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1.
ChemistryOpen ; : e202400041, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619325

ABSTRACT

Lithium-ion secondary batteries (LIB) with high energy density have attracted much attention for electric vehicle (EV) applications. However, LIBs have a safety problem because these batteries contain a flammable organic electrolyte. As such, all-solid secondary batteries that are not flammable have been extensively reported recently. In this study, we have focused on polymer electrolytes, which is flexible and is expected to address the safety problem. However, the conventional polymer electrolytes have low electrial conductivity at room temperature. Various attempts have been made to solve this problem, such as the addition of inorganic fillers and ionic liquids; however, these composite polymer electrolytes have not yet reached a practical level of lithium-ion conductivity. In this study, high electrical conductivity and lithium dendrite formation-free PEO based composite electrolytes are developed with both a filler of Li6,4La3Zr1.4Ta0.6O12 and liquid plasticizers of tetraethylene glycol dimethyl ether and 1,2 dimethoxyethane. The proposed flexible polymer electrolyte shows a high electrical conduciviy of 6.01×10-4 S cm-1 at 25 °C.

2.
Case Rep Oncol ; 16(1): 705-710, 2023.
Article in English | MEDLINE | ID: mdl-37936662

ABSTRACT

Although osimertinib is a key drug in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, the safety in hemodialysis patients has not been established. A 76-year-old man was diagnosed with NSCLC with EGFR deletion mutation in exon 19. After treatment failure with first- and second-generation EGFR tyrosine kinase inhibitors, a T790M mutation was revealed by liquid biopsy. Hemodialysis was started three times a week because chronic renal failure worsened during treatment. Although the subsequent administration of osimertinib (80 mg daily) resulted in a tumor shrinkage and a gradual increase in the plasma concentration of osimertinib, which resulted in grade 3 general fatigue, reducing the dosage of osimertinib decreased its plasma concentration, leading to an improvement in his adverse event. Subsequently, with by adjusting the dosage while periodically measuring the plasma concentration of osimertinib, a stable therapeutic effect was sustained over the long term with no symptoms. Periodic plasma concentration measurements may be indispensable for successful treatment with osimertinib in hemodialysis patients.

3.
J Neurochem ; 163(5): 375-390, 2022 12.
Article in English | MEDLINE | ID: mdl-36227633

ABSTRACT

Phosphacan, a chondroitin sulfate proteoglycan, is a repulsive cue of cerebellar granule cells. This study aims to explore the molecular mechanism. The glycosylphosphatidylinositol-anchored neural adhesion molecule TAG-1 is a binding partner of phosphacan, suggesting that the repulsive effect of phosphacan is possibly because of its interaction with TAG-1. The repulsive effect was greatly reduced on primary cerebellar granule cells of TAG-1-deficient mice. Surface plasmon resonance analysis confirmed the direct interaction of TAG-1 with chondroitin sulfate C. On postnatal days 1, 4, 7, 11, 15, and 20 and in adulthood, phosphacan was present in the molecular layer and internal granular layer, but not in the external granular layer. In contrast, transient TAG-1 expression was observed exclusively within the premigratory zone of the external granular layer on postnatal days 1, 4, 7, and 11. Boyden chamber cell migration assay demonstrated that phosphacan exerted its repulsive effect on the spontaneous and brain-derived neurotrophic factor (BDNF)-induced migration of cerebellar granule cells. The BDNF-induced migration was inhibited by MK-2206, an Akt inhibitor. The pre-treatment with a raft-disrupting agent, methyl-ß-cyclodextrin, also inhibited the BDNF-induced migration, suggesting that lipid rafts are involved in the migration of cerebellar granule cells. In primary cerebellar granule cells obtained on postnatal day 7 and cultured for 7 days, the ganglioside GD3 and TAG-1 preferentially localized in the cell body, whereas the ganglioside GD1b and NB-3 localized in not only the cell body but also neurites. Pre-treatment with the anti-GD3 antibody R24, but not the anti-GD1b antibody GGR12, inhibited the spontaneous and BDNF-induced migration, and attenuated BDNF-induced Akt activation. These findings suggest that phosphacan is responsible for the repulsion of TAG-1-expressing cerebellar granule cells via GD3 rafts to attenuate BDNF-induced migration signaling.


Subject(s)
Cell Adhesion Molecules, Neuronal , Receptor-Like Protein Tyrosine Phosphatases, Class 5 , Animals , Mice , Rats , Brain-Derived Neurotrophic Factor/metabolism , Cell Adhesion Molecules, Neuronal/metabolism , Cerebellum/metabolism , Membrane Microdomains/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor-Like Protein Tyrosine Phosphatases, Class 5/metabolism
4.
Antibiotics (Basel) ; 11(7)2022 Jul 21.
Article in English | MEDLINE | ID: mdl-35884236

ABSTRACT

The bacterium Pseudomonas aeruginosa is known to be associated with nosocomial infections around the world. Pazufloxacin, a potent DNA gyrase inhibitor, is known to be an effective drug candidate. However, it has not been clarified whether the pharmacokinetic (PK)/pharmacodynamic (PD) of pazufloxacin was effective against P. aeruginosa. Herein, we demonstrated that the PK/PD index of pazufloxacin against P. aeruginosa infection is used to optimize the dosing regiments. We constructed an in vivo infection model by infecting P. aeruginosa into the thigh of a mouse to determine the PD, and we measured the serum concentration of pazufloxacin to construct the PK model using high-performance liquid chromatography. The therapeutic efficacy of pazufloxacin was correlated with the ratio of the area under the free concentration time curve at 24 h to the minimum inhibitory concentration (fAUC24/MIC), and the maximum free concentration to the MIC (fCmax/MIC). Each contribution rate (R2) was 0.72 and 0.65, respectively, whereas the time at which the free drug concentration remained above the MIC (R2 = 0.28). The target value of pazufloxacin fAUC24/MIC for stasis was 46.1, for 1 log10 it was 63.8, and for 2 log10 it was 100.8. Moreover, fCmax/MIC for stasis was 5.5, for 1 log10 it was 7.1, and for 2 log10 it was 10.8. We demonstrated that the in vivo concentration-dependent activity of pazufloxacin was effective against the P. aeruginosa infection, and successfully made the PK/PD model sufficiently bactericidal. The PK/PD model will be beneficial in preventing the spread of nosocomial infections.

5.
Cancers (Basel) ; 13(14)2021 Jul 08.
Article in English | MEDLINE | ID: mdl-34298637

ABSTRACT

Afatinib is used to treat non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation as a second-generation EGFR-tyrosine kinase inhibitor (TKI). Early prediction of adverse effects based on the pharmacokinetics of afatinib enables support for quality of life (QOL) in patients with no change in efficacy. We examined the pharmacokinetic relationship between trough plasma concentration and adverse effects and evaluated the utility of measuring the trough plasma concentration of afatinib as the first EGFR-TKI treatment for NSCLC in a prospective multicenter study. Twenty-four patients treated with afatinib were enrolled in this study. All blood samples were collected at the trough point, and plasma concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. Logistic regression analysis for the dose reduction of afatinib was performed, and the receiver operating characteristic (ROC) curve was plotted. Although all patients started afatinib at 40 mg/day, plasma concentrations were variable, and mean and median trough plasma concentrations were 32.9 ng/mL and 32.5 ng/mL in this study, respectively. Minimum and maximum trough plasma concentrations were 10.4 ng/mL and 72.7 ng/mL, respectively. This variability was speculated to involve personal parameters such as laboratory data. However, no patient characteristics or laboratory data examined correlated with the trough plasma concentration of afatinib, except albumin. Albumin showed a weak correlation with plasma concentration (r = 0.60, p = 0.009). The trough plasma concentration of afatinib was significantly associated with the dose reduction of afatinib (p = 0.047). The area under the ROC curve (AUC) for the trough plasma concentration of afatinib was 0.81. The cut-off value was 21.4 ng/mL. The sensitivity and specificity of the cut-off as a risk factor were 0.80 and 0.75. In summary, the trough plasma concentration of afatinib was associated with continued or reduced dosage because of the onset of several adverse effects, and a threshold was seen. Adverse effects not only lower QOL but also hinder continued treatment. Measuring plasma concentrations of afatinib appears valuable to predict adverse effects and continue effective therapy.

6.
Biol Pharm Bull ; 44(5): 732-736, 2021.
Article in English | MEDLINE | ID: mdl-33952829

ABSTRACT

Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL = 6.5 ± 4.0 L/h, Vd = 19.3 ± 0.2 L, Ke = 0.4 ± 0.2, and t1/2 = 2.7 ± 1.6 h. The most correlated renal function index was estimated glomerular filtration rate (eGFRcys-c) calculated by serum cystatin-c (r = 0.7374, correlation formula; CL of ampicillin = 0.1937 × eGFRcys-c-0.6726). Based on this formula, we calculated the clearance of ampicillin and developed dosing regimens for the elderly. Serum cystatin-c concentration is an ideal index to optimize ampicillin-sulbactam antimicrobial therapy in elderly patients with pneumonia.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cystatin C/blood , Pneumonia/drug therapy , Aged , Aged, 80 and over , Aging/physiology , Ampicillin/administration & dosage , Ampicillin/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Dose-Response Relationship, Drug , Drug Dosage Calculations , Female , Glomerular Filtration Rate/physiology , Humans , Kidney/physiology , Male , Models, Biological , Pneumonia/blood , Renal Elimination , Sulbactam/administration & dosage , Sulbactam/pharmacokinetics
7.
J Glob Antimicrob Resist ; 24: 83-87, 2021 03.
Article in English | MEDLINE | ID: mdl-33290889

ABSTRACT

OBJECTIVES: Pharmacokinetic/pharmacodynamic (PK/PD) analysis using murine infection models is a well-established methodology for optimising antimicrobial therapy. Therefore, we investigated the PK/PD indices of teicoplanin againstStaphylococcus aureus using a murine thigh infection model. METHODS: Mice were rendered neutropenic by administration of a two-step dosing of cyclophosphamide. Then, isolates of methicillin-susceptibleS. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) were inoculated into the thighs of neutropenic mice. PK/PD analyses were performed by non-linear least-squared regression using the MULTI program. RESULTS: Target values offCmax/MIC (r2 = 0.94) of teicoplanin for static effect and 1 log10 kill against MSSA were 4.44 and 15.44, respectively. Target values of fAUC24/MIC (r2 = 0.92) of teicoplanin for static effect and 1 log10 kill against MSSA were 30.4 and 70.56, respectively. Target values of fCmax/MIC (r2 = 0.91) of teicoplanin for static effect and 1 log10 kill against MRSA were 8.92 and 14.16, respectively. Target values of fAUC24/MIC (r2 = 0.92) of teicoplanin for static effect and 1 log10 kill against MRSA were 54.8 and 76.4, respectively. CONCLUSION: These results suggest thatfCmax/MIC and fAUC24/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcus aureus , Animals , Mice , Microbial Sensitivity Tests , Teicoplanin/pharmacology , Thigh
8.
RSC Adv ; 10(30): 17805-17815, 2020 May 05.
Article in English | MEDLINE | ID: mdl-35515630

ABSTRACT

The effects of mechanical uniaxial pressure and deflection of the separator on the electrochemical deposition of lithium metal were investigated. Instead of dendritic lithium growth without pressure, a much more dense and compact deposition can be achieved when pressure is applied to the cells during the lithium deposition process. This morphology is due to the formation of granular lithium followed by the generation of new lithium nuclei on the cathode surface. The improved lithium plating/stripping behavior in the cells under mechanical pressure yielded a 10% higher coulombic efficiency than cells without pressure. However, the cycle life is shortened with pressures higher than 1.39 MPa; therefore, there is an upper limit for improvement of the electrochemical characteristics near 1.39 MPa. The morphology of electrodeposited lithium becomes flatter with a large amount of electrodeposition under pressure when the number of polyethylene separators is increased to five due to the increase in the stiffness of the layered separators. Furthermore, high coulombic efficiency cycling by pressurization was increased to twice that for one separator sheet. Application of the optimal strength pressure and use of more inflexible separators are thus effective methods to control the microscopic morphology of electrodeposited lithium and improve the cycle performance of the lithium metal anode.

9.
Biol Pharm Bull ; 42(11): 1953-1956, 2019.
Article in English | MEDLINE | ID: mdl-31685778

ABSTRACT

Novel bivalent twin-drug type hydantoin derivatives were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the 5-substituted hydantoin derivatives (1a-b and 2a-d) examined in this study, bivalent symmetrical 5-substituted hydantoin derivative 1b showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of anti-proliferative activity (IC50) of this hydantoin derivative against the two cell lines (U251 and KB3-1) were 0.46 and 5.21 µM, respectively. The anti-proliferative activity of all of the compounds except for compounds 2a and 2d against U251 cells was higher than that of cisplatin. Bivalent symmetrical compound 1b had a biphenylmethane linker in the molecule. All of the tested bivalent hydantoin derivatives showed higher activity against U251 cells than against KB3-1 cells. For twin-drug type hydantoin derivatives 2a-d, which have a linear methylene linker in the molecules, it was found that methylene linker length in these molecules have an effect on the anti-proliferative activity against U251 and KB3-1 cells.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Hydantoins/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Humans , Hydantoins/chemistry , Molecular Structure
10.
Anticancer Res ; 39(8): 4129-4136, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31366497

ABSTRACT

BACKGROUND/AIM: 5-Aza-2-deoxycytidine (5-Aza-CdR) enhances the sensitivity to 5-fluorouracil (5-FU), but the molecular mechanism is not fully understood. The aim of this study was to investigate the molecular mechanism that enhances the sensitivity to 5-FU treated with 5-Aza-CdR via thymidine phosphorylase (TP). MATERIALS AND METHODS: The sensitivity to drugs was determined on several cancer cell lines by the MTT assay. Protein and mRNA levels were examined by immunoblot and RT-PCR, respectively. Gene silencing, binding of Sp1 to DNA and methylation of DNA was performed by siRNA, ChIP assay and sodium bisulfate genomic sequencing, respectively. RESULTS: Sp1-binding sites in the TP promoter were methylated in epidermoid carcinoma. 5-Aza-CdR demethylated Sp1-binding sites and enhanced sensitivity to 5-FU. CONCLUSION: Demethylation of Sp1-binding sites by 5-Aza-CdR was a key factor enhancing 5-FU sensitivity, which may enable more effective treatments for cancer patients with the combination of 5-Aza-CdR and 5-FU.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , DNA Methylation/genetics , Drug Resistance, Neoplasm/genetics , Sp1 Transcription Factor/genetics , Thymidine Phosphorylase/genetics , Binding Sites/drug effects , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , DNA Methylation/drug effects , DNA-Binding Proteins/genetics , Decitabine/metabolism , Fluorouracil/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Gene Silencing , Humans , Promoter Regions, Genetic/drug effects , RNA, Messenger/genetics , Thymidine Phosphorylase/chemistry
11.
Chem Commun (Camb) ; 55(52): 7454-7457, 2019 Jul 04.
Article in English | MEDLINE | ID: mdl-31184356

ABSTRACT

This study investigates oxygen electrocatalytic activities of perovskite-related compounds using a rotating disk electrode technique in an aqueous solution containing lithium chloride and lithium hydroxide. A hydrated oxyhydroxide Ruddelesden-Popper phase, Sr3Co2O5(OH)2·2H2O, exhibits excellent performance especially in the oxygen evolution reaction.

12.
Biol Pharm Bull ; 42(5): 833-836, 2019.
Article in English | MEDLINE | ID: mdl-31061327

ABSTRACT

Derivatives of C2-symmetrical bivalent phenylboronic acid exhibit several remarkable biological activities such as anti-herpes simplex virus (HSV)-1 and cytotoxic activities against Vero cells and they can reverse the effect of anticancer drugs. Novel symmetrical bivalent molecules were synthesized and their biological activities were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the tested compounds (1a-i), bivalent C2-symmetrical phenylboronic acid derivative 1g showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of 50% anti-proliferative activity (IC50) of this compound against the two cell lines (U251 and KB3-1) were 19.0 and 3.78 µM, respectively. The anti-proliferative activity of compound 1g towards KB3-1 cells was higher than that of cisplatin. The bivalent C2-symmetrical compound 1g had a linear methylene linker in the molecule.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Boronic Acids/pharmacology , Animals , Brain Neoplasms , Cell Line, Tumor , Cell Survival/drug effects , Chlorocebus aethiops , Glioma , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/growth & development , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/growth & development , Humans , Microbial Sensitivity Tests , Vero Cells
13.
Pediatr Int ; 61(6): 558-565, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30963629

ABSTRACT

BACKGROUND: Fatal adverse effects or relapse can occur with excessive or insufficient busulfan exposure in hematopoietic stem cell transplantation. Given that busulfan is mainly metabolized by glutathione S-transferase (GST), we investigated the influence of GST polymorphisms on busulfan pharmacokinetics in Japanese pediatric patients. METHODS: Blood samples were taken from patients receiving high-dose i.v. busulfan as the first dose. Plasma busulfan concentration was measured using high-performance liquid chromatography. The area under the plasma busulfan concentration-time curve (AUC) was calculated. The genotype of GSTA1 was determined on polymerase chain reaction (PCR)-restriction fragment length polymorphism. Multiplex PCR was used to detect the presence or absence of GSTM1 and GSTT1 in the genomic DNA samples. RESULTS: Twenty patients were consecutively enrolled. Phenotype prediction was defined as follows: poor metabolizer (n = 4), one or more GSTA1*B haplotype or GSTM1/GSTT1 double-null genotypes; and extensive metabolizer (n = 16), other genotypes. GSTA1, M1, and T1 independently had no significant differences in AUC0-∞ , clearance or elimination rate constant. For the infant with unexpectedly high AUC0-∞ (2,591 µmol/L min), the GSTA1, M1, and T1 polymorphisms were wild type. On further analysis, the poor metabolizer group had lower clearance and higher AUC0-∞, except for the aforementioned patient, compared with the extensive metabolizer group (1,531 vs 1,010 µmol/L min; P < 0.01). CONCLUSIONS: GST polymorphisms may have affected busulfan pharmacokinetics, but these effects were obscured by other factors, such as underlying disease, systemic conditions, treatment history, and race.


Subject(s)
Busulfan/pharmacokinetics , Glutathione Transferase/genetics , Immunosuppressive Agents/pharmacokinetics , Polymorphism, Restriction Fragment Length , Adolescent , Area Under Curve , Busulfan/administration & dosage , Busulfan/toxicity , Child , Child, Preschool , Chromatography, Liquid , Dose-Response Relationship, Drug , Female , Genetic Markers , Genotype , Hematopoietic Stem Cell Transplantation , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/toxicity , Infant , Japan , Male , Multiplex Polymerase Chain Reaction , Phenotype , Prospective Studies
15.
Am J Gastroenterol ; 114(1): 71-79, 2019 01.
Article in English | MEDLINE | ID: mdl-30315306

ABSTRACT

OBJECTIVES: In order to screen for gastric cancer effectively, its interval should be set according to the risk. This study aimed to determine whether risk stratification is possible using the data obtained from medical examination or endoscopic findings. METHODS: First, subjects who underwent both cancer screening and medical examination from 2009 to 2015 and underwent cancer screening once more by 2016 were studied. Data such as the lipid profile and history of smoking obtained during the medical examination, and the grade of atrophy and presence of peptic ulcers were studied using multivariate analysis. Next, subjects who underwent cancer screening twice or more between 2009 and 2015 with or without medical examinations were studied to analyze any correlation between the grade of atrophy and cancer occurrence using univariate analysis. In both studies, the status of Helicobacter pylori (HP) infection was determined. RESULTS: In the multivariate analysis, 9378 subjects were included. Aging, advanced atrophy, presence of ulcers, and uric acid levels were identified as risk factors. Among subjects who underwent successful HP eradication therapy, advanced atrophy and aging were observed to be crucial risk factors. In the univariate analysis, there were 12,941 subjects. Gastric cancer occurred more frequently in the more severe atrophy group (P < 0.001). The annual rate of cancer occurrence in the most severe atrophy group was 0.31%, which was approximately thrice as that in the less atrophy group. CONCLUSIONS: Risk stratification was possible based on endoscopic examination alone. The interval should be set depending on each case.


Subject(s)
Gastritis, Atrophic/epidemiology , Helicobacter Infections/epidemiology , Helicobacter pylori/isolation & purification , Stomach Neoplasms/epidemiology , Adult , Aged , Female , Gastritis, Atrophic/diagnostic imaging , Gastritis, Atrophic/microbiology , Gastritis, Atrophic/pathology , Gastroscopy , Helicobacter Infections/diagnostic imaging , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Humans , Japan/epidemiology , Male , Middle Aged , Neoplasm Grading , Risk Factors , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology
16.
Oncol Lett ; 15(6): 9929-9933, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29928366

ABSTRACT

Cancer stem-like cells (CSCs), which possess the ability to self-renewal and are multipotent, are regarded as the cause of tumor formation, recurrence, metastasis and drug resistance. It is necessary to understand the properties of CSCs in order to treat them effectively. It has been previously reported that S100 family proteins, which carry calcium-binding EF-hand motifs and are associated with tumorigenic processes, serve crucial roles in maintaining cancer stem-like properties. S100A16 is upregulated in various types of cancer, including bladder, lung and pancreatic. However, the roles of S100A16 in cancer cells, particularly CSCs, are not clear. The present study investigated the roles of S100A16 in CSCs using the sphere formation assay of Yumoto cells, which are a human cervical carcinoma cell line. The mRNA expression levels were evaluated by reverse transcription-polymerase chain reaction and the protein expression levels were detected by western blot analysis. Following the sphere formation of Yumoto cells, the mRNA and protein expression level of Oct4, Nanog and S100A16 were increased compared with the control cells. Following transfection with S100A16 small interfering RNA (siRNA), the mRNA and protein expression of Oct4 and Nanog were decreased and the spheroid size was significantly decreased in the sphere formation of Yumoto cells compared with control siRNA treated cells. There was no change in the p53 mRNA expression level, whereas the p53 protein expression level, which was decreased by the sphere formation, was recovered by S100A16 knockdown. In addition, the protein expression levels of Oct4 and Nanog, which were increased in the sphere formation, were decreased by the proteasome inhibitor lactacystin. No differences were observed in the S100A16 protein expression between the presence or absence of lactacystin. These results suggest that S100A16 serves an important role in the CSCs of human cervical carcinoma and is a positive regulator of Oct4 and Nanog.

17.
ACS Omega ; 3(5): 5558-5562, 2018 May 31.
Article in English | MEDLINE | ID: mdl-31458759

ABSTRACT

High-energy-density rechargeable batteries with performance beyond that of lithium-ion batteries are required for next-generation electric vehicles. We propose a novel rechargeable battery with a lithium anode and a NiCl2 aqueous cathode that is separated Li1.4Al0.4Ge0.2Ti1.4(PO4)3 as a water-stable lithium-ion-conducting solid electrolyte. The cell was discharged up to 93% of the theoretical cathode capacity at 0.5 mA cm-2 and 25 °C. The calculated energy density, based on the weights of NiCl2 and Li, and the average discharge voltage of 2.4 V at 0.5 mA cm-2, was 852 Wh kg-1, which is more than twice as high as that of conventional lithium-ion batteries. The cell was successfully cycled for 50 cycles without any degradation of the charge and discharge voltages at 0.5 mA cm-2 and 25 °C for 5 h charge and 5 h discharge, where the utilization of NiCl2 was 80%.

18.
Nat Commun ; 8: 15106, 2017 04 25.
Article in English | MEDLINE | ID: mdl-28440299

ABSTRACT

Reversible dendrite-free low-areal-capacity lithium metal electrodes have recently been revived, because of their pivotal role in developing beyond lithium ion batteries. However, there have been no reports of reversible dendrite-free high-areal-capacity lithium metal electrodes. Here we report on a strategy to realize unprecedented stable cycling of lithium electrodeposition/stripping with a highly desirable areal-capacity (12 mAh cm-2) and exceptional Coulombic efficiency (>99.98%) at high current densities (>5 mA cm-2) and ambient temperature using a diluted solvate ionic liquid. The essence of this strategy, that can drastically improve lithium electrodeposition kinetics by cyclic voltammetry premodulation, lies in the tailoring of the top solid-electrolyte interphase layer in a diluted solvate ionic liquid to facilitate a two-dimensional growth mode. We anticipate that this discovery could pave the way for developing reversible dendrite-free metal anodes for sustainable battery chemistries.

19.
PLoS One ; 11(7): e0157198, 2016.
Article in English | MEDLINE | ID: mdl-27388444

ABSTRACT

PURPOSE: This study aimed to evaluate predictive factors involved in efficacy and safety in Japanese infants who received theophylline therapy to prevent apnea of prematurity (AOP) after weaning from mechanical ventilation. METHODS: We retrospectively reviewed the medical records of infants who were administered intravenous aminophylline (theophylline ethylenediamine) for AOP at the neonatal intensive care unit, Kagoshima University Hospital, Japan, between January 2009 and June 2013. RESULTS: A total of 100 infants were evaluated as two separate groups in terms of efficacy and safety of theophylline. Sixty-seven (67.0%) infants had effective theophylline therapy. Multivariate logistic regression analysis showed that gestational age at birth was significant, with an odds ratio of 0.59 (p < 0.001). Receiver operating characteristic analysis showed that the cut-off value was 31.1 weeks old for predicting the efficacy of theophylline (specificity, 66.7%; sensitivity, 86.6%; p < 0.001; area under the curve, 0.750; 95% confidence interval, 0.45-0.74). Adverse reactions were identified in 21 (21.0%) infants. Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01). CONCLUSIONS: Physicians need to be aware of the possibility that theophylline fails to produce therapeutic effects for extubation in infants aged less than 31.1 weeks old, and adverse reactions can easily develop when theophylline is administered soon after birth.


Subject(s)
Airway Extubation , Apnea/drug therapy , Infant, Premature, Diseases/drug therapy , Theophylline/therapeutic use , Apnea/prevention & control , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/prevention & control , Intensive Care, Neonatal , Japan , Male , Multivariate Analysis , Odds Ratio , ROC Curve , Respiration, Artificial , Retrospective Studies , Theophylline/administration & dosage
20.
Am J Health Syst Pharm ; 73(14): 1077-86, 2016 Jul 15.
Article in English | MEDLINE | ID: mdl-27189856

ABSTRACT

PURPOSE: The processes used to revise the 2008 Basel Statements on the future of hospital pharmacy are summarized, and the revised statements are presented. METHODS: The process for revising the Basel Statements followed an approach similar to that used during their initial development. The Hospital Pharmacy Section (HPS) of the International Pharmaceutical Federation (FIP) revised the 2008 FIP Basel Statements in four phases, including a survey of hospital pharmacists worldwide, an internal review, online forums, and a face-to-face "World Café" workshop in Bangkok, Thailand. RESULTS: The global survey on the initial Basel Statements included input from 334 respondents from 62 countries. The majority of respondents agreed that most of the initial Basel Statements were acceptable as written and did not require revision. In total, 11 statements were judged by more than 10% of respondents as needing revision or deletion. The FIP HPS executive committee used the survey results to develop 69 initial revised draft statements. After an online discussion with the international hospital pharmacy community, including individuals from 28 countries representing all six World Health Organization regions, a final set of draft statements was prepared for the live discussion involving participants from 20 countries. The final 65 revised Basel Statements were voted on and accepted. CONCLUSION: Systematic revision of the FIP Basel Statements resulted in an updated reflection of aspirational goals for the future of hospital pharmacy practice. While this revision reflects the development of new goals for hospital pharmacy practice, the core principles of the Basel Statements remain an essential foundation for the discipline.


Subject(s)
Internationality , Pharmacy Service, Hospital/standards , Pharmacy Service, Hospital/trends , Societies, Pharmaceutical/standards , Societies, Pharmaceutical/trends , Congresses as Topic/trends , Forecasting , Humans , Surveys and Questionnaires , Switzerland , Thailand
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