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Jinu Han(Jinu Han),Kwangsic Joo(Kwangsic Joo),Ungsoo Samuel Kim(Ungsoo Samuel Kim),Se Joon Woo(Se Joon Woo),Eun Kyoung Lee(Eun Kyoung Lee),Joo Yong Lee(Joo Yong Lee),Tae Kwann Park(Tae Kwann Park),San 대한안과학회 2023 Korean Journal of Ophthalmology Vol.37 No.2
Mutations in the RPE65 gene, associated with Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitispigmentosa, gained growing attention since gene therapy for patients with RPE65-associated retinal dystrophy is available inclinical practice. RPE65 gene accounts for a very small proportion of patients with inherited retinal degeneration, especiallyAsian patients. Because RPE65-associated retinal dystrophy shares common clinical characteristics, such as early-onset severenyctalopia, nystagmus, low vision, and progressive visual field constriction, with retinitis pigmentosa by other geneticmutations, appropriate genetic testing is essential to make a correct diagnosis. Also, fundus abnormalities can be minimal inearly childhood, and the phenotype is highly variable depending on the type of mutations in RPE65-associated retinal dystrophy,which makes a diagnostic difficulty. The aim of this paper is to review the epidemiology of RPE65-associated retinaldystrophy, mutation spectrum, genetic diagnosis, clinical characteristics, and voretigene neparvovec, a gene therapy productfor the treatment of RPE65-related retinal dystrophy.
Inhibitory effect of zinc on hypoxic HIF-1 activation in astrocytes
Kim, Insook,Kim, Chul Hoon,Seo, Gi Ho,Kim, Hyun Soo,Lee, Jinu,Kim, Dong Goo,Ahn, Young Soo Lippincott Williams Wilkins, Inc. 2008 NEUROREPORT - Vol.19 No.10
Hypoxia-inducible factor-1 (HIF-1) regulates the expression of neuroprotective genes such as erythropoietin (EPO). We investigated the mechanism by which zinc, an excitotoxin-like metal, regulates HIF-1 under hypoxic conditions in astrocytes. In hypoxic LN215 cells, HIF-1α stabilized and accumulated in the nucleus, resulting in an increase in its DNA-binding activity to the EPO enhancer. Zinc inhibited hypoxia-induced increases in HIF-1 DNA-binding activity and the HIF-1-dependent mRNA expression of EPO. Zinc did not affect hypoxic stabilization of HIF-1α. Nuclear migration of HIF-1α upon hypoxia was reduced by zinc. Complete blockade of hypoxia-induced assembly of HIF-1α-HIF-1&bgr; complex was observed after treatment of zinc. These findings suggest that zinc hampers hypoxia-stimulated HIF-1 activation in astrocytes by inhibiting nuclear HIF-1α translocation and subsequently disrupting HIF-1 heterodimerization.
Kim, Won-Serk,Kim, Wang-Kyun,Choi, Nahyun,Suh, Wonhee,Lee, Jinu,Kim, Dae-Duk,Kim, Ikyon,Sung, Jong-Hyuk The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3
In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3-thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.
Jinu Kim,Eun Seow Shin,Jeong Eon Kim,Sang Pil Yoon,Young Suk Kim 대한방사선종양학회 2015 Radiation Oncology Journal Vol.33 No.4
Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered
Kim, Jinu,Shin, Eun Seow,Kim, Jeong Eon,Yoon, Sang Pil,Kim, Young Suk The Korean Society for Radiation Oncology 2015 Radiation Oncology Journal Vol.33 No.4
Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered.
( Won-serk Kim ),( Wang-kyun Kim ),( Nahyun Choi ),( Wonhee Suh ),( Jinu Lee ),( Dae-duk Kim ),( Ikyon Kim ),( Jong-hyuk Sung ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3
In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3- thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.
Zinc Inhibits Amyloid Ղ Production from Alzheimer s Amyloid Precursor Protein in SH-SY5Y Cells
Jinu Lee,Chul Hoon Kim,Dong Goo Kim,Young Soo Ahn 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3
Zinc released from excited glutamatergic neurons accelerates amyloidՂ(AՂ)aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer s disease (AD). Zinc can also alter AՂconcentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed AՂproduction, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased AՂ40 and AՂ42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both Ղ- and Ձ-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of AՂ40. These results indicate that inhibition of secretase-mediated APP cleavage accounts-at least in part- for zinc inhibition of AՂ secretion.
In vivo high-throughput profiling of CRISPR–Cpf1 activity
Kim, Hui K,Song, Myungjae,Lee, Jinu,Menon, A Vipin,Jung, Soobin,Kang, Young-Mook,Choi, Jae W,Woo, Euijeon,Koh, Hyun C,Nam, Jin-Wu,Kim, Hyongbum Nature Publishing Group, a division of Macmillan P 2017 Nature methods Vol.14 No.2
<P>CRISPR from Prevotella and Francisella 1 (Cpf1) is an effector endonuclease of the class 2 CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) gene editing system. We developed a method for evaluating Cpf1 activity, based on target sequence composition in mammalian cells, in a high-throughput manner. A library of >11,000 target sequence and guide RNA pairs was delivered into human cells using lentiviral vectors. Subsequent delivery of Cpf1 into this cell library induced insertions and deletions (indels) at the integrated synthetic target sequences, which allowed en masse evaluation of Cpfl activity by using deep sequencing. With this approach, we determined protospacer-adjacent motif sequences of two Cpf1 nucleases, one from Acidaminococcus sp. BV3L6 (hereafter referred to as AsCpf1) and the other from Lachnospiraceae bacterium ND2006 (hereafter referred to as LbCpfl). We also defined target-sequence-dependent activity profiles of AsCpf1, which enabled the development of a web tool that predicts the indel frequencies for given target sequences (http://big.hanyang.ac.kr/cindel). Both the Cpf1 characterization profile and the in vivo high-throughput evaluation method will greatly facilitate Cpf1-based genome editing.</P>