total catechins and total polyphenol content than others; Camellia euphlebia had the highest total amino acids and ?-aminobutyric acid. The results indicated that Camellia tunghinensis exhibited the highest free radical scavenging capacity and showed potent anticancer activities. Camellia nitidissima had stronger inhibitory effect than other species on fatty acid synthesis. In addition to catechins, 3-p-coumaroylquinic acid, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside were detected in C. tunghinensis using liquid chromatography-tandem mass spectrometry. Taken together, yellow camellias possess biological activity and are worthy of continued study.
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Population-based 5-year Follow-up Study in Taiwan of Osteoporosis and Risk of Periodontitis.
J. Periodontol.
PUBLISHED: 09-03-2013
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Objective: Osteoporosis and periodontitis are both considered as the global health issues which threaten postmenopausal women and elder population. However, the correlation between osteoporosis and periodontitis is still unclear. Materials and methods: Using a nationwide Taiwanese population-based database, data from osteoporosis patients (year 2003 to 2005; N = 2527) and 7575 individuals who were matched to each patient by their age and gender were analyzed. All participates were tracked for 5 years from the date of enrollment to observe the percentage of patients who developed periodontitis. Cox proportional hazard regressions were performed to evaluate 5-year periodontitis-free survival rates. Results: Among the total sample, 3060 individuals were diagnosed with periodontitis during the 5-year follow-up period: 792 in the study cohort and 2268 in the comparison cohort. The adjusting hazard ratio (HR) for periodontitis in patients with osteoporosis compared to the non-osteoporosis subjects during the 5-year follow-up was 1.14 (95% confidence interval [CI] = 1.05-1.24, p < 0.01). Conclusions: This population-based study indicated that osteoporosis patients may have an increased risk of periodontitis.
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Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study.
Orphanet J Rare Dis
PUBLISHED: 08-28-2013
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All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed.
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Amyotrophic Lateral Sclerosis and Spinocerebellar Ataxia Type 2 in a Family With Full CAG Repeat Expansions of ATXN2.
JAMA Neurol
PUBLISHED: 08-21-2013
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IMPORTANCE A family with coexistence of spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis (ALS) is described. OBSERVATIONS Intermediate or full CAG repeat expansions of ATXN2 are associated with ALS. However, no coexistence of spinocerebellar ataxia type 2 and ALS in a family has been reported in the literature. We describe a 47-year-old woman with an 11-year history of ataxia and her paternal uncle with ALS who were evaluated at Columbia University Medical Center since July 2006. Both our patient with ataxia and her uncle with ALS have full pathological CAG repeat expansions of ATXN2. CONCLUSIONS AND RELEVANCE The diverse clinical phenotypes of ATXN2 CAG expansions and their coexistence in a single family are highlighted. A clinician should consider the diagnosis of spinocerebellar ataxia type 2 when encountering a patient with ataxia and a family history of ALS.
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A novel emulsion-type adjuvant containing CpG oligodeoxynucleotides enhances CD8(+) T-cell-mediated anti-tumor immunity.
J Control Release
PUBLISHED: 08-15-2013
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PELC is a novel emulsion-type adjuvant that contains the bioresorbable polymer poly (ethylene glycol)-block-poly (lactide-co-?-caprolactone) (PEG-b-PLACL), Span®85 and squalene. To investigate whether PELC is able to enhance CTL responses of antigens for treating tumor, peptides or protein antigens derived from HPV16 E7 were formulated with PELC nanoparticles and CpG oligodeoxynucleotide. We identified that PELC formulation could delay the release of antigens in vitro and in vivo. We assessed the immunogenicity of an H-2D(b)-restricted CTL epitope RAHYNIVTF (RAH) formulated with PELC or PELC/CpG and investigated the ability of these formulations to promote tumor regression. Following a single-dose subcutaneous injection in mice, we found that the RAH peptide formulated with PELC/CpG (RAH/PELC/CpG) resulted in increased numbers of IFN-?-secreting cells and RAH-specific CD8(+) T cells and an enhanced cytotoxic T cell response compared with RAH formulated with PELC or CpG alone. The tumor-bearing mice received a single-dose injection of RAH/PELC/CpG, which induced complete tumor regression. These results demonstrated that peptide antigen formulated with PELC/CpG nanoparticles is feasible for cancer immunotherapy.
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HotLig: a molecular surface-directed approach to scoring protein-ligand interactions.
J Chem Inf Model
PUBLISHED: 08-01-2013
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Accurate prediction of ligand-binding poses is crucial for understanding molecular interactions and is very important for drug discovery, structural design, and optimization. In this study, we developed a novel scoring program, HotLig, which applies the Connolly surface of a protein to calculate hydrophobic interaction and paired pharmacophore interactions with ligands. In addition to molecular surface distance, ligand-contacting areas and hydrogen-bond angles were also introduced to the scoring functions in HotLig. Four individual energy scoring functions for H-bonds, ionic pairs, metal coordination, and hydrophobic effects were derived from 600 protein-ligand complexes, and then, their weighting factors were optimized through an interaction-characterized training set. Success rates of ligand-binding-pose predictions (with a root mean squared deviation of ?2 Å) for the Wang, GOLD, and Cheng data sets were respectively validated to be 91.0%, 87.0%, and 85.6%. HotLig was found to possess equally good predictive powers for the hydrophilic (88.6%) and hydrophobic subsets (87.5%), and the success rate for the mixed subset was as high as 96.9%. The Spearman correlation coefficients were as good as 0.609 to 0.668, which indicates HotLig also has satisfactory predictive power for binding affinities. These results suggested that the HotLig can analyze diverse ligands, including peptides, and is expected to be a powerful tool for drug design and discovery.
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The novel synthetic compound 6-acetyl-9-(3,4,5-trimetho-xybenzyl)-9H-pyrido[2,3-b]indole induces mitotic arrest and apoptosis in human COLO 205 cells.
Int. J. Oncol.
PUBLISHED: 07-05-2013
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A novel synthetic compound 6-acetyl-9-(3,4,5-trimetho-xybenzyl)-9H-pyrido[2,3-b]indole (HAC-Y6) demonstrated selective anticancer activity. In the present study, COLO 205 cells were treated with HAC-Y6 to investigate the molecular mechanisms underlying its effects. HAC-Y6 induced growth inhibition, G2/M arrest and apoptosis in COLO 205 cells with an IC50 of 0.52±0.035 µM. Annexin V/PI double staining demonstrated the presence of apoptotic cells. JC-1 staining analysis showed that HAC-Y6 decreased mitochondrial membrane potential in support of apoptosis. An immunostaining assay revealed that HAC-Y6 depolymerized microtubules. Treatment of COLO 205 cells with HAC-Y6 resulted in increased expression of BubR1 and cyclin B1 and decreased expression of aurora A, phospho-aurora A, aurora B, phospho-aurora B and phospho-H3. HAC-Y6 treatment increased protein levels of active caspase-3, caspase-9, Endo G, AIF, Apaf-1, cytochrome c and Bax, but treatment with the compound caused reduced levels of procaspase-3, procaspase-9, Bcl-xL and Bcl-2. Overall, our results suggest that HAC-Y6 exerts anticancer effects by disrupting microtubule assembly and inducing G2/M arrest, polyploidy and apoptosis via mitochondrial pathways in COLO 205 cells.
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Neonatal orbital abscess.
Pediatr Int
PUBLISHED: 06-21-2013
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Orbital abscess is life-threatening and rare in children. Reported herein is a term male neonate who had methicillin-resistant Staphylococcus aureus orbital abscess, and a literature review of this disease. A total of 16 neonates diagnosed with neonatal orbital abscess are reported in the literature. There is a mild male predilection and two neonates were delivered prematurely. Leukocytosis, fever, ethmoiditis and associated upper respiratory tract infection were found in approximately half of them. Eight neonates had sepsis and 14 patients underwent surgical intervention. One patient died. Staphylococcus aureus was identified in 14 out of 17 patients. Neonatal orbital abscess is rarely encountered but may be fatal. Although streptococci are prevalent in childhood orbital infection, S. aureus was predominant in neonatal orbital abscess in the present series. Appropriate antimicrobial therapy against S. aureus is essential in treating neonatal orbital abs ess. This case suggests that a higher initial dose of vancomycin may be an effective and safe strategy for severe S. aureus infection in neonates.
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Mechanistic studies on regioselective dephosphorylation of phosphate prodrugs during a facile synthesis of antitumor phosphorylated 2-phenyl-6,7-methylenedioxy-1H-quinolin-4-one.
Molecules
PUBLISHED: 05-13-2013
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Phosphorylation of 2-(3-hydroxy-5-methoxyphenyl)-6,7-methylenedioxy-1H-quinolin-4-one (1) afforded diphosphate 2. We found that, upon treatment with methanol under mild conditions, 2 can undergo facile and highly regioselective dephosphorylation to give the monophosphate 3, with a phosphate group remaining on the phenyl ring. The details of the dephosphorylation process were postulated and then probed by LC-MS and HPLC analyses. Furthermore, as a preliminary study, the water soluble monophosphate prodrug 4 was tested for antitumor activity against a MCF-7 xenograft nude mice model.
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Design and synthesis of 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives as novel anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase.
Bioorg. Med. Chem.
PUBLISHED: 05-09-2013
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Novel 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives 12a-n were designed and prepared through an intramolecular cyclization reaction and evaluated for in vitro anticancer activity. Among the synthesized compounds, 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) displayed potent cytotoxicity against several different tumor cell lines at a sub-micromolar level. Furthermore, results of fluorescence-activated cell sorting (FACS) analysis suggested that 12e induced cell cycle arrest in the G2/M phase accompanied by apoptosis in HL-60 and H460 cells. This action was confirmed by Hoechst staining and caspase-3 activation. Due to their easy synthesis and remarkable biological activities, 4-phenylquinolin-2(1H)-one analogs (4-PQs) are promising new anticancer leads based on the quinoline scaffold. Accordingly, compound 12e was identified as a new lead compound that merits further optimization and development as an anticancer candidate.
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A dose-response study on the efficacy of tricyclic antidepressants on reducing morphine-withdrawal symptoms.
Acta Anaesthesiol Taiwan
PUBLISHED: 05-04-2013
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Acute detoxification may lead to withdrawal syndrome. The syndrome is sufficiently aversive in those who are morphine-dependents and thus it hinders abstinence. The opioids are most often used clinically to lighten this syndrome. Here, we evaluated the effects of tricyclic antidepressants (TCAs) in treating physical dependence to opioids upon acute detoxification in mice.
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Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead.
Bioorg. Med. Chem. Lett.
PUBLISHED: 05-03-2013
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New 6- (or 6,7-) substituted 2-(hydroxyl substituted phenyl)quinolin-4-one derivatives were synthesized and screened for antiproliferative effects against cancer cell lines. Structure-activity relationship correlations were established and the most promising compound 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidin-1-ylquinolin-4-one (6h) exhibited strong inhibitory activity against various human cancer cell lines, particularly non-small cell lung cancer NCI-H522. Additional studies suggested a mechanism of action resembling that of the antimitotic drug vincristine. The presence of a C-ring OH group in 6h will allow this compound to be converted readily to a water soluble and physicochemically stable hydrophilic prodrug. Compound 6h is proposed as a new anticancer lead compound.
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Bacterial etiology of acute otitis media in the era prior to universal pneumococcal vaccination in Taiwanese children.
J Microbiol Immunol Infect
PUBLISHED: 04-25-2013
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Acute otitis media (AOM) is one of the most frequent bacterial infections in children. Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) are the two major bacterial pathogens. Pneumococcal conjugate vaccine was introduced into Taiwan in 2005 and only some children were vaccinated. This retrospective study assessed the bacterial etiology of AOM and its antimicrobial susceptibility in the era prior to universal pneumococcal vaccination in Taiwan.
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Systemic diphenidol reduces neuropathic allodynia and TNF-alpha overexpression in rats after chronic constriction injury.
Neurosci. Lett.
PUBLISHED: 04-05-2013
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Diphenidol has been shown to block voltage-gated Na(+) channels, which are associated with specific types of pain. Here, we evaluated the effects of diphenidol on chronic constriction injury (CCI)-evoked allodynia and expression of tumor necrosis factor-? (TNF-?). A peripheral nerve injury was elicited in rats by placing four loosely constrictive ligatures around the sciatic nerve. After intraperitoneal injection of diphenidol, rats were tested for evidence of mechanical allodynia prior to surgery, and on postoperative days 3, 6, 7, 11, 13 and 14. We showed that CCI rats received diphenidol caused dose-dependent increases in mechanical withdrawal threshold. Both diphenidol 2 and 10 ?mol/kg groups, but not 0.4 ?mol/kg diphenidol, displayed lower TNF-? level in the sciatic nerve than the CCI group (P<0.05) on day 7 after CCI. Our results support the conclusion that systemic diphenidol produced a dose-related inhibition of mechanical allodynia following chronic constriction injury of the sciatic nerve. This antiallodynic effect is related to the decrease of TNF-? expression in the sciatic nerve of CCI rats.
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The role of the Ala746Thr variant in the ATP13A2 gene among Chinese patients with Parkinsons disease.
J Clin Neurosci
PUBLISHED: 03-20-2013
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The association between idiopathic Parkinsons disease (PD) and the ATP13A2 (PARK9) Ala746Thr variant, associated with Kufor-Rakeb syndrome, is controversial. We investigated this association in 69 patients with early onset PD (EOPD; ?50 years of age), 192 patients with late onset PD (LOPD; >50 years of age), and 180 healthy controls in the Chinese population in Hong Kong. The presence of the Ala746Thr variant in the ATP13A2 locus was examined in all participants. We detected the heterozygous Ala746Thr variant in one healthy control (0.6%), one patient with EOPD (1.4%, p=0.50), and one patient with LOPD (0.5%, p=0.96). We suggest that the ATP13A2 Ala746Thr variant is not a common risk factor for PD in the Chinese population in Hong Kong.
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Lingo-1 expression is increased in essential tremor cerebellum and is present in the basket cell pinceau.
Acta Neuropathol.
PUBLISHED: 03-17-2013
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The Lingo-1 sequence variant has been associated with essential tremor (ET) in several genome-wide association studies. However, the role that Lingo-1 might play in pathogenesis of ET is not understood. Since Lingo-1 protein is a negative regulator of axonal regeneration and neurite outgrowth, it could contribute to Purkinje cell (PC) or basket cell axonal pathology observed in postmortem studies of ET brains. In this study, we used Western blotting and immunohistochemistry to examine Lingo-1 protein in ET vs. control brains. In Western blots, Lingo-1 protein expression level was significantly increased in cerebellar cortex (1.56 ± 0.46 in ET cases vs. 0.99 ± 0.20 in controls, p = 0.002), but was similar in the occipital cortex (p = 1.00) of ET cases vs. controls. Lingo-1 immunohistochemistry in cerebellum revealed that Lingo-1 was enriched in the distal axonal processes of basket cells, which formed a "pinceau" structure around the PC axon initial segment (AIS). We found that some Lingo-1-positive pinceau had abnormally elongated processes, targeting PC axon segments distal to the AIS. In ET cases, the percentage of Lingo-1-positive pinceau that were ?30 or ?40 ?m in length was increased 2.4- to 4.1-fold, respectively, vs. pinceau seen in control brains (p < 0.0001). Elongated Lingo-1-positive pinceau strongly correlated with number of PC axonal torpedoes and a rating of basket cell axonal pathology. The increased cerebellar Lingo-1 expression and elongated Lingo-1-positive pinceau processes could contribute to the abnormal PC and basket cell axonal pathology and cerebellar dysfunction observed in ET.
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The novel carboxamide analog ITR-284 induces caspase-dependent apoptotic cell death in human hepatocellular and colorectal cancer cells.
Mol Med Rep
PUBLISHED: 03-05-2013
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We have previously reported that ITR-284, a potent carboxamide-derived anticancer agent, induced apoptosis in leukemia cells. However, there are no reports showing that ITR-284 inhibits human hepatocellular and colorectal cancer cells. In this study, we investigated the antiproliferative effects and apoptotic induction of ITR-284 on various types of human hepatocellular and colorectal cancer cells in vitro. The growth inhibition effect of ITR-284 on cancer cells was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Cell morphology was examined under a phase-contrast microscope. The activities of caspase-3, -8 and -9 were determined by caspase colorimetric assay. ITR-284 reduced the cell viability in human hepatocellular cancer cells (Hep G2, Hep 3B, SK-HEP-1 and J5) and colorectal cancer cells (HT 29, COLO 205, HCT 116 and SW 620). ITR-284 had highly selective effects on Hep 3B and COLO 205 cells. ITR-284 stimulated morphological changes of Hep 3B and COLO 205 cells. The activation of caspase-3, -8 and -9 contributed to ITR-284-induced apoptosis. ITR-284-triggered growth inhibition was significantly attenuated by the inhibitors of caspase-3, -8 and -9 in Hep 3B and COLO 205 cells. ITR-284 induced apoptosis in Hep 3B and COLO 205 cells through the caspase cascade-dependent signaling pathway.
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CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo.
Oncol. Rep.
PUBLISHED: 02-21-2013
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HER2 has become a solicitous therapeutic target in metastatic and clinical drug-resistant cancer. Here, we evaluated whether or not 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) and its furopyrazole and thienopyrazole analogues repress the expression of the HER2 protein. Among the test compounds, (1-benzyl-3-(p-hydroxymethylphenyl)-5-methylfuro[3,2-c]pyrazol) (CLC604), an isosteric analogue of YC-1, significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing cancer cells. Our results revealed that CLC604 reduced HER2 expression through a post-transcriptional mechanism and involvement of proteasomal activity. CLC604 disrupted the association of 90-kDa heat shock protein (Hsp90) with HER2 resulting from the inhibition of Hsp90 ATPase activity. Moreover, we found that CLC604 significantly enhanced the antitumor efficacy of clinical drugs against HER2-overexpressing tumors and efficiently reduced HER2-induced drug resistance in vitro and in vivo. These findings suggest that CLC604 should be developed further as a novel antitumor drug candidate for the treatment of drug-resistant cancer.
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Synthesis and anticancer activity of 2,4-disubstituted furo[3,2-b]indole derivatives.
Eur J Med Chem
PUBLISHED: 02-08-2013
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We synthesized and evaluated a series of 2,4-disubstituted furo[3,2-b]indole derivatives for anticancer activity and established the structure-activity relationships (SARs) of these compounds. Among all tested compounds, we found (5-((2-(hydroxymethyl)-4H-furo[3,2-b]indol-4-yl)methyl)furan-2-yl)methanol (10a) to be the most promising agent. In screening against NCI-60 human tumor cell lines, 10a exhibited highly selective anticancer activity and significant inhibitory activity against A498 renal cancer cells. Our COMPARE analysis results suggest that the 10a fingerprint is similar to that of NSC-754549, which is an isostere of YC-1. We further confirmed the significant antitumor activity of compound 10a with tests in the A498 xenograft nude mice model. Therefore, compound 10a should be further developed as a new drug candidate for treating renal cancer.
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Characterization of pulmonary function impairments in patients with mucopolysaccharidoses-changes with age and treatment.
Pediatr. Pulmonol.
PUBLISHED: 02-08-2013
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BACKGROUND: The mucopolysaccharidoses (MPS) comprise a group of inherited lysosomal storage disorders characterized by deficiencies in enzymes catalyzing the degradation of glycosaminoglycans. Impairment of pulmonary function is an important health problem for patients with MPS. However, there are few published reports on the prevalence and severity of pulmonary dysfunction in relation to age and treatment in this disorder. METHODS: To evaluate pulmonary function in patients with MPS, we performed spirometry in 35 patients (22 males and 13 females; 1 with MPS I, 12 with MPS II, 16 with MPS IVA, and 6 with MPS VI; mean age, 14.6?±?5.9 years; age range, 6.4 years to 33 years). Forced vital capacity (FVC), forced expired volume in 1?sec (FEV(1) ), FEV(1) to FVC ratio (FEV1/FVC), peak expiratory flow (PEF), and mean forced expiratory flow during the middle half of FVC (FEF(25-75%) ) were measured. RESULTS: Mean FVC, FEV(1) , PEF, and FEF(25-75%) were 74.2%, 73.9%, 64.7%, and 37.1% of the predicted values, respectively. By spirometric classification, 32 patients (91%) had small airway disease (FEF(25-75%) ?
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Cyclohexylmethyl Flavonoids Suppress Propagation of Breast Cancer Stem Cells via Downregulation of NANOG.
Evid Based Complement Alternat Med
PUBLISHED: 02-07-2013
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Breast cancer stem cells (CSCs) are highly tumorigenic and possess the capacity to self-renew. Recent studies indicated that pluripotent gene NANOG involves in regulating self-renewal of breast CSCs, and expression of NANOG is correlated with aggressiveness of poorly differentiated breast cancer. We initially confirmed that breast cancer MCF-7 cells expressed NANOG, and overexpression of NANOG enhanced the tumorigenicity of MCF-7 cells and promoted the self-renewal expansion of CD24(-/low)CD44(+) CSC subpopulation. In contrast, knockdown of NANOG significantly affected the growth of breast CSCs. Utilizing flow cytometry, we identified five cyclohexylmethyl flavonoids that can inhibit propagation of NANOG-positive cells in both breast cancer MCF-7 and MDA-MB231 cells. Among these flavonoids, ugonins J and K were found to be able to induce apoptosis in non-CSC populations and to reduce self-renewal growth of CD24(-/low)CD44(+) CSC population. Treatment with ugonin J significantly reduced the tumorigenicity of MCF-7 cells and efficiently suppressed formation of mammospheres. This suppression was possibly due to p53 activation and NANOG reduction as either addition of p53 inhibitor or overexpression of NANOG can counteract the suppressive effect of ugonin J. We therefore conclude that cyclohexylmethyl flavonoids can possibly be utilized to suppress the propagation of breast CSCs via reduction of NANOG.
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Interplay of LRRK2 with chaperone-mediated autophagy.
Nat. Neurosci.
PUBLISHED: 01-31-2013
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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinsons disease. We found LRRK2 to be degraded in lysosomes by chaperone-mediated autophagy (CMA), whereas the most common pathogenic mutant form of LRRK2, G2019S, was poorly degraded by this pathway. In contrast to the behavior of typical CMA substrates, lysosomal binding of both wild-type and several pathogenic mutant LRRK2 proteins was enhanced in the presence of other CMA substrates, which interfered with the organization of the CMA translocation complex, resulting in defective CMA. Cells responded to such LRRK2-mediated CMA compromise by increasing levels of the CMA lysosomal receptor, as seen in neuronal cultures and brains of LRRK2 transgenic mice, induced pluripotent stem cell-derived dopaminergic neurons and brains of Parkinsons disease patients with LRRK2 mutations. This newly described LRRK2 self-perpetuating inhibitory effect on CMA could underlie toxicity in Parkinsons disease by compromising the degradation of ?-synuclein, another Parkinsons disease-related protein degraded by this pathway.
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Biodegradable cisplatin-eluting tracheal stent for malignant airway obstruction: in vivo and in vitro studies.
Chest
PUBLISHED: 01-26-2013
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Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems.
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AKT serine/threonine protein kinase modulates baicalin-triggered autophagy in human bladder cancer T24 cells.
Int. J. Oncol.
PUBLISHED: 01-23-2013
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Baicalin is one of the major compounds in the traditional Chinese medicinal herb from Scutellaria baicalensis Georgi. We investigated the molecular mechanisms of cell autophagy induced by baicalin in human bladder cancer T24 cells. Baicalin inhibited cell survival as shown by MTT assay and increased cell death by trypan blue exclusion assay in a concentration-dependent manner. Baicalin did not induce apoptotic cell death in T24 cells by TUNEL and caspase-3 activity assay. Baicalin induced the acidic vesicular organelle cell autophagy marker, manifested by acridine orange (AO) and monodansylcadaverine (MDC) staining and cleavage of microtubule-associated protein 1 light chain 3 (LC3). The protein expression levels of the Atg 5, Atg 7, Atg 12, Beclin-1 and LC3-II were upregulated in T24 cells after baicalin treatment. Inhibition of autophagy by 3-methyl-adenine (an inhibitor of class III phosphatidylinositol-3 kinase; 3-MA) reduced the cleavage of LC3 in T24 cells after baicalin treatment. Furthermore, protein expression levels of phospho-AKT (Ser473) and enzyme activity of AKT were downregulated in T24 cells after baicalin treatment. In conclusion, baicalin triggered cell autophagy through the AKT signaling pathway in T24 cells.
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Inhibition of formyl peptide-stimulated superoxide anion generation by Fal-002-2 occurs mainly through the blockade of the p21-activated kinase and protein kinase C signaling pathways in ratneutrophils.
Eur. J. Pharmacol.
PUBLISHED: 01-16-2013
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In formyl-Met-Leu-Phe (fMLP)-stimulated rat neutrophils, a synthetic compound, 6-chloro-2-(2-chlorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Fal-002-2), inhibited superoxide anion (O2(•-)) generation with an IC50 value of about 11?M, which was not mediated by scavenging the generated O2(•-) or by a cytotoxic effect on neutrophils. Fal-002-2 effectively attenuated the phosphorylation of Ser residues in p47(phox) and the association between p47(phox) and p22(phox) in fMLP-stimulated neutrophils. The interaction of p47(phox) with protein kinase C (PKC) isoforms (?, ?I, ?II, ? and ?) was attenuated by Fal-002-2 with a similar IC50 value to that required for inhibition of O2(•-) generation, whereas Fal-002-2 had no prominent effect on PKC isoform membrane translocation and did not affect the kinase activity. Moreover, Fal-002-2 had no effect on the phosphorylation of Akt and downstream glycogen synthase kinase-3?, only slightly affected the intracellular free Ca(2+) concentration, phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase (MAPK), but effectively attenuated the downstream MAPK-activated protein kinase-2 phosphorylation. The interaction of p21-activated kinase (PAK) 1with p47(phox), phosphorylation of PAK1 (Thr423/Ser144) and the membrane recruitment of PAK1 were effectively inhibited by Fal-002-2. Fal-002-2 also blocked the activation of Rac1 and Cdc42 in a concentration range that effectively inhibited PAK activation. Taken together, these results suggest that Fal-002-2 inhibits fMLP-stimulated O2(•-) generation in neutrophils mainly through the blockade of PKC and PAK signaling pathways and partly through p38 MAPK signaling.
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Mitochondrial abnormalities in temporal lobe of autistic brain.
Neurobiol. Dis.
PUBLISHED: 01-10-2013
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Autism spectrum disorder (ASD) consists of a group of complex developmental disabilities characterized by impaired social interactions, deficits in communication and repetitive behavior. Multiple lines of evidence implicate mitochondrial dysfunction in ASD. In postmortem BA21 temporal cortex, a region that exhibits synaptic pathology in ASD, we found that compared to controls, ASD patients exhibited altered protein levels of mitochondria respiratory chain protein complexes, decreased Complex I and IV activities, decreased mitochondrial antioxidant enzyme SOD2, and greater oxidative DNA damage. Mitochondrial membrane mass was higher in ASD brain, as indicated by higher protein levels of mitochondrial membrane proteins Tom20, Tim23 and porin. No differences were observed in either mitochondrial DNA or levels of the mitochondrial gene transcription factor TFAM or cofactor PGC1?, indicating that a mechanism other than alterations in mitochondrial genome or mitochondrial biogenesis underlies these mitochondrial abnormalities. We further identified higher levels of the mitochondrial fission proteins (Fis1 and Drp1) and decreased levels of the fusion proteins (Mfn1, Mfn2 and Opa1) in ASD patients, indicating altered mitochondrial dynamics in ASD brain. Many of these changes were evident in cortical pyramidal neurons, and were observed in ASD children but were less pronounced or absent in adult patients. Together, these findings provide evidence that mitochondrial function and intracellular redox status are compromised in pyramidal neurons in ASD brain and that mitochondrial dysfunction occurs during early childhood when ASD symptoms appear.
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Association study of polymorphisms rs4552569 and rs17095830 and the risk of ankylosing spondylitis in a Taiwanese population.
PLoS ONE
PUBLISHED: 01-04-2013
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Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. However, the development of anklosing spondylitis is unclear. Human leukocyte antigens HLA-B27 and ERAP1 have been widely reported to be associated with AS susceptibility. A recent genome-wide association study (GWAS) showed that two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569) and within ANO6 at 12q12 (rs17095830) contribute to the risk of AS in Han Chinese. In this study, we enrolled 475 AS patients and 475 healthy subjects to assess whether these genetic variations contribute to the susceptibility and the severity of AS in the Taiwanese population. The correlation between genetic polymorphisms, AS activity indexes, (namely, BASDAI, BASFI and BAS-G) and AS complications (uveitis and inflammatory bowel disease) were tested using the markers, rs4552569 and rs17095830. Although no association between rs4552569/rs17095830 genetic polymorphisms and AS susceptibility/severity was found, a significant association between rs17095830 and inflammatory bowel disease was observed in a Taiwanese population.
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The outcomes of infantile vallecular cyst post CO? laser treatment.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 01-03-2013
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Vallecular cyst is not a common disease of neonate and infant. However, it may cause severe airway obstruction and even death. Its clinical symptoms are similar to laryngomalacia, including stridor, suprasternal retraction, substernal retraction, feeding difficulties, vomiting, failure to thrive, feeding choking and desaturation. This study is aimed to evaluate the surgical outcomes of infantile vallecular cyst post CO? laser treatment and to explore the appropriate time point of surgery for infantile vallecular cyst.
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Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling.
Cell. Mol. Life Sci.
PUBLISHED: 01-03-2013
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Protein activities controlled by receptor protein tyrosine phosphatases (RPTPs) play comparably important roles in transducing cell surface signals into the cytoplasm by protein tyrosine kinases. Previous studies showed that several RPTPs are involved in neuronal generation, migration, and axon guidance in Drosophila, and the vertebrate hippocampus, retina, and developing limbs. However, whether the protein tyrosine phosphatase type O (ptpro), one kind of RPTP, participates in regulating vertebrate brain development is largely unknown. We isolated the zebrafish ptpro gene and found that its transcripts are primarily expressed in the embryonic and adult central nervous system. Depletion of zebrafish embryonic Ptpro by antisense morpholino oligonucleotide knockdown resulted in prominent defects in the forebrain and cerebellum, and the injected larvae died on the 4th day post-fertilization (dpf). We further investigated the function of ptpro in cerebellar development and found that the expression of ephrin-A5b (efnA5b), a Fgf signaling induced cerebellum patterning factor, was decreased while the expression of dusp6, a negative-feedback gene of Fgf signaling in the midbrain-hindbrain boundary region, was notably induced in ptpro morphants. Further analyses demonstrated that cerebellar defects of ptpro morphants were partially rescued by inhibiting Fgf signaling. Moreover, Ptpro physically interacted with the Fgf receptor 1a (Fgfr1a) and dephosphorylated Fgfr1a in a dose-dependant manner. Therefore, our findings demonstrate that Ptpro activity is required for patterning the zebrafish embryonic brain. Specifically, Ptpro regulates cerebellar formation during zebrafish development through modulating Fgf signaling.
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Harmaline-induced tremor in mice: videotape documentation and open questions about the model.
Tremor Other Hyperkinet Mov (N Y)
PUBLISHED: 01-01-2013
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Harmaline-induced tremor in rodents has been extensively used as an animal model for essential tremor (ET). However, there is no visual documentation in the published literature.
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Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.
PLoS ONE
PUBLISHED: 01-01-2013
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The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-? (HIF1?) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1?, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1?- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1?, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.
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A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary artery lesion in Kawasaki disease.
PLoS ONE
PUBLISHED: 01-01-2013
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Single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC, rs28493229) and caspase-3 (CASP3, rs113420705) are associated with susceptibility to KD in Japanese and Taiwanese populations. This study was conducted to investigate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) resistance and coronary artery lesion (CAL) in Taiwanese population. A total of 340 KD patients were subjected to assess by the identification of 2-locus genes model. A combinatorial association between ITPKC (rs28493229) and CASP3 (rs113420705) was found in CAL formation (P?=?0.0227, OR: 3.06). KD patients with high-risk genotype had a trend of overrepresentation in IVIG resistance compared with individual SNPs. Our findings suggest the existence of genetic factors affecting patients risk for CAL formation and IVIG responsiveness in a Taiwanese population.
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Dietary uptake of Wedelia chinensis extract attenuates dextran sulfate sodium-induced colitis in mice.
PLoS ONE
PUBLISHED: 01-01-2013
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Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS)-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.