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1.
Transl Stroke Res ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37783839

ABSTRACT

Blood-brain barrier (BBB) disruption is a prominent pathophysiological mechanism in stroke. Transplantation of mesenchymal stem cells (MSCs) preserves BBB integrity following ischemic stroke. Fibroblast growth factor 21 (FGF21) has been shown to be a potent neuroprotective agent that reduces neuroinflammation and protects against BBB leakage. In this study, we assessed the effects of transplantation of MSCs overexpressing FGF21 (MSCs-FGF21) on ischemia-induced neurological deficits and BBB breakdown. MSCs-FGF21 was injected into the rat brain via the intracerebroventricular route 24 h after middle cerebral artery occlusion (MCAO) surgery. The behavioral performance was assessed using modified neurological severity scores and Y-maze tests. BBB disruption was measured using Evans blue staining, IgG extravasation, and brain water content. The levels of tight junction proteins, aquaporin 4, and neuroinflammatory markers were analyzed by western blotting and immunohistochemistry. The activity of matrix metalloproteinase-9 (MMP-9) was determined using gelatin zymography. At day-5 after MCAO surgery, intraventricular injection of MSCs-FGF21 was found to significantly mitigate the neurological deficits and BBB disruption. The MCAO-induced loss of tight junction proteins, including ZO-1, occludin, and claudin-5, and upregulation of the edema inducer, aquaporin 4, were also remarkably inhibited. In addition, brain infarct volume, pro-inflammatory protein expression, and MMP-9 activation were effectively suppressed. These MCAO-induced changes were only marginally improved by treatment with MSCs-mCherry, which did not overexpress FGF21. Overexpression of FGF21 dramatically improved the therapeutic efficacy of MSCs in treating ischemic stroke. Given its multiple benefits and long therapeutic window, MSC-FGF21 therapy may be a promising treatment strategy for ischemic stroke.

2.
Opt Express ; 30(16): 28470-28478, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-36299041

ABSTRACT

We demonstrate a real-time, reusable, and reversible integrated optical sensor for temperature monitoring within harsh environments. The sensor architecture combines the phase change property of chalcogenide glasses (ChG) with the high-density integration advantages of high index silicon waveguides. To demonstrate sensor feasibility, ChG composition Ge40S60, which is characterized by a sharp phase transition from amorphous to crystalline phase around 415 °C, is deposited over a 50 µm section of a single mode optical waveguide. The phase transition changes the behavior of Ge40S60 from a low loss to high loss material, thus significantly affecting the hybrid waveguide loss around the phase transition temperature. A transmission power drop of over 40dB in the crystalline phase compared to the amorphous phase is experimentally measured. Moreover, we recover the amorphous phase through the application of an electrical pulse, thus showing the reversible nature of our compact temperature sensor. Through integrating multiple compositions of ChG with well-defined phases transition temperatures over a silicon waveguide array, it is possible to determine, in real-time, the temperature evolution within a harsh environment, such as within a nuclear reactor cladding.

3.
J Pharm Biomed Anal ; 221: 115003, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36095885

ABSTRACT

The probable carcinogenic nitrosamine impurities, such as N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA), have been detected from various pharmaceuticals in recent years. The sensitive chromatographic methods, including liquid chromatography (LC) and gas chromatography (GC), have been applied for analyzing nitrosamines in the pharmaceutical substrates, such as sartans, ranitidine and metformin. In comparison of LC, the efficacy of GC for analyzing multiple nitrosamines in diverse pharmaceuticals will be limited or attenuated owing to the chemical properties of target analytes or matrix hinderance of pharmaceutical substrates. To extend the applicability of GC analysis for multiple nitrosamines in pharmaceuticals, this study presented a gas chromatograph tandem mass (GC-MS/MS) method for monitoring 14 nitrosamines within 44 pharmaceuticals, whereas the headspace-solid phase microextraction (HS-SPME) sampling mode was introduced. Chromatographic separation was achieved on a DB-heavyWax column (30 m × 0.25 mm; i.d., 0.25 µm), whereas the HS-SPME sampling mode with a 50/30 µm DVB/CAR/PDMS extracting fiber was applied for comparison of the direct injection mode. Meanwhile, the HS-SPME conditions were optimized to evaluate the effects of the parameters on analyzing total nitrosamines in pharmaceuticals by GC-MS/MS. The optimal conditions of HS-SPME were as follows: extracting solution of 90% NaCl, HS incubation time 1 min, SPME adsorbing at 80 â„ƒ for 30 min, and desorbing at 250 â„ƒ for 5 min. The limit of quantification (LOQ) for 14 nitrosamines in pharmaceutical matrices under the optimal conditions was 0.05 µg/g for the optimal HS-SPME, whereas the value was 0.05-0.25 µg/g for direct injection.


Subject(s)
Metformin , Nitrosamines , Angiotensin II Type 1 Receptor Blockers/analysis , Diethylnitrosamine/analysis , Dimethylnitrosamine/analysis , Gas Chromatography-Mass Spectrometry/methods , Metformin/analysis , Nitrosamines/analysis , Pharmaceutical Preparations , Ranitidine , Sodium Chloride , Solid Phase Microextraction/methods , Tandem Mass Spectrometry
4.
Forensic Sci Int ; 325: 110884, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34245937

ABSTRACT

New psychoactive substances are being launched in the drug market at a rapidly growing pace. More than 950 new psychoactive substances have been reported to the United Nations Office on Drugs and Crime. The development of new psychoactive substance abuse has drawn risks on public health and safety. Phenethylamines, along with other stimulants, accounted for the majority of the new psychoactive substances being reported in the past decade. This study presents a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous screening of 74 conventional and artificial phenethylamines in urine samples. The chromatographic analysis was performed by a direct dilute-and-shoot procedure using a Phenomenex Kinetex® Phenyl-Hexyl column (10 cm × 2.1 mm i.d., 1.7 µm) and two mobile phases (A: 0.1% formic acid aqueous solution with 5 mM ammonium acetate, B: 0.1% formic acid methanolic solution). The mass fragments were collected under the multiple reaction monitoring mode. The linearity range located in 1.0-50.0 ng/mL for quantitative analysis. The limit of detection and lower limit of quantification for 74 phenethylamines were 0.5 ng/mL and 1.0 ng/mL, respectively. The method was validated and further applied to analyze authentic urine samples. Twenty samples were tested positive of seven phenethylamines from 67 samples, whereas the contents detected were 9.8 ng/mL to 147.1 µg/mL with dilution factors of 40 to 20,000 folds.


Subject(s)
Illicit Drugs/urine , Phenethylamines/urine , Psychotropic Drugs/urine , Chromatography, Liquid , Humans , Reproducibility of Results , Substance Abuse Detection , Tandem Mass Spectrometry
5.
Forensic Sci Int ; 315: 110429, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32784041

ABSTRACT

Synthetic cathinones, which are a group of ß-keto analogs of phenethylamine, have been reported as the most emerging new psychoactive substances in the past decade. The quantity and variety of synthetic cathinones have continued to increase, which poses considerable risks to public health and social security. In this study, an analytical method based on liquid chromatography-tandem mass spectrometry (LCMS/MS) was established for the simultaneous determination of 73 synthetic cathinones and related metabolites in urine. The chromatographic analysis was performed using a Kinetex® Biphenyl column (10 cm ×2.1 mm, 1.7 µm), applying a gradient mobile phase, comprising 0.1 % formic acid aqueous solution with 5 mM ammonium acetate and 0.1 % formic acid methanolic solution; the entire run time of the analysis was within 8 min. The multiple reaction monitoring (MRM) mode was employed to collect the monitoring and quantitative ion pairs. Intra-day/inter-day precision and accuracy were less than 10 % for all the studied analytes. The limits of detection and quantification for all the analytes were 0.1-0.5 ng/mL and 0.5-1.0 ng/mL, respectively. The matrix effect was satisfactory for all the analytes, with a deviation lower than 20 %. The present method was further applied to 67 authentic urine samples in which 13 different synthetic cathinones were detected from 32 positive samples. The abuse of poly-synthetic cathinones was examined that up to seven items was detected in one case from authentic samples in this study.


Subject(s)
Alkaloids/urine , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Humans , Psychotropic Drugs/urine , Substance Abuse Detection/methods
6.
J Food Drug Anal ; 28(2): 292-301, 2020 Jun 15.
Article in English | MEDLINE | ID: mdl-35696119

ABSTRACT

An incident of sartan medicine contamination was notified by Europe in June 2018. The contaminant was identified as a probable carcinogenic nitrosamine and the recalls of sartan medicines were soon made. Since then, more nitrosamine contaminants in sartan medicines were reported. To broaden the applicability and variety in nitrosamine determination, a multi-analyte method is required. In this study, a feasible and sensitive multi-analyte LC-MS/MS method for determination of 12 nitrosamines in sartans was established, where the active pharmaceutical ingredients and final products merchandised in Taiwan were also examined. Chromatographic separation was achieved on an Xselect® HSS T3 column (15 cm × 3 mm i.d., 3.5 µm) with gradient elution using mobile phase A consisting of 0.1% formic acid in water and mobile phase B consisting of 0.1% formic acid in acetonitrile/methanol (2:8). Validation of the proposed method was also carried out. The limit of detection and limit of quantification for 12 nitrosamines were 20 ng/g and 50 ng/g, respectively. The intra-day and inter-day recoveries of nitrosamines were among 80-120% with precision of 20% for most nitrosamines within sartans matrices. The method was successfully established and applied to authentic samples which a total of 98 positive samples containing 5 distinct nitrosamines, including N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitroso-N-methyl-4-aminobutyric acid, N-nitrosomorpholine and N-nitrosopiperidine, were detected from 557 authentic samples.

7.
Brain Res ; 1720: 146301, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31226324

ABSTRACT

Although a good deal is known about the genetics and pathophysiology of Parkinson's disease (PD), and information is emerging about its cause, there are no pharmacological treatments shown to have a significant, sustained capacity to prevent or attenuate the ongoing neurodegenerative processes. However, there is accumulating clinical results to suggest that physical exercise is such a treatment, and studies of animal models of the dopamine (DA) deficiency associated with the motor symptoms of PD further support this hypothesis. Exercise is a non-pharmacological, economically practical, and sustainable intervention with little or no risk and with significant additional health benefits. In this study, we investigated the long-term effects of voluntary exercise on motor behavior and brain biochemistry in the transgenic MitoPark mouse PD model with progressive degeneration of the DA systems caused by DAT-driven deletion of the mitochondrial transcription factor TFAM in DA neurons. We found that voluntary exercise markedly improved behavioral function, including overall motor activity, narrow beam walking, and rotarod performance. There was also improvement of biochemical markers of nigrostriatal DA input. This was manifested by increased levels of DA measured by HPLC, and of the DA membrane transporter measured by PET. Moreover, exercise increased oxygen consumption and, by inference, ATP production via oxidative phosphorylation. Thus, exercise augmented aerobic mitochondrial oxidative metabolism vs glycolysis in the nigrostriatal system. We conclude that there are clear-cut physiological mechanisms for beneficial effects of exercise in PD.


Subject(s)
Parkinson Disease/metabolism , Physical Exertion/physiology , Animals , Biomarkers/metabolism , Corpus Striatum/drug effects , DNA-Binding Proteins/metabolism , Disease Models, Animal , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Dopaminergic Neurons/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mitochondria/metabolism , Motor Activity/physiology , Parkinson Disease/therapy , Substantia Nigra/drug effects , Transcription Factors/metabolism , Tyrosine 3-Monooxygenase/metabolism
8.
J Neurotrauma ; 36(7): 1054-1059, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30226403

ABSTRACT

Mild traumatic brain injury (mTBI) constitutes 75 ∼ 90% of all TBI cases and causes various physical, cognitive, emotional, and other psychological symptoms. Nogo receptor 1 (NgR1) is a regulator of structural brain plasticity during development and in adulthood. Here, we used mice that, in the absence of doxycycline, overexpress NgR1 in forebrain neurons (MemoFlex) to determine the role of NgR1 in recovery from mTBI with respect to balance, cognition, memory, and emotion. We compared wild-type (WT), MemoFlex, and MemoFlex + doxycycline mice to the same three groups subjected to mTBI. mTBI was induced by a controlled 30-g weight drop. We found that inability to downregulate NgR1 significantly impairs recovery from mTBI-induced impairments. When the NgR1 transgene was turned off, recovery was similar to that of WT mice. The results suggest that the ability to regulate NgR1 signaling is needed for optimal recovery of motor coordination and balance, spatial memory, cognition, and emotional functions after mTBI.


Subject(s)
Brain Concussion/metabolism , Cognition/physiology , Emotions/physiology , Nogo Receptor 1/metabolism , Postural Balance/physiology , Recovery of Function/physiology , Animals , Brain Concussion/physiopathology , Disease Models, Animal , Female , Male , Mice , Mice, Transgenic , Neurons/metabolism , Nogo Receptor 1/genetics , Prosencephalon/metabolism , Spatial Memory/physiology
9.
Medicine (Baltimore) ; 97(30): e11652, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30045316

ABSTRACT

The objective of this study was to reveal the relationships of mental health, social support, health-related quality of life (HRQOL) as well as their dimensions in HIV-positive men who have sex with men (MSM).HIV-positive MSM were interviewed by a cross-sectional study design using the world Health Organization quality of life bref scale, social support rating scale, and self-rated anxiety and depression scales. Canonical correlation analysis and structural equation model (SEM) were utilized to analyze to the collected data.Three first pair of canonical variables that was statistically significant (P < .0001) and verified could account for the largest cumulative proportion were computed from canonical correlation analysis. The results showed, among the dimensions, depression and anxiety were negatively correlated with support utilization and physical health, while subjective support and support utilization were positively correlation with social relationship health. Structural equation model results showed that support utilization (0.632, T = 10.44), depression (0.816, T = 20.37), and environmental dimension (0.833, T = 38.47) had the largest standardized factor loading in social support, mental health, and HRQOL. The structural coefficient between social support and mental health was -0.433 (T = -5.88), between mental health and HRQOL was -0.592 (T = -10.33), between social support and HRQOL was 0.290 (T = 4.10), indicated social support not only exerted a direct influence, but also mediated mental health to have an indirect effect on HRQOL for HIV-positive MSM.Environmental dimension is the foremost factor of HRQOL for HIV-positive MSM. Alleviating anxiety symptoms maybe improve physical health, while promoting the support utilization is an effective measure of alleviating depression and improving social relationship health for this special group.


Subject(s)
HIV Seropositivity/psychology , Homosexuality, Male/psychology , Mental Health , Quality of Life/psychology , Social Support , Adult , Anxiety/etiology , Cross-Sectional Studies , Depression/etiology , Humans , Male
10.
Enzyme Microb Technol ; 86: 34-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26992790

ABSTRACT

An approach was developed to enhance the efficiency for the bioconversion of 1-(3-hydroxyphenyl)-2-(methyamino)-ethanone to (R)-phenylephrine. The strain Serratia marcescens N10612, giving the benefit of 99% enantiomeric excess in (R)-PE conversion, was used. The fermentation was devised to harvest cells with high hydrophobic prodigiosin content inside the cells. Then, the partial acetone extraction was applied to remove prodigiosin from the cells. The treatment was found to increase the cells conversion rate without loss of the cells NADPH redox system. When using 50% (v/v) acetone for 5min, the processed cells can give a specific conversion rate of 16.03µmol/h/g-cells. As compared the treated cells with cells under the basal medium, the maximum reaction rate (Vmax) increased from 6.69 to 10.27 (µmol/h/g-cells), the dissociation constant (Km) decreased from 0.236 to 0.167mM and the substrate inhibition constant (KSi) increased from 0.073 to 1.521mM. The 20-fold increase in substrate inhibition constant referred to a great release from the substrate inhibition for the use of S. marcescens N10612 in the bioconversion, which would greatly benefit the bioconversion to be industrialized.


Subject(s)
Phenylephrine/metabolism , Acetone/pharmacology , Biocatalysis , Biotransformation/drug effects , Fermentation , Hydrophobic and Hydrophilic Interactions , Kinetics , NADP/metabolism , Oxidation-Reduction , Phenylephrine/chemistry , Prodigiosin/metabolism , Serratia marcescens/drug effects , Serratia marcescens/metabolism , Stereoisomerism
11.
Ultrason Sonochem ; 26: 415-421, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25691009

ABSTRACT

The strain Serratia marcescens N10612 is used to perform the bioconversion of 1-(3-hydroxyphenyl)-2-(methyamino)-ethanone (HPMAE) to (R)-phenylephrine ((R)-PE), which is an ephedrine drug substitute. The use of an ultrasound approach is found to improve the efficiency of the (R)-PE bioconversion. The optimization of the (R)-PE bioconversion is carried out by means of statistical experiment design. The optimal conditions obtained are 1.0mM HPMAE, 18.68 g/L glucose and ultrasound power of 120 W, where the predicted specific rate of the (R)-PE bioconversion is 31.46 ± 2.22 (ìmol/h/g-cells) and the experimental specific rate is 33.27 ± 1.46 (ìmol/h/g-cells), which is 3-fold higher than for the operation under ultrasound power of 200 W (11.11 ìmol/h/g-cells) and 4.3-fold higher than for the shaking operation (7.69 ìmol/h/g-cells). The kinetics study of the bioconversion also shows that under the ultrasound operation, the optimal rate (Vmax) of the (R)-PE bioconversion increases from 7.69 to 11.11 (µmol/h/g-cells) and the substrate inhibition constant (KSi) increases from 1.063 mM for the shaking operation to 1.490 mM for ultrasound operation.


Subject(s)
Phenylephrine/chemistry , Phenylephrine/metabolism , Serratia marcescens/cytology , Serratia marcescens/metabolism , Ultrasonic Waves , Biotransformation , Kinetics , Stereoisomerism
12.
J Biosci Bioeng ; 116(5): 562-6, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23764018

ABSTRACT

In this study, the cell surface expression system was the first time used to directly produce extracellular enzyme. In the plasmid construction, the truncated ice nucleation protein (INP) was fused with intein (INT) and target protein, D-hydantoinase (DHTase), to form the INP-INT-DHTase gene. The plasmid containing this gene was transformed into Escherichia coli ER2566 cells. The gene construct enables the expression of INP-INT-DHTase fusion protein, which might anchor on cell membrane surface. The induction conditions were studied and optimal conditions were as follows: E. coli ER2566 was incubated at 37°C and 200 rpm till OD600 reached 0.6. Then, 0.05 mM IPTG was added and the induction was conducted at 15°C for 24 h. The cell was harvested and resuspended in the cleavage buffer (50 mM Tris-HCl buffer, pH 6). The cleavage reaction was carried out at 25°C, and 100 rpm for 24 h. The DHTase with an activity of 0.225 U/ml and a purity of 63.2% was obtained via centrifugation. This study demonstrated the feasibility of direct extracellular enzyme production using E. coli via only two steps of centrifugation.


Subject(s)
Amidohydrolases/isolation & purification , Amidohydrolases/metabolism , Extracellular Space/enzymology , Recombinant Fusion Proteins/biosynthesis , Amidohydrolases/biosynthesis , Amidohydrolases/genetics , Bacterial Outer Membrane Proteins/genetics , Bacterial Outer Membrane Proteins/metabolism , Biocatalysis , Brevibacillus/enzymology , Centrifugation , Enzyme Induction , Escherichia coli/genetics , Feasibility Studies , Inteins/genetics , Intracellular Space/enzymology , Isopropyl Thiogalactoside , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/isolation & purification , Recombinant Fusion Proteins/metabolism , Salts , Temperature
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