(E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) Phenol Ameliorates MPTP-Induced Dopaminergic Neurodegeneration by Inhibiting the STAT3 Pathway.

Neuroinflammation is implicated in dopaminergic neurodegeneration. We have previously demonstrated that (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a selective signal transducer and activator of transcription 3 (STAT3) inhibitor, has anti-inflammatory properties in several inflammatory disease models. We investigated whether MMPP could protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell loss and behavioral impairment.

Loss of parkin reduces lung tumor development by blocking p21 degradation.

Several epidemiological studies have demonstrated the reciprocal relationship between the development of cancer and Parkinson's disease (PD). However, the possible mechanisms underlying this relationship remain unclear. To identify this relationship, we first compared lung tumor growth in parkin knockout (KO) mice and wild-type (WT) mice.

Deficiency of parkin suppresses melanoma tumor development and metastasis through inhibition of MFN2 ubiquitination.

Parkin, a critical gene of Parkinson's disease, is involved in the development of numerous cancers. However, the effect of parkin deficiency on melanoma growth and metastasis has not been reported. We showed that the tumor size and number of surface lung metastases, and expression of tumor growth and metastasis marker proteins were significantly lower in parkin-KO mice than those observed in non-transgenic controls.

Genetic and phenotypic characterization of the novel mouse substrain C57BL/6N Korl with increased body weight.

In inbred mouse lines, there is generally little genetic difference between individuals. This small genetic variability facilitates carrying out research on minute changes of various traits and the gene pool. Also, characterizing the diversity and detecting selective genetic and phenotypic signatures are crucial to understanding the genomic basis of a population and to identify specific patterns of evolutionary change.

Comparison of commonly used ICR stocks and the characterization of Korl:ICR.

Mouse is a commonly used animal in life science studies and is classified as outbred if genetically diverse and inbred if genetically homogeneous. Outbred mouse stocks, are used in toxicology, oncology, infection and pharmacology research. The National Institute of Food and Drug Safety Evaluation (NIFDS; former the Korea National Institute of Health) have bred ICR mice for more than 50 years.

Piperlongumine attenuates experimental autoimmune encephalomyelitis through inhibition of NF-kappaB activity.

Multiple sclerosis (MS) is a chronic, autoimmune and neurodegenerative disease in which demyelination sporadically and repeatedly occurs in the central nervous system (CNS). The activity of nuclear factor kappa B (NF-κB), a family of transcription factors, was increased in the cerebrospinal fluid (CSF) and/or the serum and brain and/or spinal cord of MS patients than in a healthy donors. In our study, we investigated whether piperlongumine (PL), which is known to have inhibitory effect on activity of NF-κB, can alleviate an experimental autoimmune encephalomyelitis (EAE).

Comparison of the response using ICR mice derived from three different sources to ethanol/hydrochloric acid-induced gastric injury.

Animal models for gastric ulcers produced by physical, pharmacological and surgical methods have been widely employed to evaluate therapeutic drugs and investigate the mechanism of action of this disease. ICR mice were selected to produce this model, even though several mice and rats have been widely used in studies of gastric ulcers. To compare the responses of ICR mice obtained from three different sources to gastric ulcer inducers, alterations in gastric injury, histopathological structure, and inflammation were measured in Korl:ICR (Korea NIFDS source), A:ICR (USA source) and B:ICR (Japan source) treated with three concentrations of ethanol (EtOH) (50, 70, and 90%) in 150 mM hydrochloric acid (HCl) solution.

(E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol inhibits growth of colon tumors in mice.

In our previous study, we found that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal showed anti-cancer effect, but it showed lack of stability and drug likeness. We have prepared several (E)-2,4-bis(p-hydroxyphenyl)-2-butenal analogues by Heck reaction. We selected two compounds which showed significant inhibitory effect of colon cancer cell growth.

Exposure-outcome analysis in depressed patients treated with paroxetine using population pharmacokinetics.

Purpose: This study investigated population pharmacokinetics of paroxetine, and then performed an integrated analysis of exposure and clinical outcome using population pharmacokinetic parameter estimates in depressed patients treated with paroxetine.

Patients And Methods: A total of 271 therapeutic drug monitoring (TDM) data were retrospectively collected from 127 psychiatric outpatients. A population nonlinear mixed-effects modeling approach was used to describe serum concentrations of paroxetine.

The influences of CYP2D6 genotypes and drug interactions on the pharmacokinetics of venlafaxine: exploring predictive biomarkers for treatment outcomes.

Rationale: Two biomarkers: concentration ratio of O-desmethylvenlafaxine/venlafaxine and concentration sum of venlafaxine + O-desmethylvenlafaxine were adopted to indicate venlafaxine responses, but neither is validated.

Objectives: To evaluate the ability of two biomarkers in reflecting venlafaxine pharmacokinetic variations, and to further examine their relationship with venlafaxine treatment outcomes.

Methods: Two well-defined influencing factors: CYP2D6 genotypes and drug interactions were enriched into a three-period crossover study to produce venlafaxine pharmacokinetic variations: In each period, healthy CYP2D6 extensive metabolizers (EM group; n = 12) and CYP2D6*10/*10 intermediate metabolizers (IM group; n = 12) were pretreated with clarithromycin (CYP3A4 inhibitor), or nothing (control), or clarithromycin + paroxetine (CYP3A4 + CYP2D6 inhibitors), before administration of a single-dose of 75 mg venlafaxine.

Comprehensive variant screening of the UGT gene family.

Purpose: UGT1A1, UGT2B7, and UGT2B15 are well-known pharmacogenes that belong to the uridine diphosphate glucuronyltransferase gene family. For personalized drug treatment, it is important to study differences in the frequency of core markers across various ethnic groups. Accordingly, we screened single nucleotide polymorphisms (SNPs) of these three genes and analyzed differences in their frequency among five ethnic groups, as well as attempted to predict the function of novel SNPs.

Screening of dihydropyrimidine dehydrogenase genetic variants by direct sequencing in different ethnic groups.

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms.

Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics.

Aim: CYP2C9 enzyme metabolizes numerous clinically important drugs. The aim of this study is to investigate the frequencies of CYP2C9 genotypes and the effects of selected alleles on losartan pharmacokinetics in a large sample of the Korean population.

Methods: The CYP2C9 gene was genotyped in 1796 healthy Korean subjects.

Screening of genetic variations of SLC15A2, SLC22A1, SLC22A2 and SLC22A6 genes.

A growing list of membrane-spanning proteins involved in the transport of a large variety of drugs has been recognized and characterized to include peptide and organic anion/cation transporters. Given such an important role of transporter genes in drug disposition process, the role of single-nucleotide polymorphisms (SNPs) in such transporters as potential determinants of interindividual variability in drug disposition and pharmacological response has been investigated. To define the distribution of transporter gene SNPs across ethnic groups, we screened 450 DNAs in cohorts of 250 Korean, 50 Han Chinese, 50 Japanese, 50 African-American and 50 European-American ancestries for 64 SNPs in four transporter genes encoding proteins of the solute carrier family (SLC15A2, SLC22A1, SLC22A2 and SLC22A6).

Movements of individual BKCa channels in live cell membrane monitored by site-specific labeling using quantum dots.

The movements of BK(Ca) channels were investigated in live cells using quantum dots (QDs). The extracellular N-terminus was metabolically tagged with biotin, labeled with streptavidin-conjugated QDs and then monitored using real-time time-lapse imaging in COS-7 cells and cultured neurons. By tracking hundreds of channels, we were able to determine the characteristics of channel movements quantitatively.

Modulation of the conductance-voltage relationship of the BK(Ca) channel by shortening the cytosolic loop connecting two RCK domains.

Calcium-dependent gating of large-conductance calcium-activated potassium (BK(Ca)) channels is mediated by the intracellular carboxyl terminus, which contains two domains of regulator of K(+) conductance (RCK). In mammalian BK(Ca) channels, the two RCK domains are separated by a protein segment of 101 residues that is poorly conserved in evolution and predicted to have no regular secondary structures. We investigated the functional importance of this loop using a series of deletion mutations.