• BMB Reports
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• v.56 no.9
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• pp.520-525
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• 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ. Although Aβ-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aβ-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aβ accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aβ accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aβ deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression.

• BMB Reports
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• v.33 no.4
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• pp.317-320
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• 2000

The succinic semialdehyde dehydrogenase from bovine brain was inactivated by treatment with phenylglyoxal, a reagent that specifically modifies arginine residues. The inhibition at various phenylglyoxal concentrations shows pseudo-first-order kinetics with an apparent secondorder rate constant of 30 $M^{-1}min^{-1}$ for inactivation. Partial protection against inactivation was provided by the coenzyme $NAD^+$, but not by the substrate succinic semialdehyde. Spectrophotometric studies indicated that complete inactivation of the enzyme resulted from the binding of 2 mol phenylglyoxal per mol of enzyme. These results suggest that essential arginine residues, located at or near the coenzyme-binding site, are connected with the catalytic activity of brain succinic semialdehyde dehydrogenase.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.132-137
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• 2014

BACKGROUND/OBJECTIVES: In this study, the apoptogenic activity and mechanisms of cell death induced by hexane extract of aged black garlic (HEABG) were investigated in human leukemic U937 cells. MATERIALS/METHODS: Cytotoxicity was evaluated by MTT (3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide) assay. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. RESULTS: Exposure to HEABG was found to result in a concentration- and time-dependent growth inhibition by induction of apoptosis, which was associated with an up-regulation of death receptor 4 and Fas legend, and an increase in the ratio of Bax/Bcl-2 protein expression. Apoptosis-inducing concentrations of HEABG induced the activation of caspase-9, an initiator caspase of the mitochodrial mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. HEABG also induced apoptosis via a death receptor mediated extrinsic pathway by caspase-8 activation, resulting in the truncation of Bid, and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. However, pre-treatment of U937 cells with the caspase-3 inhibitor, z-DEVD-fmk, significantly blocked the HEABG-induced apoptosis of these cells, and increased the survival rate of HEABG-treated cells, confirming that HEABG-induced apoptosis is mediated through activation of caspase cascade. CONCLUSIONS: Based on the overall results, we suggest that HEABG reduces leukemic cell growth by inducing caspase-dependent apoptosis through both intrinsic and extrinsic pathways, implying its potential therapeutic value in the treatment of leukemia.

• Molecules and Cells
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• v.26 no.6
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• pp.625-630
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• 2008

This study was undertaken with the aim of developing an easy and quick means of analyzing the effect of various compounds on the synthesis and secretion of human type I collagen at the protein level. A modification of the ELISA method was used on HFF-1 cells. For the proof of concept, we used thirteen compounds most of which are known to be antioxidants. Each compound was tested at concentrations of 0, 10 and $100{\mu}m$ on HFF-1 cells for 24 h. Thirteen sets of experiments for each compound were performed in ANOVA with three replicates. Duncan multiple range test (DMRT) was used to compare the mean values obtained from the treatment groups. From the results it was concluded that Vitamin C, undecylenic acid, conjugated linoleic acid, glycolic acid, and citric acid at $100{\mu}m$ concentration could be used for anti-wrinkling or protection from premature aging, which requires enhancement of collagen synthesis. Lactic acid, EGCG, resveratrol, and retinol that can inhibit collagen synthesis effectively in a dose-dependent manner may be used for anti-fibrosis treatment purposes.

• BMB Reports
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• v.55 no.11
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• pp.547-552
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• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

• Molecules and Cells
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• v.46 no.12
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• pp.746-756
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• 2023

A recent study revealed that the loss of Deup1 expression does not affect either centriole amplification or multicilia formation. Therefore, the deuterosome per se is not a platform for amplification of centrioles. In this study, we examine whether gain-of-function of Deup1 affects the development of multiciliated ependymal cells. Our time-lapse study reveals that deuterosomes with an average diameter of 300 nm have two different fates during ependymal differentiation. In the first instance, deuterosomes are scattered and gradually disappear as cells become multiciliated. In the second instance, deuterosomes self-organize into a larger aggregate, called a deuterosome cluster (DC). Unlike scattered deuterosomes, DCs possess centriole components primarily within their large structure. A characteristic of DC-containing cells is that they tend to become primary ciliated rather than multiciliated. Our in utero electroporation study shows that DCs in ependymal tissue are mostly observed at early postnatal stages, but are scarce at late postnatal stages, suggesting the presence of DC antagonists within the differentiating cells. Importantly, from our bead flow assay, ectopic expression of Deup1 significantly impairs cerebrospinal fluid flow. Furthermore, we show that expression of mouse Deup1 in Xenopus embryos has an inhibitory effect on differentiation of multiciliated cells in the epidermis. Taken together, we conclude that the DC formation of Deup1 in multiciliated cells inhibits production of multiple centrioles.

• Journal of Korean Medical classics
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• v.24 no.5
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• pp.1-10
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• 2011

According to "Dongeuibogam(東醫寶鑑)", "the Shinnong Herb Bible(神農本草經)", "Chamdonggo(參同攷)", come to the conclusion about medical thought of "the Zhouyi Cantongxie(周易參同契)". Alchemy is a common field both on the eastern and western civilization, but a process of development is different. Ancient chinese alchemist made a study on external alchemy, but harmful consequences of external alchemy was consecutive, many scholars had turned their interest on internal alchemy which is related in human meridian biology and spirit. In the western alchemy has developed to make a study on analytic psychology and science of religion. Most importantly, the eastern and western alchemy have something in common what at the point of the perfection of self is similar, but the name is different, for example in the eastern alchemy we can be immortals and take a spiritual enlightenment with the elixir of life, in the western we can take a cure of souls as a christian. As for internal alchemy, "Cantongxie(參同契)" gives influence to the theories such as the theory of danjeon(lower part of the abdomen), evolution, aging, and life nurturing. Especially, the theory of danjeon shows such merit for studying since it is similar to triple energizers(三焦) and the theory of qi street(氣街) of oriental medicine. The study on "Cantongxie(參同契)" was achieved in Korea too, especially Chosun dynasty. "Candongkao (參同攷)" by Seo Myung-eung(徐命膺, 1716~1787) are representative. According to "Candongkao(參同攷)", Geon(乾), Gon(坤), Gam(坎), and Ri(離), the four trigrams for divination, each are affiliated with lungs, spleen, kidneys, and heart. Nowadays the study on alchemy correspond with modern trends, which are anti-aging and living without any disease. If processed mineral drugs is assured for stability, it can be used for incurable diseases such as cancer.

• Journal of Community Nutrition
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• v.2 no.1
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• pp.5-11
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• 2000

Populations both in the US and worldwide are aging. It is projected that by the year 2030 the population of Americans over 65 will increase to 70 million, more than twice their number in 1998. About one-third of elderly over the age of 65 have debilitating chronic health conditions that greatly impede their activities. Age-associated chronic diseases are believed to be associated with free radicals and the imbalance in antioxidant and oxidative stress contributes to development of several chronic health conditions. Diet and nutrients can have great impact in the health status of elderly. Several factors may contributor to the inadequate consumption of nutrients in elderly, including an inability to chew food adequately, polypharmacy, living along and limited income. Low intake of energy and several micronutrients are common among the elderly. Although overt deficiency of nutrients among the elderly is not common. a recent study showed that while elderly consume more fat, the total energy intake is low among the elderly. Inadequate intake of antioxidant nutrients such as vitamin E in elderly may contribute to the development of chronic health problems. Intake of higher than normal RDA levels of vitamin E for long periods of time has been shown to reduce the risk of many degenerative diseases, such as cardiovascular diseases(CVD) and cancer, and improve immune response in elderly. High intake of other antioxidants is also associated with reduced risk chronic diseases. Dietary antioxidants are abundant in fruits and vegetables. However, due to variety of factors, the elderly may not be able to receive these and other micronutrients through diet. Therefore, supplemental intake of micronutrients in the form of multi vitamins/minerals and/or specific micronutrients is a more practical approach to the maintenance of health status in the elderly.

• Molecules and Cells
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• v.38 no.12
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• pp.1054-1063
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• 2015

Mitochondria play a crucial role in eukaryotic cells; the mitochondrial electron transport chain (ETC) generates adenosine triphosphate (ATP), which serves as an energy source for numerous critical cellular activities. However, the ETC also generates deleterious reactive oxygen species (ROS) as a natural byproduct of oxidative phosphorylation. ROS are considered the major cause of aging because they damage proteins, lipids, and DNA by oxidation. We analyzed the chronological life span, growth phenotype, mitochondrial membrane potential (MMP), and intracellular ATP and mitochondrial superoxide levels of 33 single ETC component-deleted strains during the chronological aging process. Among the ETC mutant strains, 14 ($sdh1{\Delta}$, $sdh2{\Delta}$, $sdh4{\Delta}$, $cor1{\Delta}$, $cyt1{\Delta}$, $qcr7{\Delta}$, $qcr8{\Delta}$, $rip1{\Delta}$, $cox6{\Delta}$, $cox7{\Delta}$, $cox9{\Delta}$, $atp4{\Delta}$, $atp7{\Delta}$, and $atp17{\Delta}$) showed a significantly shorter life span. The deleted genes encode important elements of the ETC components succinate dehydrogenase (complex II) and cytochrome c oxidase (complex IV), and some of the deletions lead to structural instability of the membrane-$F_1F_0$-ATP synthase due to mutations in the stator stalk (complex V). These short-lived strains generated higher superoxide levels and produced lower ATP levels without alteration of MMP. In summary, ETC mutations decreased the life span of yeast due to impaired mitochondrial efficiency.

• Applied Microscopy
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• v.31 no.2
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• pp.117-128
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• 2001

DMF is not a good solvent for PVA. There is no solvent-PVA interaction such as H-bonding. DMF/PVA makes a UCST system. DMF/PVA makes a gel through crystallization-induced gelation. X-ray, thermal analysis, and other experimental proofs are presented. The gelation rate was faster at low temperature. Small addition of PEG increased the rate of gelation, but urea decreased the rate. SEM showed the phase demixing process very clearly. In the early stage of gelation, only phase demixing was occurring at a low rate. Hence, no holes appear in the early stage photographs. As demixing proceeded further, the holes began to appear and the sizes became bigger. DMF phase remains many holes after vaporization and PVA phase constitute the matrix phase.