• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.453-472
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• 2022

Over the past decades, the immense clinical need for early detection methods and treatments for dementia has become a priority worldwide. The advances in PET biomarkers play increasingly important roles in understanding disease mechanisms by demonstrating the protein pathology underlying dementia in the brain. Amyloid-β and tau deposition in PET images are now key diagnostic biomarkers for the Alzheimer's disease continuum. The inclusion of biomarkers in the diagnostic criteria has achieved a paradigm shift in facilitating early differential diagnosis, predicting disease prognosis, and influencing clinical management. Furthermore, in vivo images showing pathology could become prognostic as well as surrogate biomarkers in therapeutic trials. In this review, we focus on recent developments in radiotracers for amyloid-β and tau PET imaging in Alzheimer's disease and other neurodegenerative diseases. Further, we introduce their potential application as future perspectives.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.1-15
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• 2015

Objectives The aim of this study was to investigate the effects of Cannabis Fructus on exercise capacity and cognitive function in chronic hypoperfusion induced vascular dementia rat model. Methods Vascular dementia rat models were induced by chronic cerebral hypoperfusion through bilateral common carotid arteries occlusion (BCCAO). All rats were randomly divided into 4 groups: normal group; control group; CF I group (feeding Cannabis Fructus 100 mg/kg); CF II group (feeding Cannabis Fructus 300 mg/kg). In order to study the effects of oral administration of Cannabis Fructus on vascular dementia rat models, corner turn test, hole board test, radial arm maze test, passive avoidance test were taken and Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, serum of Vascular endothelial growth factor (VEGF) protein level were measured. Also histological findings of the liver, kidney, brain and the change of Tau immunoreactive neurons in hippocampus were observed. Results CF I and CF II showed significant improvement in corner turn test, hole board test, radial arm maze test, passive avoidance test, Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, the serum of Vascular endothelial growth factor (VEGF) protein level and the change of Tau immunoreactive neurons in hippocampus. CF I showed more significant effect than CF II in these tests. However in histological observations of the liver and kidney both CF I and CF II showed glomerular injury and hepatotoxicity. Conclusions These results suggest that Cannabis Fructus was helpful in improving exercise capacity and cognitive function on Chronic hypoperfusion induced Vascular Dementia rats. However Cannabis Fructus affects the liver and kidney, therefore suggest that this is an area for further study.

• Journal of Korean Academy of Nursing
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• v.53 no.4
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• pp.371-384
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• 2023

Purpose: With an increase in the aging population, the number of patients with degenerative spinal diseases undergoing surgery has risen, as has the incidence of postoperative delirium. This study aimed to investigate the risk factors affecting postoperative delirium in older adults who had undergone spine surgery and to identify the associated biomarkers. Methods: This study is a prospective study. Data of 100 patients aged ≥ 70 years who underwent spinal surgery were analyzed. Demographic data, medical history, clinical characteristics, cognitive function, depression symptoms, functional status, frailty, and nutritional status were investigated to identify the risk factors for delirium. The Confusion Assessment Method, Delirium Rating Scale-R-98, and Nursing Delirium Scale were also used for diagnosing delirium. To discover the biomarkers, urine extracellular vesicles (EVs) were analyzed for tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light, and glial fibrillary acidic protein using digital immunoassay technology. Results: Nine patients were excluded, and data obtained from the remaining 91 were analyzed. Among them, 18 (19.8%) developed delirium. Differences were observed between participants with and without delirium in the contexts of a history of mental disorder and use of benzodiazepines (p = .005 and p = .026, respectively). Tau and UCH-L1-concentrations of urine EVs-were comparatively higher in participants with severe delirium than that in participants without delirium (p = .002 and p = .001, respectively). Conclusion: These findings can assist clinicians in accurately identifying the risk factors before surgery, classifying high-risk patients, and predicting and detecting delirium in older patients. Moreover, urine EV analysis revealed that postoperative delirium following spinal surgery is most likely associated with brain damage.

• Mass Spectrometry Letters
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• v.9 no.1
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• pp.17-23
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• 2018

Studies on the interactions of amyloidogenic proteins with trace metals, such as copper, have indicated that the metal ions perform a critical function in the early oligomerization process. Herein, we investigate the effects of Cu(II) ions on the active sequence regions of amyloidogenic proteins using electrospray ionization mass spectrometry (ESI-MS) and collision induced dissociation tandem MS (CID-MS/MS). We chose three amyloidogenic peptides NNQQNY, LYQLEN, and VQIVYK from yeast prion like protein Sup35, insulin chain A, and tau protein, respectively. [Cu-peptide] complexes for all three peptides were observed in the mass spectra. The mass spectra also show that increasing Cu(II) concentrations decrease the population of existing peptide oligomers. The tandem mass spectrum of NNQQNY shows preferential binding for the N-terminal region. All three peptides are likely to appear to be in a Cu-monomer-monomer (Cu-M-M) structure instead of a monomer-Cu-monomer (M-Cu-M) structure.

• Mass Spectrometry Letters
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• v.10 no.1
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• pp.32-37
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• 2019

The ${\pi}-{\pi}$ interactions of the peptide-dimer and peptide-trimer complexes were investigated in the (VQIVYK + LYQLEN) and (VQIVYK + NNQQNY) mixing solutions. The results showed that tyrosine (Y) residues were critical in the formation of hetero peptide-dimers and -trimers during the early oligomerization process. We used collision-induced dissociation (CID) along with electrospray ionization mass spectroscopy (ESI-MS) to obtain the structural information of the hetero-dimers and -trimers. We chose three amyloidogenic peptides-VQIVYK, NNQQNY, and LYQLEN-from tau protein, yeast prion-like protein Sup35, and insulin chain A, respectively. Hetero-dimer, -trimer, -tetramer, and -pentamer complexes were observed in the mass spectra. The tandem mass spectrum of the hetero-dimer and hetero-trimer showed two different fragmentation patterns (covalent and non-covalent bond dissociation). Y-Y interaction structures were also proposed for the hetero-dimer and -trimer complexes.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.208.1-208.1
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• 2003

In recent, growing aged people in coupled with the increased senile dementia, Alzheimer's disease, has been a social interests to be cleared out. Alzheimer Disease(AD), first reported by Alios Alzheimer (1864-1915) in 1907, is a neurodegenrative disease. Nothing exact cause of AD is available by now, but in clinical founding ${\beta}$-amyloid peptide(A${\beta}$) and microtubule associated protein($\tau$ protein) is to involved in the disease, and the most important feature in AD is Known to induce chronic inflammation to neuron cell. (omitted)

• Journal of Life Science
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• v.23 no.9
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• pp.1096-1103
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• 2013

Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.3
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• pp.284-288
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• 2005

Baker's yeast was disrupted in a 1.4-L stainless steel horizontal bead mill under a continuous recycle mode using 0.3 mm diameter zirconia beads as abrasive. A single pass in continuous mode bead mill operation liberates half of the maximally released protein. The maximum total protein release can only be achieved after passaging the cells 5 times through the disruption chamber. The degree of cell disruption was increased with the increase in feeding rate, but the total protein release was highest at the middle range of feeding rate (45 L/h). The total protein release was increased with an increase in biomass concentration from 10 to $50\%$(w/v). However, higher heat dissipation as a result of high viscosity of concentrated biomass led to the denaturation of labile protein such as glucose 6-phosphate dehydrogenase (G6PDH). As a result the highest specific activity of G6PDH was achieved at biomass concentration of $20\%$(ww/v). Generally, the degree of cell disruption and total protein released were increased with an increase in impeller tip speed, but the specific activity of G6PDH was decreased substantially at higher impeller tip speed (14 m/s). Both the degree of cell disruption and total protein release increased, as the bead loading increased from 75 to $85\% (v/v)$. Hence, in order to obtain a higher yield of labile protein such as G6PDH, the yeast cell should not be disrupted at biomass concentration and impeller tip speed higher than $20\%(w/v)$ and 10 m/s, respectively.

• Animal cells and systems
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• v.9 no.3
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• pp.161-171
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• 2005

Integrin-linked kinase 1 (ILK1) regulates several protein kinases, including PKB/Akt kinase and glycogen synthase kinase ${\beta}$. ILK1 is also involved distinctively in the cell morphological and structural functions by interacting with the components of the extracellular matrix or integrin. According to the information of serum- and glucocorticoid-induced kinase 1 (SGK1) substrate specificity (R-X-R-X-X(S/T)-${\phi};{\phi}$ indicates a hydrophobic amino acid), two putative phosphorylation sites, $Thr^{181}\;and\;Ser^{246}$, were found in ILK1. We showed that ILK1 fusion protein and two fluorescein-labeled ILK1 peptides, $FITC-^{174}RTRPRNGTLN^{183}$ and $FITC-^{239}CPRLRIFSHP^{248}$, were phosphorylated by SGK1 in vitro. We also identified that 14-3-3 ${\theta}\;{\varepsilon}\;and\;{\xi}$, among several 143-3 isotypes $({\beta},\;{\gamma},\;{\varepsilon},\;{\eta},\;{\sigma},\;{\theta},\;{\tau}\;and\;{\xi})$ formed protein complex with ILK1 in COS-1 cells. Furthermore, the phosphorylation of $Ser^{246}$ by SGK1 induced the binding with 14-3-3. It was also demonstrated that 14-3-3-bound ILK1 has reduced kinase activity. Thus, these data suggest that SGK1 phosphorylates $Thr^{181}\;and\;Ser^{246}$ of ILK1 and the phosphorylation of its $Ser^{246}$ makes ILK1 bind to 14-3-3, resulting in the inhibition of ILK1 kinase activity.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.5
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• pp.638-645
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• 2013

Interferon-tau (IFNT) is thought to be the conceptus protein that signals maternal recognition of pregnancy in ruminants. We and others have observed that OCT4 expression persists in the trophectoderm of ruminants; thus, both CDX2 and OCT4 coexist during the early stages of conceptus development. The aim of this study was to examine the effect of CDX2 and OCT4 on IFNT gene transcription when evaluated with other transcription factors. Human choriocarcinoma JEG-3 cells were cotransfected with an ovine IFNT (-654-bp)-luciferase reporter (-654-IFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with Cdx2, Ets2 and Jun increased transcription of -654-IFNT-Luc by about 12-fold compared with transfection of the construct alone. When cells were initially transfected with Oct4 (0 h) followed by transfection with Cdx2, Ets2 and/or Jun 24 h later, the expression of -654-IFNT-Luc was reduced to control levels. OCT4 also inhibited the stimulatory activity of CDX2 alone, but not when CDX2 was combined with JUN and/or ETS2. Thus, when combined with the other transcription factors, OCT4 exhibited little inhibitory activity towards CDX2. An inhibitor of the transcriptional coactivator CREB binding protein (CREBBP), 12S E1A, reduced CDX2/ETS2/JUN stimulated -654-IFNT-Luc expression by about 40%, indicating that the formation of an appropriate transcription factor complex is required for maximum expression. In conclusion, the presence of OCT4 may initially minimize IFNT expression; however, as elongation proceeds, the increasing expression of CDX2 and formation of the transcription complex leads to greatly increased IFNT expression, resulting in pregnancy establishment in ruminants.