• Imaging Science in Dentistry
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• v.52 no.1
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• pp.33-41
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• 2022

Purpose: This study aimed to evaluate the structural complexity of craniofacial trabecular bone in multiple myeloma by fractal analysis of panoramic and lateral skull radiography, and to compare the fractal dimension values of healthy patients (HPs), pre-treatment patients (PTPs), and patients during bisphosphonate treatment (DTPs). Materials and Methods: Pairs of digital panoramic and lateral skull radiographs of 84 PTPs and 72 DTPs were selected. After application of exclusion criteria, 43 panoramic and 84 lateral skull radiographs of PTPs, 56 panoramic and 72 lateral skull radiographs of DTPs, and 99 panoramic radiographs of age- and sex-matched HPs were selected. The fractal dimension values from panoramic radiographs were compared among HPs, PTPs, and DTPs and between anatomical locations within patient groups using analysis of variance with the Tukey test. Fractal dimension values from lateral skull radiographs were compared between PTPs and DTPs using the Student t-test. Pearson correlation coefficients were used to assess the relationship between the mandible from panoramic radiographs and the skull from lateral skull radiographs. Intra-examiner agreement was assessed using intraclass correlation coefficients (α=0.05). Results: The fractal dimension values were not significantly different among HPs, PTPs, and DTPs on panoramic radiographs or between PTPs and DTPs on lateral skull radiographs (P>0.05). The mandibular body presented the highest fractal dimension values (P≤0.05). The fractal dimension values of the mandible and skull in PTPs and DTPs were not correlated. Conclusion: Fractal analysis was not sensitive for distinguishing craniofacial trabecular bone complexity in multiple myeloma patients using panoramic and lateral skull radiography.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.1
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• pp.30-36
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• 2013

6-pyruvoyltetrahydropterin synthase (PTPS) deficiency is autosomal recessive disorder and the most common type of tetrahydrobiopterin (BH4) deficiency. It is caused by deficiency of PTPS, a cofactor involved in the biosynthesis of BH4 from guanosine triphosphate (GTP). Unlike classical phenylketonuria, which needs restriction of dietary phenylalanine for whole life, BH4 deficiency is treated by tetrahydrobiopterin, levodopa, and 5-hydroxytryptophan replacement. So it is important to make accurate diagnosis and initiate treatment as soon as possible for a better prognosis. There is no retrospective study of Korean patients undergoing long-term treatment for PTPS deficiency. We report 9 Korean patients with PTPS deficiency and their laboratory findings including BH4 loading tests, urine pterin tests, genotypes, dihydropteridine reductase (DHPR) activities and clinical manifestations including medication and developmental delay existence.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1709-1713
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• 2015

Sepiapterin is a precursor for the synthesis of tetrahydrobiopterin (BH4), which is a wellknown cofactor for aromatic amino acid hydroxylation and nitric oxide synthesis in higher mammals. In this study, a recombinant Escherichia coli BL21(DE3) strain harboring cyanobacterial guanosine 5’-triphosphate cyclohydrolase 1 (GCH1) and human 6-pyruvoyltetrahydropterin synthase (PTPS) genes was constructed to produce sepiapterin. The optimum conditions for T₇ promoter–driven expression of GCH1 and PTPS were 30℃ and 0.1 mM isopropyl-β-D-thioglucopyranoside (IPTG). The maximum sepiapterin concentration of 88.1 ± 2.4 mg/l was obtained in a batch cultivation of the recombinant E. coli, corresponding to an 18-fold increase in sepiapterin production compared with the control condition (37℃ and 1 mM IPTG).

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.243.2-244
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• 2002

Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic enzymes. which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Thirty subtypes of PTPs have been identified in human genomes. Among PTPs, PTP1 B has been suggested as a negative regulator of insulin signaling. Overexpression of this enzyme has been known as a cause of obesity and type II diabetes, so it is a target for drug discovery. (omitted)

• BMB Reports
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• v.45 no.12
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• pp.693-699
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• 2012

Together with protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs) serve as hallmarks in cellular signal transduction by controlling the reversible phosphorylation of their substrates. The human genome is estimated to encode more than 100 PTPs, which can be divided into eleven sub-groups according to their structural and functional characteristics. All the crystal structures of catalytic domains of sub-groups have been elucidated, enabling us to understand their precise catalytic mechanism and to compare their structures across all sub-groups. In this review, I describe the structure and mechanism of catalytic domains of PTPs in the structural context.

• BMB Reports
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• v.50 no.6
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• pp.329-334
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• 2017

Protein tyrosine phosphatases (PTPs) play crucial roles in signal transduction and their functional alteration has been detected in many diseases. PTP inhibitors have been developed as therapeutic drugs for diseases that are related to the activity of PTPs. In this study, PTP inhibitor XIX, an inhibitor of CD45 and PTEN, was investigated whether it inhibits other PTPs. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was selectively inhibited by the inhibitor in a competitive manner. Drug affinity responsive target stability (DARTS) analysis showed that the inhibitor induces conformational changes in PTPN2. Phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) at Tyr-705, a crucial site for STAT3 activation and target site of PTPN2, decreased upon exposure to the inhibitor. Our results suggest that PTP inhibitor XIX might be considered as an effective regulator of PTPN2 for treating diseases related to PTPN2.

• Journal of Microbiology and Biotechnology
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• v.27 no.5
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• pp.878-895
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• 2017

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

• Toxicological Research
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• v.34 no.4
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• pp.333-341
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• 2018

Ferulate is a phenolic compound abundant in wheat germ and bran and has been investigated for its beneficial activities. The aim of the present study is to evaluate the efficacy of ferulate against the oxidative stress-induced imbalance of protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs), and serine/threonine protein phosphatase 2A (PP2A), in connection with our previous finding that oxidative stress-induced imbalance of PTKs and PTPs is linked with proinflammatory nuclear factor-kappa B $(NF-{\kappa}B)$ activation. To test the effects of ferulate on this process, we utilized two oxidative stress-induced inflammatory models. First, YPEN-1 cells were pretreated with ferulate for 1 hr prior to the administration of 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). Second, 20-month-old Sprague-Dawley rats were fed ferulate for 10 days. After ferulate treatment, the activities of PTKs, PTPs, and PP2A were measured because these proteins either directly or indirectly promote $NF-{\kappa}B$ activation. Our results revealed that in YPEN-1 cells, ferulate effectively suppressed AAPH-induced increases in reactive oxygen species (ROS) and $NF-{\kappa}B$ activity, as well as AAPH-induced PTK activation. Furthermore, ferulate also inhibited AAPH-induced PTP and PP2A inactivation. In the aged kidney model, ferulate suppressed aging-induced activation of PTKs and ameliorated aging-induced inactivation of PTPs and PP2A. Thus, herein we demonstrated that ferulate could modulate PTK/PTP balance against oxidative stress-induced inactivation of PTPs and PP2A, which is closely linked with $NF-{\kappa}B$ activation. Based on these results, the ability of ferulate to modulate oxidative stress-related inflammatory processes is established, which suggests that this compound could act as a novel therapeutic agent.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6215-6223
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• 2015

Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor-suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.118-126
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• 2015

Background and objectives: A deficiency of BH4 (tetrahydrobiopterin) not only causes the classical phenylketonuric phenotype, but also is the source of neurological signs and symptoms due to impaired syntheses of L-Dopa and serotonin. The treatment of BH4 deficiency usually consists of replacement with BH4 and the neurotransmitters. We performed this study to finding out long-term follow-up clinical symptoms and prognosis of BH4 deficiency. Methods: Clinical and biochemical, genetic analysis were done retrospectively from January 1999 to July 2015 in Soonchunhyang University Hospital. Results: In our study, total 207 patients were confirmed to hyperphenylalaninemia. Among them, 10 patients were BH4 deficiency. 9 patients were 6-pyruvoyl-tetrahydropterin (PTPS) deficiency and one patient was dihydropteridine reductase (DHPR) deficiency. The patients who received delayed treatment, most of our patients suffered from severe psychomotor retardation, hypotonia and seizure. c.259C>T mutation was identified most commonly in PTPS gene analysis. A patient with DHPR deficiency had a mental retardation, dystonia, seizure. His seizure semiology was dialeptic feature. His EEG showed generalized spike wave patterns. All patients had treated with tolerate L-Dopa, BH4 and 5-hydroxytryptophan. Most of the early treated patients have a good tolerance for drugs well. But some patients had neurologic symptoms, despite early detection and treatment. Conclusion: BH4 deficiency patients who had delayed treatment tend to have severe psychomotor problem and neurologic deficits.