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| WoS | SCOPUS | Document Type | Document Title | Abstract | Authors | Affiliation | ResearcherID (WoS) | AuthorsID (SCOPUS) | Author Email(s) | Journal Name | JCR Abbreviation | ISSN | eISSN | Volume | Issue | WoS Edition | WoS Category | JCR Year | IF | JCR (%) | FWCI | FWCI Update Date | WoS Citation | SCOPUS Citation | Keywords (WoS) | KeywordsPlus (WoS) | Keywords (SCOPUS) | KeywordsPlus (SCOPUS) | Language | Publication Stage | Publication Year | Publication Date | DOI | JCR Link | DOI Link | WOS Link | SCOPUS Link |
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| ○ | ○ | Article | Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation | Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and glutaminolysis are increased in rapidly proliferating VSMCs to support their increased energy requirements and biomass production. Thus, it is essential to develop new pharmacological tools that regulate metabolic reprogramming in VSMCs for treatment of atherosclerosis. The effects of 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist, have been broadly investigated in highly proliferative cells; however, it is unclear whether DON inhibits proliferation of VSMCs and neointima formation. Here, we investigated the effects of DON on neointima formation in vivo as well as proliferation and migration of VSMCs in vitro. DON simultaneously inhibited FBS- or PDGF-stimulated glycolysis and glutaminolysis as well as mammalian target of rapamycin complex I activity in growth factor-stimulated VSMCs, and thereby suppressed their proliferation and migration. Furthermore, a DON-derived prodrug, named JHU-083, significantly attenuated carotid artery ligation-induced neointima formation in mice. Our results suggest that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis. | Park, Hyeon Young; Kim, Mi-Jin; Lee, Seunghyeong; Jin, Jonghwa; Lee, Sungwoo; Kim, Jung-Guk; Choi, Yeon-Kyung; Park, Keun-Gyu | Kyungpook Natl Univ, Grad Sch, Dept Biomed Sci, Daegu 41566, South Korea; Kyungpook Natl Univ, Sch Med, BK21 FOUR KNU Convergence Educ Program Biomed Sci, Daegu 41566, South Korea; Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Internal Med, Daegu 41944, South Korea; Kyungpook Natl Univ, Res Inst Aging & Metab, Daegu 41566, South Korea; Daegu Gyeongbuk Med Innovat Fdn, New Drug Dev Ctr, Daegu 41061, South Korea | 57223237652; 56984392800; 57204501802; 57223246243; 57189250997; 16506485900; 35335932600; 57202558343 | coolphyp@gmail.com;kij200@nate.com;ngell92@gmail.com;becauseofu77@gmail.com;swlee@dgmif.re.kr;jugkim@knu.ac.kr;ykchoi@knu.ac.kr;kpark@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 11 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.88 | 2025-07-30 | 16 | 17 | glutamine antagonist; vascular smooth muscle cells; glycolysis; oxidative phosphorylation; mTORC1 | SMOOTH-MUSCLE-CELL; 6-DIAZO-5-OXO-L-NORLEUCINE DON; MAMMALIAN TARGET; METABOLISM; MTOR; GROWTH; APOPTOSIS; DELIVERY; PRODRUGS | Glutamine antagonist; Glycolysis; MTORC1; Oxidative phosphorylation; Vascular smooth muscle cells | Animals; Antimetabolites, Antineoplastic; Cell Cycle; Cell Movement; Cell Proliferation; Cells, Cultured; Diazooxonorleucine; Glutamine; Glycolysis; Immunohistochemistry; Male; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Inbred C57BL; Mitochondria; Muscle, Smooth, Vascular; Neointima; Oxidative Phosphorylation; Platelet-Derived Growth Factor; Rats; Rats, Sprague-Dawley; Serum Albumin, Bovine; 6 diazo 5 oxonorleucine; jhu 083; mammalian target of rapamycin complex 1; platelet derived growth factor; prodrug; unclassified drug; 6 diazo 5 oxonorleucine; antineoplastic antimetabolite; bovine serum albumin; glutamine; mammalian target of rapamycin complex 1; platelet derived growth factor; animal cell; animal experiment; animal model; antiproliferative activity; Article; carotid artery ligation; controlled study; drug bioavailability; drug effect; fetal bovine serum; glycolysis; in vivo study; male; migration inhibition; mitochondrial respiration; mouse; neointima; nonhuman; oxidative phosphorylation; treatment duration; upregulation; vascular smooth muscle cell; animal; C57BL mouse; cell culture; cell cycle; cell motion; cell proliferation; glycolysis; immunohistochemistry; metabolism; mitochondrion; neointima; oxidative phosphorylation; rat; Sprague Dawley rat; vascular smooth muscle | English | 2021 | 2021-06 | 10.3390/ijms22115602 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | ○ | Article | Isolation and Characterization of Compounds from Glycyrrhiza uralensis as Therapeutic Agents for the Muscle Disorders | Skeletal muscle is the most abundant tissue and constitutes about 40% of total body mass. Herein, we report that crude water extract (CWE) of G. uralensis enhanced myoblast proliferation and differentiation. Pretreatment of mice with the CWE of G. uralensis prior to cardiotoxin-induced muscle injury was found to enhance muscle regeneration by inducing myogenic gene expression and downregulating myostatin expression. Furthermore, this extract reduced nitrotyrosine protein levels and atrophy-related gene expression. Of the five different fractions of the CWE of G. uralensis obtained, the ethyl acetate (EtOAc) fraction more significantly enhanced myoblast proliferation and differentiation than the other fractions. Ten bioactive compounds were isolated from the EtOAc fraction and characterized by GC-MS and NMR. Of these compounds (4-hydroxybenzoic acid, liquiritigenin, (R)-(-)-vestitol, isoliquiritigenin, medicarpin, tetrahydroxymethoxychalcone, licochalcone B, liquiritin, liquiritinapioside, and ononin), liquiritigenin, tetrahydroxymethoxychalcone, and licochalcone B were found to enhance myoblast proliferation and differentiation, and myofiber diameters in injured muscles were wider with the liquiritigenin than the non-treated one. Computational analysis showed these compounds are non-toxic and possess good drug-likeness properties. These findings suggest that G. uralensis-extracted components might be useful therapeutic agents for the management of muscle-associated diseases. | Lee, Eun Ju; Shaikh, Sibhghatulla; Ahmad, Khurshid; Ahmad, Syed Sayeed; Lim, Jeong Ho; Park, Soyoung; Yang, Hye Jin; Cho, Won-Kyung; Park, Sang-Joon; Lee, Yong-Ho; Park, So-Young; Ma, Jin-Yeul; Choi, Inho | Yeungnam Univ, Dept Med Biotechnol, Gyongsan 38541, South Korea; Yeungnam Univ, Res Inst Cell Culture, Gyongsan 38541, South Korea; Yeungnam Univ, Dept Physiol, Coll Med, Daegu 42415, South Korea; Korea Inst Oriental Med KIOM, Korean Med KM Applicat Ctr, Daegu 701300, South Korea; Kyungpook Natl Univ, Coll Vet Med, Daegu 41566, South Korea; Daegu Catholic Univ, Dept Biomed Sci, Gyongsan 38430, South Korea | ; Shaikh, Sibhghatulla/N-8476-2019; Ahmad, Khurshid/M-4676-2014; Park, So-Young/AAC-5528-2022; Ahmad, Syed Sayeed Ahmad/AAH-5177-2020 | 57223272919; 59832956800; 56258941900; 56278691300; 57192958382; 57205434058; 36697427900; 7401774603; 7501825941; 57205255582; 58764721300; 56406839400 | gorapadoc0315@hanmail.net;sibhghat.88@gmail.com;ahmadkhursheed2008@gmail.com;sayeedahmad4@gmail.com;lim2249@naver.com;soyoung614@hanmail.net;hjyang@kiom.re.kr;wkcho@kiom.re.kr;psj26@knu.ac.kr;ylee325@cu.ac.kr;sypark@med.yu.ac.kr;jyma@kiom.re.kr;inhochoi@ynu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 2 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 1.99 | 2025-07-30 | 39 | 32 | skeletal muscle; bioactive compounds; muscle regeneration; Glycyrrhiza uralensis | Bioactive compounds; Glycyrrhiza uralensis; Muscle regeneration; Skeletal muscle | Animals; Cell Differentiation; Cell Line; Cell Proliferation; Chalcones; Flavanones; Glycyrrhiza uralensis; Male; Mice; Mice, Inbred C57BL; Muscular Atrophy; Myoblasts; Myostatin; Plant Extracts; Tyrosine; 3 nitrotyrosine; 4 hydroxybenzoic acid; acetic acid ethyl ester; cardiotoxin; Glycyrrhiza uralensis extract; isoliquiritigenin; licochalcone B; liquiritigenin; liquiritin; liquiritinapioside; medicarpin; myostatin; ononin; tetrahydroxymethoxychalcone; unclassified drug; vestitol; 3-nitrotyrosine; chalcone derivative; flavanone derivative; liquiritigenin; myostatin; plant extract; tyrosine; animal cell; animal experiment; animal model; animal tissue; Article; cell differentiation; cell proliferation; controlled study; down regulation; drug isolation; gene expression; Glycyrrhiza uralensis; male; mass fragmentography; mouse; muscle atrophy; muscle injury; muscle regeneration; myoblast; nonhuman; skeletal muscle; animal; C57BL mouse; cell differentiation; cell line; cell proliferation; chemistry; cytology; drug effect; genetics; metabolism; muscle atrophy; myoblast | English | 2021 | 2021-01 | 10.3390/ijms22020876 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | ○ | Article | Isoleucilactucin Ameliorates Coal Fly Ash-Induced Inflammation through the NF-κB and MAPK Pathways in MH-S Cells | We investigated whether isoleucilactucin, an active constituent of Ixeridium dentatum, reduces inflammation caused by coal fly ash (CFA) in alveolar macrophages (MH-S). The anti-inflammatory effects of isoleucilactucin were assessed by measuring the concentration of nitric oxide (NO) and the expression of pro-inflammatory mediators in MH-S cells exposed to CFA-induced inflammation. We found that isoleucilactucin reduced CFA-induced NO generation dose-dependently in MH-S cells. Moreover, isoleucilactucin suppressed CFA-activated proinflammatory mediators, including cyclooxygenase-2 (COX2) and inducible NO synthase (iNOS), and the proinflammatory cytokines such as interleukin-(IL)-1 beta, IL-6, and tumor necrosis factor (TNF-alpha). The inhibiting properties of isoleucilactucin on the nuclear translocation of phosphorylated nuclear factor-kappa B (p-NF-kappa B) were observed. The effects of isoleucilactucin on the NF-kappa B and mitogen-activated protein kinase (MAPK) pathways were also measured in CFA-stimulated MH-S cells. These results indicate that isoleucilactucin suppressed CFA-stimulated inflammation in MH-S cells by inhibiting the NF-kappa B and MAPK pathways, which suggest it might exert anti-inflammatory properties in the lung. | Ullah, H. M. Arif; Kwon, Tae-Hyung; Park, SeonJu; Kim, Sung Dae; Rhee, Man Hee | Kyungpook Natl Univ, Coll Vet Med, Dept Vet Med, Daegu 41566, South Korea; Chuncheon Bioind Fdn CBF, Dept Res & Dev, Chunchon 24232, South Korea; Korea Basic Sci Inst KBSI, Chuncheon Ctr, Chunchon 24341, South Korea | Ullah, H/AAE-5513-2021; Rhee, Man/O-5705-2016; Park, SeonJu/AAF-8698-2019 | 57198885380; 55419730800; 55363021300; 55156746000; 57211035357 | arif55dml@knu.ac.kr;team0218@cbf.or.kr;sjp19@kbsi.re.kr;kim79sd@knu.ac.kr;rheemh@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 17 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.52 | 2025-07-30 | 8 | 8 | lung macrophages; isoleucilactucin; anti-inflammatory properties; NF-kappa B pathway; AMPK pathway | NITRIC-OXIDE SYNTHASE; TRANSCRIPTION FACTOR; PARTICULATE MATTER; SESQUITERPENE LACTONE; AIR-POLLUTION; EXPRESSION; COX-2; ALPHA; INOS; INTERVENTION | AMPK pathway; Anti-inflammatory properties; Isoleucilactucin; Lung macrophages; NF-κB pathway | Animals; Anti-Inflammatory Agents; Asteraceae; Cell Line; Coal Ash; Inflammation; Macrophages, Alveolar; MAP Kinase Signaling System; Mice; NF-kappa B; Phytochemicals; antiinflammatory agent; cyclooxygenase 2; cytokine; glyceraldehyde 3 phosphate dehydrogenase; immunoglobulin enhancer binding protein; inducible nitric oxide synthase; interleukin 1beta; interleukin 6; isoleucilactucin; Janus kinase; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase p38; nitric oxide; nitric oxide synthase; plant medicinal product; stress activated protein kinase; tumor necrosis factor; unclassified drug; antiinflammatory agent; immunoglobulin enhancer binding protein; phytochemical; animal cell; animal experiment; animal model; antiinflammatory activity; Article; cell viability; controlled study; cytokine production; enzyme phosphorylation; fly ash; Freund adjuvant-induced inflammation; immunofluorescence; Ixeridium dentatum; lung alveolus macrophage; MAPK signaling; MH-S cell line; mouse; mRNA expression level; NF kB signaling; nonhuman; real time polymerase chain reaction; reverse transcription polymerase chain reaction; signal transduction; Western blotting; animal; Asteraceae; cell line; chemistry; drug effect; fly ash; inflammation; MAPK signaling; metabolism; pathology; toxicity | English | 2021 | 2021-09 | 10.3390/ijms22179506 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Metabolite Profiling of Manilkara zapota L. Leaves by High-Resolution Mass Spectrometry Coupled with ESI and APCI and In Vitro Antioxidant Activity, α-Glucosidase, and Elastase Inhibition Assays | High-resolution mass spectrometry equipped with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources was used to enhance the characterization of phytochemicals of ethanol extracts of Manilkara zapota L. leaves (ZLE). Sugar compounds, dicarboxylic acids, compounds of phenolic acids and flavonoids groups, and other phytochemicals were detected from the leaves. Antioxidant activity and inhibition potentiality of ZLE against alpha-glucosidase enzyme, and elastase enzyme activities were evaluated in in vitro analysis. ZLE significantly inhibited activities of alpha-glucosidase enzyme at a lower concentration (IC50 2.51 +/- 0.15 mu g/mL). Glucose uptake in C2C12 cells was significantly enhanced by 42.13 +/- 0.15% following the treatment with ZLE at 30 mu g/mL. It also exhibited potential antioxidant activities and elastase enzyme inhibition activity (IC50 27.51 +/- 1.70 mu g/mL). Atmospheric pressure chemical ionization mass spectrometry (APCI-MS) detected more m/z peaks than electrospray ionization mass spectrometry (ESI-MS), and both ionization techniques illustrated the biological activities of the detected compounds more thoroughly compared to single-mode analysis. Our findings suggest that APCI along with ESI is a potential ionization technique for metabolite profiling, and ZLE has the potential in managing diabetes by inhibiting alpha-glucosidase activity and enhancing glucose uptake. | Islam, Syful; Alam, Md Badrul; Ann, Hyeon-Jin; Park, Ji-Hyun; Lee, Sang-Han; Kim, Sunghwan | Kyungpook Natl Univ, Dept Chem, Daegu 41566, South Korea; Munshiganj Dist Off, Dept Environm, Munshiganj 1500, Bangladesh; Kyungpook Natl Univ, Dept Food Sci & Biotechnol, Daegu 41566, South Korea; Kyungpook Natl Univ, Inner Beauty Antiaging Ctr, Food & Bioind Res Inst, Daegu 41566, South Korea; Knu BnC, Daegu 41566, South Korea; Kyungpook Natl Univ, Mass Spectrometry Converging Res Ctr, Daegu 41566, South Korea; Kyungpook Natl Univ, Green Nano Mat Res Ctr, Daegu 41566, South Korea | Alam, Md Badrul/AFL-7668-2022; Islam, Syful/AAZ-5084-2021; Kim, Sunghwan/HKN-9812-2023; Lee, Seung Eun/ABG-1607-2021 | 57213340400; 56706777100; 57221288131; 57209657621; 57221453703; 57203772967 | msi412@yahoo.com;mbalam@knu.ac.kr;jiny345@knu.ac.kr;wlgus6744@knu.ac.kr;sang@knu.ac.kr;sunghwank@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 1 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 1.4 | 2025-07-30 | 23 | 20 | Manilkara zapota L.; electrospray ionization (ESI); atmospheric pressure chemical ionization (APCI); antioxidant; alpha-glucosidase | PHENOLIC-COMPOUNDS; ELECTROSPRAY-IONIZATION; IDENTIFICATION; MS/MS; CONSTITUENTS; POLYPHENOLS; CAPACITY; NMR | Antioxidant; Atmospheric pressure chemical ionization (APCI); Electrospray ionization (ESI); Manilkara zapota L.; α-glucosidase | alpha-Glucosidases; Animals; Antioxidants; Atmospheric Pressure; Cell Line, Tumor; Flavonoids; Glucose; Glycoside Hydrolase Inhibitors; Inhibitory Concentration 50; Manilkara; Mice; Pancreatic Elastase; Phytochemicals; Plant Leaves; Serine Proteinase Inhibitors; Spectrometry, Mass, Electrospray Ionization; 3 glucogallic acid; 3 hydroxycoumarin; 3 o galloylquinic acid; 3 oxoadipic acid; 3 para coumaroylquinic acid; acarbose; adipic acid; afzelechin; alcohol; alpha glucosidase; alpha glucosidase inhibitor; ampelopsin; antioxidant; ascorbic acid; caffeic acid; chlorogenic acid; dicarboxylic acid derivative; elastase; elastase inhibitor; epicatechin; epigallocatechin; epigallocatechin gallate; esculetin; ferulic acid; flavonoid; gallic acid; glucose; guaiacol; hydroquinone glucuronide; laricitrin 3 o rhamnoside; leucodelphinidin; malic acid; Manilkara zapota extract; myricetin; myricetin 3 o rhamnoside; norathyriol; phenol derivative; plant extract; prodelphinidin B; protocatechuic acid; pyroglutamic acid; quinic acid; rhamnose; rosiglitazone; salicylaldehyde; salicylic acid; shikimic acid; succinic acid; sucrose; syringic acid; threonic acid; unclassified drug; vanillic acid; vanillin; alpha glucosidase; antioxidant; glucose; glycosidase inhibitor; pancreatic elastase; phytochemical; serine proteinase inhibitor; ABTS radical scavenging assay; animal cell; antioxidant activity; Article; atmospheric pressure chemical ionization mass spectrometry; biological activity; C2C12 cell line; concentration response; controlled study; cupric reducing antioxidant capacity assay; data analysis software; DPPH radical scavenging assay; drug efficacy; drug mechanism; electrospray mass spectrometry; enzyme activity; enzyme inhibition; ethnopharmacology; ferric reducing antioxidant power assay; free radical scavenging assay; glucose transport; IC50; in vitro study; intermethod comparison; metabolic fingerprinting; mouse; negative ion electrospray; nonhuman; phytochemistry; plant leaf; sapodilla; tandem mass spectrometry; animal; atmospheric pressure; electrospray mass spectrometry; Manilkara; metabolism; procedures; tumor cell line | English | 2021 | 2021-01 | 10.3390/ijms22010132 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Review | Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer's Disease | Alzheimer's disease (AD) is the most frequent cause of age-related neurodegeneration and cognitive impairment, and there are currently no broadly effective therapies. The underlying pathogenesis is complex, but a growing body of evidence implicates mitochondrial dysfunction as a common pathomechanism involved in many of the hallmark features of the AD brain, such as formation of amyloid-beta (A beta) aggregates (amyloid plaques), neurofibrillary tangles, cholinergic system dysfunction, impaired synaptic transmission and plasticity, oxidative stress, and neuroinflammation, that lead to neurodegeneration and cognitive dysfunction. Indeed, mitochondrial dysfunction concomitant with progressive accumulation of mitochondrial A beta is an early event in AD pathogenesis. Healthy mitochondria are critical for providing sufficient energy to maintain endogenous neuroprotective and reparative mechanisms, while disturbances in mitochondrial function, motility, fission, and fusion lead to neuronal malfunction and degeneration associated with excess free radical production and reduced intracellular calcium buffering. In addition, mitochondrial dysfunction can contribute to amyloid-beta precursor protein (APP) expression and misprocessing to produce pathogenic fragments (e.g., A beta 1-40). Given this background, we present an overview of the importance of mitochondria for maintenance of neuronal function and how mitochondrial dysfunction acts as a driver of cognitive impairment in AD. Additionally, we provide a brief summary of possible treatments targeting mitochondrial dysfunction as therapeutic approaches for AD. | Sharma, Chanchal; Kim, Sehwan; Nam, Youngpyo; Jung, Un Ju; Kim, Sang Ryong | Kyungpook Natl Univ, Sch Life Sci, Daegu 41566, South Korea; Kyungpook Natl Univ, BK21 KNU Creat BioRes Grp 4, Daegu 41566, South Korea; Kyungpook Natl Univ, Brain Sci & Engn Inst, Daegu 41404, South Korea; Pukyong Natl Univ, Dept Food Sci & Nutr, Busan 48513, South Korea | 57193577728; 57193232250; 55143100300; 7007119425; 56486163800 | chanchalmrt@gmail.com;arputa@naver.com;blackpyo2@naver.com;jungunju@pknu.ac.kr;srk75@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 9 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 3.44 | 2025-07-30 | 151 | 155 | Alzheimer’ s disease; mitochondria; free radical; mitophagy; calcium buffering | AMYLOID-BETA TOXICITY; OXIDATIVE STRESS; QUALITY-CONTROL; THERAPEUTIC-TARGET; LIPID-PEROXIDATION; DNA MUTATIONS; MOUSE MODEL; A-BETA; PROTECTS; NEUROPATHOLOGY | Alzheimer’s disease; Calcium buffering; Free radical; Mitochondria; Mitophagy | Alzheimer Disease; Brain; Cognitive Dysfunction; Humans; Mitochondria; Neurons; Oxidative Stress; Plaque, Amyloid; amyloid precursor protein; free radical; mitochondrial DNA; aging; Alzheimer disease; axon; bioenergy; calcium signaling; cognition; cognitive defect; dendrite; disorders of mitochondrial functions; endoplasmic reticulum; energy metabolism; human; lipid homeostasis; memory disorder; metabolic syndrome X; mitochondrial dynamics; mitochondrion; nerve cell; nerve ending; nonhuman; quality control; Review; synapse; Alzheimer disease; amyloid plaque; brain; cognitive defect; genetics; metabolism; oxidative stress; pathology | English | 2021 | 2021-05 | 10.3390/ijms22094850 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | ○ | Article | New Inhibitors of Laccase and Tyrosinase by Examination of Cross-Inhibition between Copper-Containing Enzymes | Coppers play crucial roles in the maintenance homeostasis in living species. Approximately 20 enzyme families of eukaryotes and prokaryotes are known to utilize copper atoms for catalytic activities. However, small-molecule inhibitors directly targeting catalytic centers are rare, except for those that act against tyrosinase and dopamine-beta-hydroxylase (DBH). This study tested whether known tyrosinase inhibitors can inhibit the copper-containing enzymes, ceruloplasmin, DBH, and laccase. While most small molecules minimally reduced the activities of ceruloplasmin and DBH, aside from known inhibitors, 5 of 28 tested molecules significantly inhibited the function of laccase, with the K-i values in the range of 15 to 48 mu M. Enzyme inhibitory kinetics classified the molecules as competitive inhibitors, whereas differential scanning fluorimetry and fluorescence quenching supported direct bindings. To the best of our knowledge, this is the first report on organic small-molecule inhibitors for laccase. Comparison of tyrosinase and DBH inhibitors using cheminformatics predicted that the presence of thione moiety would suffice to inhibit tyrosinase. Enzyme assays confirmed this prediction, leading to the discovery of two new dual tyrosinase and DBH inhibitors. | Chaudhary, Dinesh; Chong, Fangchen; Neupane, Trilok; Choi, Joonhyeok; Jee, Jun-Goo | Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, 80 Daehak Ro, Daegu 41566, South Korea | 57195347438; 57375369700; 57376280100; 56849594100; 7004327823 | pudinesh26@gmail.com;chongfangchen@foxmail.com;ozitrilok99@gmail.com;crowz124@naver.com;jjee@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1661-6596 | 1422-0067 | 22 | 24 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.37 | 2025-07-30 | 8 | 7 | cheminformatics; ceruloplasmin; dopamine-beta-hydroxylase; laccase; tyrosinase | CRYSTAL-STRUCTURE; MUSHROOM TYROSINASE; POTENT; CERULOPLASMIN; DISCOVERY; INSIGHTS; OXIDASE; DRUGS | Ceruloplasmin; Cheminformatics; Dopamine‐β‐hydroxylase; Laccase; Tyrosinase | Agaricales; Biocatalysis; Catalytic Domain; Ceruloplasmin; Cheminformatics; Copper; Dopamine beta-Hydroxylase; Enzyme Inhibitors; Fungal Proteins; Fungi; Humans; Laccase; Models, Molecular; Protein Conformation; Small Molecule Libraries; captopril; ceruloplasmin; copper; dimercaprol; dopamine beta monooxygenase; enzyme inhibitor; kojic acid; laccase; mercaptopurine; monophenol monooxygenase; propylthiouracil; sodium azide; succimer; tetrathiomolybdate ammonium; tioguanine; tropolone; ceruloplasmin; copper; dopamine beta monooxygenase; enzyme inhibitor; fungal protein; laccase; Article; cheminformatics; comparative study; competitive inhibition; concentration response; controlled study; enzyme active site; enzyme activity; enzyme assay; enzyme inhibition; enzyme kinetics; fluorescence; fluorometry; molecular size; nonhuman; Agaricales; biocatalysis; chemistry; enzymology; fungus; human; metabolism; molecular library; molecular model; pharmacology; protein conformation | English | 2021 | 2021-12 | 10.3390/ijms222413661 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B | Human hepatocellular carcinoma (HCC) is the most common and even worse at prognosis. The patients with HCC which accompanied by other diseases, such as cirrhosis, can be limited in various treatments, such as chemotherapy, not HCC patients without other diseases. NLRP3 inflammasome plays an important role in the innate immune response, but emerging evidence has indicated that the NLRP3 inflammasome is implicated in all stages of cancer development. Various cells express NLRP3 protein through the autocrine or paracrine signaling in their environment, but NK cells do not. The expanding evidence shows that patients who suffer from liver cancers have a low frequency of natural killer (NK) cells, and the function of these cells is also impaired. Thus, we examined how the expression of NLRP3 in HCC cells affects cancer surveillance by NK cells in a state of a co-culture of both cells. When the expression of NLRP3 in HCC cells was ablated, MICA/B on the surface of HCC cells was upregulated through the lowered expression of matrix metalloproteinase. The expression of MICA on the surface of HCC cells interacted with the NKG2D receptor on NK-92 cells, which led to NK cytotoxicity. Furthermore, in a xenograft mice model, NLRP3 KO HCC cells delayed tumor development and metastasis as well as increased the sensitivity to NK cell cytotoxicity. Taken together, NLRP3 KO in HCC could enhance NK immunosurveillance through an interaction of NKG2D-MICA. | Lee, Hwan Hee; Kim, Dongoh; Jung, Joohee; Kang, Hyojeung; Cho, Hyosun | Duksung Womens Univ, Dept Pharm, Seoul 01369, South Korea; Duksung Womens Univ, Duksung Innovat Drug Ctr, Seoul 01369, South Korea; Kyungpook Natl Univ, Coll Pharm, Vessel Organ Interact Res Ctr, Canc Res Inst,VOICE MRC, Daegu 41566, South Korea | ; Jung, Joohee/KHD-8426-2024 | 56271051000; 36448440900; 8858539100; 8979751700; 55572361200 | oeo3oeo@gmail.com;kdo9710@naver.com;joohee@duksung.ac.kr;hkang72@knu.ac.kr;hyosun1102@duksung.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1661-6596 | 1422-0067 | 22 | 17 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 1.7 | 2025-07-30 | 26 | 26 | natural killer (NK) cell; hepatocellular carcinoma (HCC); NLRP3; MICA; B; xenograft model | MATRIX METALLOPROTEINASES; CUTTING EDGE; INFLAMMASOME; CELLS; PROGRESSION; MECHANISMS; LIVER | Hepatocellular carcinoma (HCC); MICA/B; Natural killer (NK) cell; NLRP3; Xenograft model | Animals; Apoptosis; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Proliferation; CRISPR-Cas Systems; Cytotoxicity, Immunologic; Disease Models, Animal; Female; Gene Expression Regulation, Neoplastic; Histocompatibility Antigens Class I; Humans; Killer Cells, Natural; Liver Neoplasms; Mice; Mice, Inbred NOD; Mice, SCID; Monitoring, Immunologic; NLR Family, Pyrin Domain-Containing 3 Protein; Tumor Cells, Cultured; Xenograft Model Antitumor Assays; cryopyrin; matrix metalloproteinase; mica protein; natural killer cell receptor NKG2D; oncoprotein; unclassified drug; cryopyrin; HLA antigen class 1; MHC class I-related chain A; MICB antigen; NLRP3 protein, human; tumor marker; animal experiment; animal model; animal tissue; Article; cancer inhibition; cell surface; coculture; controlled study; CRISPR-CAS9 system; epithelial mesenchymal transition; female; gene deletion; human; human cell; immunosurveillance; liver cell carcinoma; metastasis inhibition; mouse; natural killer cell; natural killer cell mediated cytotoxicity; NK-92 cell line; nonhuman; protein expression; tumor xenograft; upregulation; animal; apoptosis; cell proliferation; CRISPR Cas system; cytotoxicity; disease model; drug screening; gene expression regulation; genetics; immunological monitoring; immunology; liver cell carcinoma; liver tumor; metabolism; natural killer cell; nonobese diabetic mouse; pathology; procedures; SCID mouse; tumor cell culture | English | 2021 | 2021-09 | 10.3390/ijms22179285 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |
| ○ | ○ | Article | Novel Pyridine Bioisostere of Cabozantinib as a Potent c-Met Kinase Inhibitor: Synthesis and Anti-Tumor Activity against Hepatocellular Carcinoma | Two novel bioisosteres of cabozantinib, 3 and 4, were designed and synthesized. The benzene ring in the center of the cabozantinib structure was replaced by trimethylpyridine (3) and pyridine (4), respectively. Surprisingly, the two compounds showed extremely contrasting mesenchymal-epithelial transition factor (c-Met) inhibitory activities at 1 mu M concentration (4% inhibition of 3 vs. 94% inhibition of 4). The IC50 value of compound 4 was 4.9 nM, similar to that of cabozantinib (5.4 nM). A ligand-based docking study suggested that 4 includes the preferred conformation for the binding to c-Met in the conformational ensemble, but 3 does not. The anti-proliferative activity of compound 4 against hepatocellular carcinoma (Hep3B and Huh7) and non-small-cell lung cancer (A549 and H1299) cell lines was better than that of cabozantinib, whereas 3 did not show a significant anti-proliferative activity. Moreover, the tumor selectivity of compound 4 toward hepatocellular carcinoma cell lines was higher than that of cabozantinib. In the xenograft chick tumor model, compound 4 inhibited Hep3B tumor growth to a much greater extent than cabozantinib. The present study suggests that compound 4 may be a good therapeutic candidate against hepatocellular carcinoma. | Karmacharya, Ujjwala; Guragain, Diwakar; Chaudhary, Prakash; Jee, Jun-Goo; Kim, Jung-Ae; Jeong, Byeong-Seon | Yeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea; Kyungpook Natl Univ, Coll Pharm, Daegu 41566, South Korea | ; Guragain, Diwakar/AGN-8960-2022; Jeong, Byeong-Seon/C-9061-2019 | 57191042671; 57216684580; 57203412971; 7004327823; 7601363878; 34975054400 | Karmacharya@ynu.ac.kr;diwakarguragain@ynu.ac.kr;prakash@ynu.ac.kr;jjee@knu.ac.kr;jakim@yu.ac.kr;jeongb@ynu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 18 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.81 | 2025-07-30 | 12 | 12 | mesenchymal-epithelial transition factor (c-Met); bioisosteric replacement; anti-proliferative activity; tumor selectivity; hepatocellular carcinoma; anti-tumor efficacy | HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; EXPRESSION; ONCOGENE; DESIGN; IDENTIFICATION; GENERATION; MECHANISM; DISCOVERY; DOCKING | Anti-proliferative activity; Anti-tumor efficacy; Bioisosteric replacement; Hepatocellular carcinoma; Mesenchymal–epithelial transition factor (c-Met); Tumor selectivity | Anilides; Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Liver Neoplasms; Mice; Molecular Structure; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Pyridines; Xenograft Model Antitumor Assays; antineoplastic agent; cabozantinib; collidine; n [5 [(6,7 dimethoxyquinolin 4 yl)oxy] 3,4,6 trimethylpyridin 2 yl] n (4 fluorophenyl)cyclopropane 1,1 dicarboxamide; n [5 [(6,7 dimethoxyquinolin 4 yl)oxy]pyridin 2 yl] n (4 fluorophenyl)cyclopropane-1,1 dicarboxamide; phosphotransferase inhibitor; pyridine; pyridine derivative; scatter factor receptor; sunitinib; unclassified drug; anilide; antineoplastic agent; cabozantinib; protein kinase inhibitor; pyridine derivative; A-549 cell line; amination; angiogenesis; animal experiment; animal model; antineoplastic activity; antiproliferative activity; Article; bromination; cancer inhibition; cell proliferation; chorioallantois; computer model; conformation; controlled study; debenzylation; drug design; drug synthesis; enzyme activity; epithelial mesenchymal transition; fluorescence activated cell sorting; Huh-7 cell line; human; human cell; IC50; liver cell carcinoma; microwave irradiation; NCI-H1299 cell line; non small cell lung cancer; nonhuman; proapoptotic activity; substitution reaction; tumor model; tumor xenograft; animal; chemical structure; disease model; dose response; drug screening; liver cell carcinoma; liver tumor; metabolism; mouse; pathology; synthesis; tumor cell line | English | 2021 | 2021-09 | 10.3390/ijms22189685 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Review | Novelty of Sphingolipids in the Central Nervous System Physiology and Disease: Focusing on the Sphingolipid Hypothesis of Neuroinflammation and Neurodegeneration | For decades, lipids were confined to the field of structural biology and energetics as they were considered only structural constituents of cellular membranes and efficient sources of energy production. However, with advances in our understanding in lipidomics and improvements in the technological approaches, astounding discoveries have been made in exploring the role of lipids as signaling molecules, termed bioactive lipids. Among these bioactive lipids, sphingolipids have emerged as distinctive mediators of various cellular processes, ranging from cell growth and proliferation to cellular apoptosis, executing immune responses to regulating inflammation. Recent studies have made it clear that sphingolipids, their metabolic intermediates (ceramide, sphingosine-1-phosphate, and N-acetyl sphingosine), and enzyme systems (cyclooxygenases, sphingosine kinases, and sphingomyelinase) harbor diverse yet interconnected signaling pathways in the central nervous system (CNS), orchestrate CNS physiological processes, and participate in a plethora of neuroinflammatory and neurodegenerative disorders. Considering the unequivocal importance of sphingolipids in CNS, we review the recent discoveries detailing the major enzymes involved in sphingolipid metabolism (particularly sphingosine kinase 1), novel metabolic intermediates (N-acetyl sphingosine), and their complex interactions in CNS physiology, disruption of their functionality in neurodegenerative disorders, and therapeutic strategies targeting sphingolipids for improved drug approaches. | Ayub, Maria; Jin, Hee-Kyung; Bae, Jae-sung | Kyungpook Natl Univ, KNU Alzheimers Dis Res Inst, Daegu 41566, South Korea; Kyungpook Natl Univ, Sch Med, Dept Physiol, Daegu 41944, South Korea; Kyungpook Natl Univ, Coll Vet Med, Dept Lab Anim Med, Daegu 41566, South Korea | Bae, Jae-sung/AAM-8663-2021; Kim, Young/T-8521-2019; Ayub, Maria/HBK-8730-2022 | 57223388486; 8088145800; 35209510400 | maria_ayub14@yahoo.com;hkjin@knmac.kr;jsbae@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 14 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.81 | 2025-07-30 | 34 | 35 | sphingolipids; sphingosine kinase 1; COX2; specialized pro-resolving lipid mediators; N-acetyl sphingosine; Alzheimer's disease | SPHINGOSINE KINASE; LIPID MEDIATORS; SPHINGOSINE-1-PHOSPHATE RECEPTORS; NEURONAL APOPTOSIS; GENE-EXPRESSION; CERAMIDE; HEALTH; METABOLISM; BRAIN; 1-PHOSPHATE | Alzheimer’s disease; COX2; N-acetyl sphingosine; Specialized pro-resolving lipid mediators; Sphingolipids; Sphingosine kinase 1 | Alzheimer Disease; Central Nervous System; Ceramides; Eicosanoids; Forecasting; Homeostasis; Humans; Inflammation; Lipoxygenase; Lysophospholipids; Membrane Lipids; Models, Biological; Nerve Degeneration; Neurodegenerative Diseases; Neuroglia; Neurons; Parkinson Disease; Phosphotransferases (Alcohol Group Acceptor); Prostaglandin-Endoperoxide Synthases; Sphingolipids; Sphingosine; cyclooxygenase 2; icosanoid; lipid; n acetyl sphingosine; phospholipid; sphingolipid; sphingosine; sphingosine kinase 1; unclassified drug; ceramide; icosanoid; lipoxygenase; lysophospholipid; membrane lipid; N-acetylsphingosine; phosphotransferase; prostaglandin synthase; sphingolipid; sphingosine; sphingosine 1-phosphate; sphingosine kinase; Alzheimer disease; amyotrophic lateral sclerosis; cell compartmentalization; health; homeostasis; human; Huntington chorea; lipogenesis; nerve degeneration; nervous system function; nervous system inflammation; neuropathology; Parkinson disease; pathology; protein acetylation; Review; signal transduction; sphingolipid metabolism; steady state; Alzheimer disease; biological model; central nervous system; degenerative disease; forecasting; glia; inflammation; metabolism; nerve cell; nerve degeneration; Parkinson disease; pathophysiology; physiology | English | 2021 | 2021-07 | 10.3390/ijms22147353 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | O-1602 Promotes Hepatic Steatosis through GPR55 and PI3 Kinase/Akt/SREBP-1c Signaling in Mice | Non-alcoholic fatty liver disease is recognized as the leading cause of chronic liver disease. Overnutrition and obesity are associated with hepatic steatosis. G protein-coupled receptor 55 (GPR55) has not been extensively studied in hepatic steatosis, although its endogenous ligands have been implicated in liver disease progression. Therefore, the functions of GPR55 were investigated in Hep3B human hepatoma cells and mice fed high-fat diets. O-1602, the most potent agonist of GPR55, induced lipid accumulation in hepatocytes, which was reversed by treatment with CID16020046, an antagonist of GPR55. O-1602 also induced intracellular calcium rise in Hep3B cells in a GPR55-independent manner. O-1602-induced lipid accumulation was dependent on the PI3 kinase/Akt/SREBP-1c signaling cascade. Furthermore, we found increased levels of lysophosphatidylinositol species of 16:0, 18:0, 18:1, 18:2, 20:1, and 20:2 in the livers of mice fed a high-fat diet for 4 weeks. One-week treatment with CID16020046 suppressed high-fat diet-induced lipid accumulation and O-1602-induced increase of serum triglyceride levels in vivo. Therefore, the present data suggest the pro-steatotic function of GPR55 signaling in hepatocytes and provide a potential therapeutic target for non-alcoholic fatty liver disease. | Kang, Saeromi; Lee, Ae-Yeon; Park, So-Young; Liu, Kwang-Hyeon; Im, Dong-Soon | Pusan Natl Univ, Coll Pharm, Busan 46241, South Korea; Kyungpook Natl Univ, Coll Pharm, BK21 FOUR KNU Community Based Intelligent Novel D, Daegu 41566, South Korea; Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Daegu 41566, South Korea; Kyung Hee Univ, Grad Sch, Coll Pharm, Dept Biomed & Pharmaceut Sci, Seoul 02447, South Korea | ; Im, Dong-Soon/AAH-9104-2020 | 55762329900; 56779308700; 57211630074; 55768214700; 24487391100 | saeromi85@gmail.com;dodo3239@naver.com;soyoung561@hanmail.net;dstlkh@gmail.com;imds@khu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 6 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.96 | 2025-07-30 | 14 | 14 | lysophosphatidylinositol; GPR55; hepatocytes; steatosis; non-alcoholic fatty liver disease | GPR55; Hepatocytes; Lysophosphatidylinositol; Non-alcoholic fatty liver disease; Steatosis | Animals; Azabicyclo Compounds; Benzoates; Calcium; Cannabidiol; Diet, High-Fat; Hep G2 Cells; Humans; Intracellular Space; Lipids; Liver; Lysophospholipids; Mice; Models, Biological; Non-alcoholic Fatty Liver Disease; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Receptors, Cannabinoid; Signal Transduction; Sterol Regulatory Element Binding Protein 1; Triglycerides; 4 (6 isopropenyl 3 methyl 2 cyclohexenyl) 5 methylresorcinol; calcium; cid 16020046; G protein coupled receptor; G protein coupled receptor 55; gastrointestinal agent; lipid; phosphatidylinositol 3 kinase; protein inhibitor; protein kinase B; sterol regulatory element binding protein 1c; triacylglycerol; unclassified drug; 4-(4-(3-hydroxyphenyl)-3-(4-methylphenyl)-6-oxo-1H,4H,5H,6H-pyrrolo(3,4-c)pyrazol-5-yl)benzoic acid; azabicyclo derivative; benzoic acid; calcium; cannabidiol; cannabinoid receptor; GPR55 protein, mouse; lipid; lysophosphatidylinositol; lysophospholipid; O-1602 compound; phosphatidylinositol 3 kinase; protein kinase B; sterol regulatory element binding protein 1; triacylglycerol; animal experiment; animal model; animal tissue; Article; body weight; calcium cell level; controlled study; enzyme phosphorylation; Hep 3B2.1-7 cell line; Hep-G2 cell line; human; human cell; lipid storage; liquid chromatography-mass spectrometry; liver cell; liver weight; male; mouse; nonalcoholic fatty liver; nonhuman; Pi3K/Akt signaling; protein expression; reverse transcription polymerase chain reaction; signal transduction; triacylglycerol blood level; Western blotting; animal; biological model; blood; chemistry; intracellular space; lipid diet; liver; metabolism; nonalcoholic fatty liver; signal transduction | English | 2021 | 2021-03 | 10.3390/ijms22063091 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | ○ | Article | OsBRKq1, Related Grain Size Mapping, and Identification of Grain Shape Based on QTL Mapping in Rice | The world population is growing rapidly, and food shortage remains a critical issue. Quantitative trait locus (QTL) mapping is a statistical analytical method that uses both phenotypic and genotypic data. The purpose of QTL mapping is to determine the exact gene location for various complex traits. Increasing grain weight is a way to increase yield in rice. Genes related to grain size were mapped using the Samgang/Nagdong double haploid (SNDH) populations. Grain sizes were diversely distributed in SNDH 113 populations, and OsBRKq1 was detected on chromosome 1 in an analysis of QTL mapping that used 1000 grain weight, grain length, and grain width. OsBRKq1 exhibited high sequence similarity with the brassinosteroid leucine-rich repeat-receptor kinases of Arabidopsis thaliana and Zea mays. It was also predicted to have a similar function because of its high homology. OsBRKq1 interacts with various grain-size control genes. Among the SNDH populations, the analysis of the relative expression level during the panicle formation stage of OsBRKq1 in panicles of SNDH117, which has the largest grain size, and SNDH6, which has the smallest grain size, the relative expression level was significantly increased in SNDH117 panicles. SNDH populations have been advancing generations for 10 years; various genetic traits have been fixed and are currently being used as bridging parents. Therefore, the stable expression level of OsBRKq1 was confirmed via QTL mapping. In the future, OsBRKq1 can be effectively used to increase the yield of rice and solve food problems by increasing the size of seeds. | Park, Jae-Ryoung; Resolus, Dany; Kim, Kyung-Min | Kyungpook Natl Univ, Sch Appl Biosci, Coll Agr & Life Sci, Div Plant Biosc, Daegu 41566, South Korea; Kyungpook Natl Univ, Coastal Agr Res Inst, Daegu 41566, South Korea; Univ Etat Haiti, Dept Crop Prod, Fac Agron & Med Vet, Natl Rd 1, Damien 1441, Port Au Prince, Haiti | ; Kim, Kyung-Min Kim/C-7007-2014 | 57211205505; 57222089995; 34868260300 | icd92@naver.com;resolusdany@yahoo.fr;kkm@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 5 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.44 | 2025-07-30 | 7 | 7 | rice; QTL; food shortage; yield; grain size; OsBRKq1 | Food shortage; Grain size; OsBRKq1; QTL; Rice; Yield | Arabidopsis; Arabidopsis Proteins; Chromosome Mapping; Chromosomes, Plant; Edible Grain; Gene Expression Regulation, Plant; Genotype; Oryza; Phenotype; Phylogeny; Protein-Serine-Threonine Kinases; Quantitative Trait Loci; Zea mays; Arabidopsis protein; At2g23950 protein, Arabidopsis; protein serine threonine kinase; agronomic trait; Arabidopsis thaliana; Article; chromosome 1; controlled study; gene expression level; gene location; genetic trait; length; maize; nonhuman; open reading frame; osbrkq1 gene; particle size; plant gene; quantitative trait locus mapping; rice; stable expression; weight; Arabidopsis; chromosomal mapping; food grain; gene expression regulation; genetics; genotype; growth, development and aging; metabolism; Oryza; phenotype; phylogeny; plant chromosome; quantitative trait locus | English | 2021 | 2021-03 | 10.3390/ijms22052289 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | ○ | Article | OSMI-1 Enhances TRAIL-Induced Apoptosis through ER Stress and NF-κB Signaling in Colon Cancer Cells | Levels of O-GlcNAc transferase (OGT) and hyper-O-GlcNAcylation expression levels are associated with cancer pathogenesis. This study aimed to find conditions that maximize the therapeutic effect of cancer and minimize tissue damage by combining an OGT inhibitor (OSMI-1) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found that OSMI-1 treatment in HCT116 human colon cancer cells has a potent synergistic effect on TRAIL-induced apoptosis signaling. Interestingly, OSMI-1 significantly increased TRAIL-mediated apoptosis by increasing the expression of the cell surface receptor DR5. ROS-induced endoplasmic reticulum (ER) stress by OSMI-1 not only upregulated CHOP-DR5 signaling but also activated Jun-N-terminal kinase (JNK), resulting in a decrease in Bcl2 and the release of cytochrome c from mitochondria. TRAIL induced the activation of NF-kappa B and played a role in resistance as an antiapoptotic factor. During this process, O-GlcNAcylation of I kappa B kinase (IKK) and I kappa B alpha degradation occurred, followed by translocation of p65 into the nucleus. However, combination treatment with OSMI-1 counteracted the effect of TRAIL-mediated NF-kappa B signaling, resulting in a more synergistic effect on apoptosis. Therefore, the combined treatment of OSMI-1 and TRAIL synergistically increased TRAIL-induced apoptosis through caspase-8 activation. Conclusively, OSMI-1 potentially sensitizes TRAIL-induced cell death in HCT116 cells through the blockade of NF-kappa B signaling and activation of apoptosis through ER stress response. | Lee, Su-Jin; Lee, Da-Eun; Choi, Soo-Young; Kwon, Oh-Shin | Kyungpook Natl Univ, Sch Life Sci, BK21 FOUR KNU Creat BioRes Grp, Daegu 41566, South Korea; Hallym Univ, Dept Biomed Sci, Chunchon 24252, South Korea; Hallym Univ, Res Inst Biosci & Biotechnol, Chunchon 24252, South Korea | 57213176234; 57192806145; 56912545700; 7402195859 | neojove79@knu.ac.kr;starkr0@knu.ac.kr;sychoi@hallym.ac.kr;oskwon@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1661-6596 | 1422-0067 | 22 | 20 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 2.51 | 2025-07-30 | 34 | 37 | O-GlcNAc transferase inhibitor; TRAIL; apoptosis; ER stress; NF-kappa B | ENDOPLASMIC-RETICULUM STRESS; INTERACTING PROTEIN; MEDIATED APOPTOSIS; OXIDATIVE STRESS; DEATH; ACTIVATION; INHIBITION; RESISTANCE; RECEPTOR; PATHWAY | Apoptosis; ER stress; NF-κB; O-GlcNAc transferase inhibitor; TRAIL | Animals; Apoptosis; Cell Line, Tumor; Colonic Neoplasms; Endoplasmic Reticulum Stress; Endoribonucleases; Enzyme Inhibitors; Humans; Mice; Mice, Nude; N-Acetylglucosaminyltransferases; NF-kappa B; Protein Serine-Threonine Kinases; Reactive Oxygen Species; Receptors, TNF-Related Apoptosis-Inducing Ligand; RNA Interference; RNA, Small Interfering; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Transcription Factor CHOP; Transplantation, Heterologous; antineoplastic agent; caspase 8; cell surface receptor; growth arrest and DNA damage inducible protein 153; I kappa B; I kappa B kinase; I kappa B kinase alpha; immunoglobulin enhancer binding protein; Janus kinase; osmi 1; protein bcl 2; stress activated protein kinase; synaptotagmin I; tumor necrosis factor related apoptosis inducing ligand; unclassified drug; enzyme inhibitor; ERN1 protein, human; growth arrest and DNA damage inducible protein 153; immunoglobulin enhancer binding protein; n acetylglucosaminyltransferase; O-GlcNAc transferase; reactive oxygen metabolite; ribonuclease; small interfering RNA; tumor necrosis factor related apoptosis inducing ligand; tumor necrosis factor related apoptosis inducing ligand receptor; animal experiment; animal model; antineoplastic activity; apoptosis; Article; cell proliferation; colon cancer; controlled study; endoplasmic reticulum stress; enzyme activity; female; HCT 116 cell line; Hep-G2 cell line; human; human cell; in vivo study; mouse; NF kB signaling; nonhuman; protein expression; synergistic effect; unfolded protein response; upregulation; animal; apoptosis; colon tumor; drug effect; endoplasmic reticulum stress; genetics; metabolism; nude mouse; pathology; RNA interference; signal transduction; tumor cell line; xenograft | English | 2021 | 2021-10 | 10.3390/ijms222011073 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Osteogenesis of 3D-Printed PCL/TCP/bdECM Scaffold Using Adipose-Derived Stem Cells Aggregates; An Experimental Study in the Canine Mandible | Three-dimensional (3D) printing is perceived as an innovative tool for change in tissue engineering and regenerative medicine based on research outcomes on the development of artificial organs and tissues. With advances in such technology, research is underway into 3D-printed artificial scaffolds for tissue recovery and regeneration. In this study, we fabricated artificial scaffolds by coating bone demineralized and decellularized extracellular matrix (bdECM) onto existing 3D-printed polycaprolactone/tricalcium phosphate (PCL/TCP) to enhance osteoconductivity and osteoinductivity. After injecting adipose-derived stem cells (ADSCs) in an aggregate form found to be effective in previous studies, we examined the effects of the scaffold on ossification during mandibular reconstruction in beagle dogs. Ten beagles were divided into two groups: group A (PCL/TCP/bdECM + ADSC injection; n = 5) and group B (PCL/TCP/bdECM; n = 5). The results were analyzed four and eight weeks after intervention. Computed tomography (CT) findings showed that group A had more diffuse osteoblast tissue than group B. Evidence of infection or immune rejection was not detected following histological examination. Goldner trichrome (G/T) staining revealed rich ossification in scaffold pores. ColI, Osteocalcin, and Runx2 gene expressions were determined using real-time polymerase chain reaction. Group A showed greater expression of these genes. Through Western blotting, group A showed a greater expression of genes that encode ColI, Osteocalcin, and Runx2 proteins. In conclusion, intervention group A, in which the beagles received the additional ADSC injection together with the 3D-printed PCL/TCP coated with bdECM, showed improved mandibular ossification in and around the pores of the scaffold. | Lee, Joon Seok; Park, Tae Hyun; Ryu, Jeong Yeop; Kim, Dong Kyu; Oh, Eun Jung; Kim, Hyun Mi; Shim, Jin-Hyung; Yun, Won-Soo; Huh, Jung Bo; Moon, Sung Hwan; Kang, Seong Soo; Chung, Ho Yun | Kyungpook Natl Univ, Sch Med, Dept Plast & Reconstruct Surg, Daegu 41944, South Korea; TINA Aesthet Surg Clin, Daegu 41938, South Korea; Kyungpook Natl Univ, Sch Med, Cell & Matrix Res Inst, Daegu 41944, South Korea; Korea Polytech Univ, Dept Mech Engn, 237 Sangidaehak Ro, Siheung Si 15073, Gyeonggi Do, South Korea; T&R Biofab Co Ltd, Res Inst, 242 Pangyo Ro, Seongnam Si 13487, Gyeonggi Do, South Korea; Pusan Natl Univ, Sch Dent, Dept Prosthodont, Dent Res Inst,Inst Translat Dent Sci, Yangsan Si 50612, South Korea; Chonnam Natl Univ, Coll Vet Med, Gwangju 61186, South Korea; Kyungpook Natl Univ, Sch Med, BK21 FOUR KNU Convergence Educ Program Biomed Sci, Daegu 41944, South Korea | LEE, JIN/Q-3108-2018; Ryu, Jeong Yeop/GLQ-9419-2022; Moon, Sung-Hwan/ABI-4375-2020 | 56496041000; 57223690181; 56366349400; 57192908794; 35746789300; 57261065200; 36487413200; 8293865200; 8424312600; 7401616696; 35435337400; 7404007181 | leejspo@knu.ac.kr;taehyeon1021@gmail.com;rjyflying@naver.com;conyong@naver.com;fullrest74@hanmail.net;sarang7939@naver.com;happyshim@kpu.ac.kr;wsyun@kpu.ac.kr;sunghwanmoon@tnrbiofab.com;neoplasia96@hanmail.net;vetkang@chonnam.ac.kr;hy-chung@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 11 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 1.84 | 2025-07-30 | 29 | 32 | adipose-derived stem cells; aggregate; osteogenesis; 3D-printed PCL; TCP; bdECM scaffold | DEMINERALIZED BONE-MATRIX; 3-DIMENSIONAL PRINTING TECHNOLOGY; INFLAMMATORY RESPONSE; TRICALCIUM PHOSPHATE; CALVARIAL DEFECT; TISSUE; SCREWS; STIMULATION; FIXATION; REPAIR | 3D-printed PCL/TCP/bdECM scaffold; Adipose-derived stem cells; Aggregate; Osteogenesis | Adipocytes; Adipose Tissue; Animals; Bone Regeneration; Calcium Phosphates; Dogs; Extracellular Matrix; Mandible; Osteoblasts; Osteogenesis; Polyesters; Printing, Three-Dimensional; Stem Cells; Tissue Engineering; Tissue Scaffolds; biomaterial; calcium phosphate; cephalosporin; collagen type 1; fibrin glue; fibrinogen; halothane; osteocalcin; polycaprolactone; thiopental; transcription factor RUNX2; calcium phosphate; polycaprolactone; polyester; adipose derived stem cell; animal cell; animal experiment; animal model; animal tissue; Article; beagle; biocompatibility; bone density; bone development; cell aggregation; collagen fiber; computer assisted tomography; connective tissue; controlled study; extracellular matrix; gene expression; histology; inflammation; jaw malformation; mandible; mandible reconstruction; nonhuman; ossification; osteoblast; real time polymerase chain reaction; staining; three dimensional printing; Western blotting; adipocyte; adipose tissue; animal; bone development; bone regeneration; chemistry; cytology; dog; drug effect; extracellular matrix; mandible; physiology; procedures; stem cell; three dimensional printing; tissue engineering; tissue scaffold | English | 2021 | 2021-06 | 10.3390/ijms22115409 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Paricalcitol Improves Hypoxia-Induced and TGF-β1-Induced Injury in Kidney Pericytes | Recently, the role of kidney pericytes in kidney fibrosis has been investigated. This study aims to evaluate the effect of paricalcitol on hypoxia-induced and TGF-beta 1-induced injury in kidney pericytes. The primary cultured pericytes were pretreated with paricalcitol (20 ng/mL) for 90 min before inducing injury, and then they were exposed to TGF-beta 1 (5 ng/mL) or hypoxia (1% O-2 and 5% CO2). TGF-beta 1 increased alpha-SMA and other fibrosis markers but reduced PDGFR beta expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-beta 1-induced cell migration of pericytes. Hypoxia increased TGF-beta 1, alpha-SMA and other fibrosis markers but reduced PDGFR beta expression in pericyte, whereas paricalcitol reversed them. Hypoxia activated the HIF-1 alpha and downstream molecules including prolyl hydroxylase 3 and glucose transporter-1, whereas paricalcitol attenuated the activation of the HIF-1 alpha-dependent molecules and TGF-beta 1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1 alpha vanished the hypoxia-induced TGF-beta 1, alpha-SMA upregulation, and PDGFR beta downregulation. The effect of paricalcitol on the HIF-1 alpha-dependent changes of fibrosis markers was not significant after the gene silencing of HIF-1 alpha. In addition, hypoxia aggravated the oxidative stress in pericytes, whereas paricalcitol reversed the oxidative stress by increasing the antioxidant enzymes in an HIF-1 alpha-independent manner. In conclusion, paricalcitol improved the phenotype changes of pericyte to myofibroblast in TGF-beta 1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1 alpha-dependent and independent manner. | Lim, Jeong-Hoon; Yook, Ju-Min; Oh, Se-Hyun; Jeon, Soo-Jee; Noh, Hee Won; Jung, Hee-Yeon; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Kim, Yong-Lim; Park, Sun-Hee | Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Internal Med, Daegu 41944, South Korea | Park, Sun-Hee/LMN-0033-2024; Lim, Jeong-Hoon/ABE-6003-2020; Cho, Jang-hee/ABD-3534-2020; Kim, Yong-Lim/AGK-3172-2022 | 55360244300; 35110084800; 56053033900; 57219960429; 57219963219; 57196396467; 7501393222; 7403536291; 8558530700; 55633533600; 7501831741 | jh-lim@knu.ac.kr;jumin18@naver.com;ttily@nate.com;hot716@naver.com;hwn1104@gmail.com;hy-jung@knu.ac.kr;jyss1002@hanmail.net;jh-cho@knu.ac.kr;drcdkim@mail.knu.ac.kr;ylkim@knu.ac.kr;sh-park@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 18 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.52 | 2025-07-30 | 9 | 9 | hypoxia; paricalcitol; pericyte; pericyte-to-myofibroblast transition; TGF-beta 1; vitamin D agonist | VITAMIN-D; RENAL INFLAMMATION; FIBROSIS; DISEASE; PROGRESSION; MECHANISMS; EXPRESSION; ORIGIN; CELLS; VDR | Hypoxia; Paricalcitol; Pericyte; Pericyte–to–myofibroblast transition; TGF-β1; Vitamin D agonist | Animals; Cells, Cultured; Ergocalciferols; Fibrosis; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney; Mice; Myofibroblasts; Oxidative Stress; Pericytes; Phosphorylation; Protective Agents; Signal Transduction; Smad2 Protein; Transforming Growth Factor beta1; alpha smooth muscle actin; carbon dioxide; glucose transporter 1; hypoxia inducible factor 1alpha; oxygen; paricalcitol; platelet derived growth factor beta receptor; procollagen proline 2 oxoglutarate 4 dioxygenase; prolyl hydroxylase 3; Smad protein; transforming growth factor beta1; unclassified drug; ergocalciferol; hypoxia inducible factor 1alpha; paricalcitol; protective agent; Smad2 protein; transforming growth factor beta1; Article; cell migration; controlled study; down regulation; drug effect; gene silencing; human; human cell; hypoxia; kidney injury; mouse; nonhuman; oxidative stress; pericyte; protein expression; Smad signaling; upregulation; animal; cell culture; fibrosis; genetics; hypoxia; kidney; metabolism; myofibroblast; pathology; pericyte; phosphorylation; signal transduction | English | 2021 | 2021-09 | 10.3390/ijms22189751 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Peroxiredoxin 1 Controls Ovulation and Ovulated Cumulus-Oocyte Complex Activity through TLR4-Derived ERK1/2 Signaling in Mice | Peroxiredoxins (PRDXs) are expressed in the ovary and during ovulation. PRDX1 activity related to the immuno-like response during ovulation is unknown. We investigated the roles of Prdx1 on TLR4 and ERK1/2 signaling from the ovulated cumulus-oocyte complex (COC) using Prdx1-knockout (K/O) and wild-type (WT) mice. Ovulated COCs were collected 12 and 16 h after pregnant mare serum gonadotropin/hCG injection. PRDX1 protein expression and COC secretion factors (Il-6, Tnfaip6, and Ptgs2) increased 16 h after ovulated COCs of the WT mice were obtained. We treated the ovulated COCs in mice with LPS (0.5 mu g/mL) or hyaluronidase (Hya) (10 units/mL) to induce TLR4 activity. Intracellular reactive oxygen species (ROS), cumulus cell apoptosis, PRDX1, TLR4/P38/ERK1/2 protein expression, and COC secretion factors' mRNA levels increased in LPS- and Hya-treated COCs. The ERK inhibitor (U0126) and Prdx1 siRNA affected TLR4/ERK1/2 expression. The number and cumulus expansion of ovulated COCs by ROS were impaired in Prdx1 K/O mice but not in WT ones. Prdx1 gene deletion induced TLR4/P38/ERK1/2 expression and cumulus expansion genes. These results show the controlling roles of PRDX1 for TLR4/P38/ERK1/2 signaling activity in ovulated mice and the interlink of COCs with ovulation. | Park, Hyo-Jin; Kim, Bokyung; Koo, Deog-Bon; Lee, Dong-Seok | Daegu Univ, Coll Engn, Dept Biotechnol, 201 Daegudae Ro, Gyongsan 38453, Gyeongbuk, South Korea; Daegu Univ, Inst Infertil, 201 Daegudae Ro, Gyongsan 38453, Gyeongbuk, South Korea; Kyungpook Natl Univ, BK21 FOUR KNU Creat BioRes Grp, Sch Life Sci, Daegu 41566, South Korea | 57198844604; 57205869587; 34974335600; 57210068061 | wh10287@naver.com;mideun@knu.ac.kr;dbkoo@daegu.ac.kr;lee1@knu.ac.kr; | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | INT J MOL SCI | 1422-0067 | 22 | 17 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CHEMISTRY, MULTIDISCIPLINARY | 2021 | 6.208 | 23.1 | 0.81 | 2025-07-30 | 12 | 14 | cumulus-oocyte complexes (COCs); extracellular signal-regulated kinase (ERK); mice; ovulation; peroxiredoxin 1 (PRDX1); toll-like receptor4 (TLR4) | GRANULOSA-CELLS; TLR4 PATHWAY; EXPRESSION; HYALURONAN; ACTIVATION; SULFIREDOXIN; INFLAMMATION; ANTIOXIDANT; RECEPTORS; CYTOKINES | Cumulus–oocyte complexes (COCs); Extracellular signal-regulated kinase (ERK); Mice; Ovulation; Peroxiredoxin 1 (PRDX1); Toll-like receptor4 (TLR4) | Animals; Cells, Cultured; Cumulus Cells; Female; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Oocytes; Ovulation; Peroxiredoxins; Toll-Like Receptor 4; cyclooxygenase 2; interleukin 6; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; peroxiredoxin 1; reactive oxygen metabolite; seric gonadotropin; small interfering RNA; toll like receptor 4; Mapk1 protein, mouse; Mapk3 protein, mouse; mitogen activated protein kinase 1; mitogen activated protein kinase 3; peroxiredoxin; Prdx1 protein, mouse; Tlr4 protein, mouse; toll like receptor 4; animal cell; animal experiment; apoptosis; Article; controlled study; enzyme activity; female; gene deletion; mouse; nonhuman; oocyte; ovulation; protein expression; real time polymerase chain reaction; signal transduction; transcription initiation; animal; C57BL mouse; cell culture; cumulus cell; cytology; genetics; knockout mouse; metabolism; oocyte; physiology | English | 2021 | 2021-09 | 10.3390/ijms22179437 | 바로가기 | 바로가기 | 바로가기 | 바로가기 |
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