Jen-Ai Lee

Taipei Medical University | TMU · School of Pharmacy

For the highly-selective analysis of lactic acid (LA), 2-hydroxybutyric acid (2HB), 3-hydroxybutyric acid (3HB) and malic acid (MA) enantiomers in human physiological fluids, a three-dimensional (3D) HPLC method following the fluorescence derivatization with 4-nitro-7-piperazino-2,1,3-benzoxadiazole has been designed and developed. The 3D-HPLC syst...

Optical activity and its relation to molecular chirality are significant in the measurement of optical rotation or circular dichroism characteristics to determine the absolute configuration of a chiral molecule. A quarter-wave plate, which is usually made from quartz, can convert linearly polarized light into circularly polarized light. In this stu...

For the simultaneous determination of lactate (LA), 2-hydroxybutyrate (2HB), 3-hydroxybutyrate (3HB) and malate (MA) enantiomers, a new separation technique in a two-dimensional high-performance liquid chromatography (2D-HPLC) system following the fluorescence derivatization with 4-nitro-7-piperazino-2,1,3-benzoxadiazole has been developed. The 2D-...

Bisphosphonates are considered an effective inhibitor of glutamine synthetase and thus can be used for treating tuberculosis (TB). However, its clinical benefit in TB remains unknown. We conducted a population‐based cohort study by using the Taiwan National Health Insurance Research Database and TB databases of the Taiwan Centers for Disease Contro...

Colorectal cancer (CRC) is one of the most common cancers worldwide and its incidence is increasing; therefore, an understanding of its oncogenic mechanisms is critical for improving its treatment and management. Methylglyoxal (MGO) has a highly reactive aldehyde group and has been suggested to play a role in oncogenesis. However, no standardized d...

Enantioselective analysis of lactate (LA) in various fermented food/beverage samples including the Japanese traditional amber rice vinegars was performed using a newly designed three-dimensional high-performance liquid chromatographic (3D-HPLC) system. The enantiomers of LA are reported to be possible biomarkers for some diseases such as diabetic m...

Chronic exposure to aristolochic acid (AA) leads to renal interstitial fibrosis and nephropathy. In this study, we aimed to investigate the renoprotective effects of Panax ginseng extract (GE) and ginsenoside saponin (GS) on AA-induced nephropathy (AAN) in mice. Eighty female C3H/He mice were randomly divided into eight groups, including normal; AA...

Importance Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events. Objective To compare the efficacy and safety of neuraminid...

Background: Previous studies have indicated that statins can reduce the severity of depressive symptoms. However, the optimal choice of statin remains unclear. Therefore, we conducted a network meta-analysis to determine the optimal statin for treating depression. Method: We performed a pairwise and network meta-analysis by searching the PubMed,...

Ethnopharmacological relevance Most Aristolochiaceae plants are prohibited due to aristolochic acid nephropathy (AAN), except Xixin (Asarum spp.). Xixin contains trace amounts of aristolochic acid (AA) and is widely used in Traditional Chinese Medicine. Methylglyoxal and D-lactate are regarded as biomarkers for nephrotoxicity. Aim of the study The...

For the enantiomer discriminated determination of lactate (LA) and 3-hydroxybutyrate (3HB) in various complicated samples, a three-dimensional HPLC (3D-HPLC) system has been designed and developed by investigating the separation of the target analytes from unknown substances observed in the real target matrices. LA and 3HB were pre-column derivatiz...

Background Evidence regarding whether statin use is associated with depression is inconsistent. Therefore, we performed a meta-analysis to investigate this association. Methods We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles written in English and published by March 31, 2020. Th...

The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea...

Background: Most Aristolochiaceae plants are prohibited due to aristolochic acid nephropathy (AAN), except Xixin ( Asarum spp. ). Xixin contains trace amounts of aristolochic acid (AA) and is widely used in Traditional Chinese Medicine. Methylglyoxal and D-lactate are regarded as biomarkers for nephrotoxicity. Thus, this study aimed to evaluate tub...

Nephrotoxicity severely limits the chemotherapeutic efficacy of cisplatin (CDDP). Oxidative stress is associated with CDDP-induced acute kidney injury (AKI). Methylglyoxal (MG) forms advanced glycation end products that elevate oxidative stress. We aimed to explore the role of MG and its metabolite D-lactate and identify the proteins involved in CD...

Nephrotoxic serum (NTS) nephritis occurs in three stages: inflammation, early kidney damage, and severe kidney damage. We quantified the temporal changes in the enantiomers of lactate (LA) and 3-hydroxybutyrate (3HB) in serum and urine during the progression of autoimmune kidney damage in mice with NTS nephritis. Two-dimensional and three-dimension...

Hydrogen-free diamond-like carbon (DLC) films have been deposited on polyimide (PI) substrate at room temperature using the sputtering with a novel nanodiamond target. Also, argon plasma pretreatment procedure for PI substrate was optimized to improve the adhesion and characteristics of the as-prepared DLC film. The deposited DLC film on the PI sub...

Atorvastatin (ATO) inhibited the synthesis of non‐steroidal isoprenoid compounds and possessed pleiotropic effect. However, the detailed mechanism of ATO in preventing gentamicin (GM)‐induced renal injury remained obscure. Although underlying multifaceted mechanisms involving in GM‐induced nephrotoxicity were well known, further work on elucidating...

For the highly chemoselective separations of lactate (LA) and 3-hydroxybutyrate (3HB) enantiomers in mammalian urine, an online three-dimensional HPLC system (3D-HPLC) composed of reversed-phase (KSAARP, 1.0 mm i.d. x 250 mm), mixed-mode (KSAAMX, 1.5 mm i.d. x 250 mm) and enantioselective (Chiralpak AD-H, 2.0 mm i.d. x 250 mm) columns has been deve...

Chronic kidney disease is a worldwide problem, and Pb contamination is a potential risk factor. Since current biomarkers are not sensitive for the diagnosis of Pb-induced nephrotoxicity, novel biomarkers are needed. Metformin has both hypoglycaemic effects and reno-protection ability. However, its mechanism of action is unknown. We aimed to discove...

We have designed photodetectors based on a combination of nanocrystalline diamond (NCD) and bilayer metallic layers in a metal-semiconductor-metal (MSM) structure. The NCD films were deposited on silicon substrates which nucleated by different metallic layers (tungsten, molybdenum) and nanodiamond suspension. We found that the metallic layers not o...

For the enantioselective and simultaneous analysis of lactate and 3-hydroxybutyrate, a validated online two-dimensional high-performance liquid chromatography system using 4-nitro-7-piperazino-2,1,3-benzoxadiazole as a fluorescent derivatization reagent has been developed. For the reversed-phase separation in the first dimension, a Capcell Pak C18...

Aristolochic acid (AA) causes interstitial renal fibrosis, which called aristolochic acid nephropathy (AAN). There is no specific indicator for diagnosing AAN, so this study was to investigate the biomarkers for AAN using a proteomics method. The C3H/He female mice were given ad libitum AA-distilled water (0.5 mg/kg/day) and distilled water for 56...

[This corrects the article DOI: 10.1155/2015/675714.].

Methylglyoxal (MGO) is highly cytotoxic and its levels are elevated in diabetes, nephropathy, and atherosclerosis. However, it has never been studied in liver disease. For this reason, we aimed to assess the levels of MGO and its metabolite D-lactate in an early hepatitis model. Wistar rats were administered CCl4 (0.75 ml/Kg, i.p.) to induce hepati...

Lead (Pb) is an environmental pollutant associated with several diseases, such as nephrotoxicity. Methylglyoxal (MG) is a reactive dicarbonyl compound formed during glycolysis and reported to increase in kidney damage. Metformin is used as a MG scavenger in the clinic. In this study, we investigated the mechanism of Pb-induced renal injury and the...

Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction. Accumulation of MG and its downstream metabolite Nε-(carboxyethyl)lysine (CEL) has been identified in several variations of nephropathy, including diabetic, hypertensive, and gentamicin-induced nephropathies. In this study, we investigated the effects of low-m...

Diabetic nephropathy (DN) has become the major cause of end-stage renal disease. Early detection of disease risk, to enable intervention before advanced renal damage occurs, is an important goal. Microalbuminuria has been used to monitor renal damage in clinical settings for years. In this study, we divided patients with diabetes into different gro...

A two-dimensional chiral high-performance liquid chromatography system was established for simultaneous detection of lactate (LA) and 3-hydroxybutyrate (3HB) enantiomers in human clinical samples. d-LA is increased upon kidney damage but 3HB protected against kidney injury. Therefore, determining the concentrations of d,l-LA and d,l-3HB simultaneou...

Aminoglycosides are widely used to treat infections; however, their applications are limited by nephrotoxicity. With the increase of antibiotic resistance, the use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC) has shown renal protective effects in dialysis patients. However, no study has evaluated LMWC for preventing aminog...

Methylglyoxal (MGO), a byproduct of sugar and lipid metabolic processes, is a major glycating agent. This metabolite reacts with basic residues of proteins and promotes the formation of advanced glycation end products (AGEs). Although MGO and AGEs are widely discussed in the context of diabetes, until recently, MGO was thought to result from insuff...

Aims Aristolochic acid (AA) nephrotoxicity is related to accumulation of methylglyoxal (MGO) and Nε-(carboxymethyl)lysine (CML) in the mouse kidney. We studied the activity of renal semicarbazide-sensitive amine oxidase (SSAO), a key enzyme involved in MGO generation, in AA-treated mice, and investigated nephroprotective effects produced by metform...

The seedings of the substrate with a suspension of nanodiamond particles (NDPs) were widely used as nucleation seeds to enhance the growth of nanostructured diamond films. The formation of agglomerates in the suspension of NDPs, however, may have adverse impact on the initial growth period. Therefore, this paper was aimed at the surface modificatio...

Urinary d-lactate is highly correlated to diabetic nephropathy - a progressive kidney disease in renal glomeruli. In this study, we used a C3H/3e mouse model to investigate the relationship between urinary d-lactate and aristolochic acid nephropathy where the glomerular structure is not affected. The nephropathy was induced using intravenous inject...

Background Kawasaki disease (KD) is an autoimmune disease that is associated with systemic vasculitis and other cardiovascular disorders. Recent studies have shown that the calcium sensor, stromal interaction molecule 1 (STIM1), is a key molecule that modulates functioning of the immune system. In this study, the association of STIM1 polymorphisms...

In this study, we investigated the role of carbonyl stress in gentamicin (GM)-induced renal injury in rats. Carbonyl stress is represented by methylglyoxal (MGO) and its downstream advanced glycation end products, such as Nɛ-(carboxyethyl)lysine (CEL). GM (150mg/kg/day, i.p.) administration for 6 days significantly increased blood urea nitrogen (BU...

The surfaces of implantable biomaterials improving biocompatibility and bioinertness are critical for new application of bioimplantable devices. Diamond-like carbon (DLC) film is a promising biomaterial with use for coating bioimplantable devices because of its good biocompatibility, bioinertness, and mechanical properties. In this study, concurren...

Background: Cantharidin isolated from the blister beetle is used as a traditional Chinese medicine. The anticancer activity of thiadizolyl and some known N-substituted thiazolyl of cantharidin has been reported. We obtained a novel type of cantharidinimides for testing their cytotoxicity in human carcinoma cell lines. The structural modification of...

To find new molecular markers for early diagnosis of diabetic nephropathy, we applied fluorogenic derivatization-liquid chromatography-tandem mass spectrometry to identify the differentially expressed proteins in the kidney of control and streptozotocin-induced diabetic rats. The Sprague-Dawley rats were injected with the sodium citrate buffer or s...

Aristolochic acid, found in the Aristolochia species, causes aristolochic acid nephropathy (AAN) and can develop into renal failure. Methylglyoxal (MGO) is a highly cytotoxic compound generated from the metabolic process of glucose or fatty acids. It binds to proteins and forms N(ε)-(carboxymethyl)lysine (CML), which contributes to aging and diabet...

This study employed a new light source, a light-emitting diode (LED), for fluorescence detection of high-performance liquid chromatography to measure the concentration of trace constituents in biological fluids. Using l-3-hydroxybutyrate ( l-3HB) as a tested trace compound, the function of the new system was compared with that of the current commer...

The aim of this study was to evaluate the reversible factors that could possibly affect outcomes of anti-tuberculosis (anti-TB) treatment. A retrospective observational nested case-control study was performed to evaluate the association of patient and clinical factors with anti-TB therapy outcomes as defined by the World Health Organization (WHO)....

This study investigated the effects of low molecular weight chitosan (LMWC) on the renal functions for aristolochic acid (AA)-induced renal lesions in C3H/He mice. Commercial crab shell chitosan (molecular mass of ∼1100kDa) was hydrolysed using bamboo chitosanase at pH 3.5 and 50°C for 18h. LMWC (with molecular mass of ∼29kDa) was isolated from the...

L-3-Hydroxybutyrate (3HB) and D-3HB are enantiomers that exist in various rat tissues, and the ratio of the 2 compounds is of importance since it may affect glucose utilization in cardiomyocytes. In this study, we determined the concentrations of L-3HB and D-3HB in the tissues of normal and streptozotocin (STZ)-induced diabetic rats of different ag...

For better understanding the complete metabolism and the physiological role of D-lactate, the concentrations of D-lactate in the serum, liver and kidney of normal and diabetic rats were determined by our established column-switching HPLC method with pre-column fluorescence derivatization. Eight-week-old male Sprague-Dawley rats were administered wi...

The concentrations of L-3-hydroxybutyrate (L-3HB) in the serum of aristolochic acid (AA)- treated mice were determined by column-switching high-performance liquid chromatography (HPLC). The samples were derivatized with 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ) and determined fluorimetrically. Total 3-HB derivatives in serum were separated...

Two high-performance liquid chromatograph (HPLC) systems with a Rheodyne Model 7000 switching valve for separation of D- and L-lactate in biological samples has been reported. However, since the switching valve was rotated manually, so that only 10 samples could be determined within one day. For better efficiency, a circuit for rotating the switchi...

A sample of 5 mM naproxen in methanol or ethanol was photoirradiated with a Hanovia 200 W high-pressure quartz Hg lamp. In total, 6 photoproducts derived from each sample were observed from the HPLC chromatograms. Four major photoproducts were separated, and their structures elucidated by EI-MS and various spectroscopic methods. A reaction scheme o...

Purpose: A modified laser capture microdissection (LCM) system is developed to improve resolution to 400 nm, using a laser light (808 nm) transmitted by a near-field tip probe. Materials and methods: Using a 150-nm aperture to heat an ethylene vinyl acetate (EVA) film, melted spots on the average of 400 nm in diameter are generated on the underl...

We determined the concentrations of L-3-hydroxybutyrate (L-3HB) in the serum of normal and aristolochic acid (AA)-treated mice. The samples were derivatized with 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ) and determined fluorimetrically by column-switching high-performance liquid chromatography (HPLC). Total 3-HB derivatives in serum were s...

The activity of lipoprotein lipase (LPL), an enzyme responsible for lipoprotein metabolism, would vary in diseases and metabolic disorders. For determination of LPL activity, a highly sensitive high performance liquid chromatography (HPLC) method using a fluorescent reagent, 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ) was applied to determin...

Arylamine N-acetyltransferase-2 (NAT2) displays extensive genetic polymorphisms that affect the rates of acetylation of drugs and toxic compounds such as amine carcinogens. The association of NAT2 polymorphisms with adult brain tumors has been unclear. To investigate whether the NAT2 genotype is a risk factor of brain tumors, we determined the freq...

Our new constructed LCM system with a near field fiber probe heated the thermoplastic polymer film which placed above the tissue section by focusing laser beam (810 nm), and this method improved the resolution of the dissection capture. In this study, we designed a new cap with a hole, which made the fiber probe exert close melting, and the optimal...

A method for quantitative measurement of the photochemical decomposition of the anti-inflammatory agent, indoprofen (INP) is descriped. An RPLC-based assay that could determine the extent of degradation of INP in a rapid, sensitive, and accurate manner was developed. The method was validated under photoirradiation. Quantitation was monitored with a...

A rapid, accurate and reliable reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of naproxen and its photodegradation products in methanol was developed and validated. An Inertsil 5-ODS-3V column (5 microm, C18, 250 x 4.6 mm i.d.) was used with a mobile phase of acetonitrile-methanol-1% HOAc in H2O (40:20:40...

To survey the knowledge, attitudes, and practices towards safe medication use of first-year college students in Taiwan. One hundred forty-seven departments in 27 universities were sampled by stratified randomization. Three sections of the questionnaire were developed, including 10 true/false questions to measure knowledge, 4 questions for attitude...

In researches of ketone bodies, D-3-hydroxybutyrate (D-3HB) is usually the major one which has been investigated; in contrast, little attention has been paid to L-3-hydroxybutyrate (L-3HB), because of its presence in trace amounts, its dubious metabolism, and a lack of knowledge about its sources. In the present study we determined the distribution...

Laser capture microdissection (LCM) is a microscopy technique by the thermoplastic transfer film of ethylene vinyl acetate (EVA) for targeting and extraction of specific cell from tissue sections. Near-field optical tips were used to focus laser beam for replacing microscope objective of traditional LCM and successfully reduced the capture size to...

We built the Dual Beam Mode of the LDA (Laser Doppler Anemometry) frame, set the photodetector at the same side with light source which collect the scattering light of blood cell. It's proper to reduce LDA optical path and convenient for our designing module. The concentration of chicken blood in this study is about 1% and we measured the relations...

A highly sensitive method for the fluorimetric determination of d-lactate in urine of normal and diabetic rats was developed using column-switching high-performance liquid chromatography (HPLC) with an octadecylsilica (ODS) column connected to a chiral column, an amylose tris(3,5-dimethylphenylcarbamate) coated on silica gel (Chiralpak AD-RH). Duri...

Laser Capture Microdissection (LCM) is a technique that permits rapid and reliable procurement of pure population of cells from tissue sections. We created the LCM system with a near field fiber probe to transmit the laser light (808 nm) to heat the thermoplastic polymer film which was placed above the tissue section. Laser spots in nano-dimension...

A highly sensitive method for the determination of D-lactate in rat urine was developed by using a high-performance liquid chromatography (HPLC) with an octadecylsilica (ODS) connected to a chiral column. At first, (D+L)-lactate in the urine were derivatized with a fluorescent reagent, 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ), and separat...

d-Lactic and l-lactic acids were simultaneously determined by means of a column-switching high-performance liquid chromatography (HPLC) with fluorescence detection. As a fluorescence reagent, 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ) was employed for the fluorescence derivatization of lactic acid. The proposed HPLC system adopted both octy...

L-3-Hydroxybutyrate (L-3HB), the enantiomer of D-3-hydroxybutyrate (D-3HB), has traditionally been regarded the "unnatural" ketone body in mammals, although there is suspicion that it is a more-favorable energy fuel for mammalian tissues than D-3HB. In this study, we demonstrated that L-3HB is an original substance in rat serum by applying fluoresc...

A highly sensitive method for the determination of D-lactic acid and 3-hydroxybutyric acid (3-HB) in rat plasma was developed using high-performance liquid chromatography with octadecylsilica (ODS) connected to a chiral column. At first, (D + L)-lactic acid and 3-HB in the plasma were derivatized with a fluorescent reagent, 4-nitro-7-piperazino-2,1...

Large amounts of D-aspartate (D-Asp) are present in the rat adrenal and pituitary glands. D-Asp is thought to be synthesized in the mammalian body and also accumulates in various tissues following intraperitoneal or intravenous administration. This report examines the origins of D-Asp in the adrenal and pituitary glands. We administered D-Asp to ma...

Free D-amino acid content in some archaea was investigated and D-forms of several amino acids were found in them. In the acidothermophilic archaeon, Thermoplasma acidophilum, the proportion of D-aspartate (D-Asp) to total Asp was as high as 39.7%. Crude extracts of Thermoplasma acidophilum had Asp-specific racemase activity that was pyridoxal 5'-ph...

d-Aspartate (d-Asp) is found in prolactin (PRL)-containing cells of the rat anterior pituitary gland [Lee et al., Brain Res. 838, 193-199, 1999]. In order to determine whether d-Asp is actually produced by the anterior pituitary gland and whether it plays a physiological role in PRL function, a PRL-secreting clonal strain of rat pituitary tumor cel...

Rat pituitary gland and retina were probed with anti-d-aspartate (d-Asp) antibody previously prepared in this laboratory [Lee et al., Biochem. Biophys. Res. Commun., 231 (1997) 505–508]. d-Asp immunoreactivity (IR) was observed only in the posterior lobe of the pituitary gland of 3-day-old rats, whereas the anterior and posterior lobes were also po...

D-Aspartate increases human chorionic gonadotropin-induced testosterone production in purified rat Leydig cells. L-Aspartate, D-,L-glutamate or D-,L-asparagine could not substitute for D-aspartate and this effect was independent of glutamate receptor activation. Testosterone production was enhanced only in cells cultured with D-aspartate for more t...

The rat embryonic brain was probed with anti-d-aspartic acid (d-Asp) antiserum at different stages of development. At gestational day (E) 12, weak immunoreactivity (IR) of d-Asp was apparent at the hindbrain, midbrain and caudal forebrain, whereas it became more intense and extended over the whole brain at E20. However, IR markedly decreased after...

In this communication, we demonstrate that D-aspartate (D-Asp) is synthesized in pheochromocytoma cells (PC12). To our knowledge this is the first report of biosynthesis of D-Asp in mammalian cells. Synthesis of D-Asp was demonstrated by its time-dependent accumulation in the cell culture, and by the fact that this accumulation was proportional to...

Significant amounts of D-aspartate (Asp) are found in mammalian tissues and D-Asp is presumed to play some significant, but as yet undefined physiological role. However, it is not known whether D-Asp is synthesized in mammals. In this study, we addressed this issue in cultured rat pinealocytes, parenchymal cells of the pineal gland, which contain s...

In the current study, localization of D-aspartic acid (D-Asp) in rat testis was studied by immunohistochemical and biochemical techniques. Immunohistochemical staining of this tissue using specific polyclonal antibody to D-Asp revealed D-Asp immunoreactivity (IR) in the cytoplasm of germ cells, especially around the region rich in elongate spermati...

In this communication, we demonstrate that d-aspartate (d-Asp) is synthesized in pheochromocytoma cells (PC12). To our knowledge this is the first report of biosynthesis of d-Asp in mammalian cells. Synthesis of d-Asp was demonstrated by its time-dependent accumulation in the cell culture, and by the fact that this accumulation was proportional to...

Developmental changes in cellular localization of D-aspartic acid (D-Asp) were investigated in rat adrenal gland with polyclonal anti-D-Asp antibody. At 1 and 3 weeks of age, immunoreactivity (IR) toward this amino acid was intense in the cytoplasm of cells in the zona fasciculata (ZF) and zona reticularis (ZR) of the adrenal cortex but was less so...

Specific polyclonal antibody was raised against D-aspartate (D-Asp) which had been conjugated to glutaraldehyde and was purified by affinity chromatography. Immunohistochemical staining of rat pineal gland with the antibody demonstrated the presence of D-Asp in the cytoplasm of pinealocytes, the predominant cell type in this gland. D-Asp immunoreac...

Regional distribution of D-amino acids in the rat brain was studied by highly sensitive HPLC analytical method. The method includes fluorogenic derivatization of each amino acid, isolation of each amino acid by reverse-phase HPLC, followed by enantiomeric separation with a chiral stationary phase. D-Amino acid contents were determined in the cerebr...