Amino-Functionalized Mesoporous Silica Particles for Ocular Delivery of Brimonidine

Kim, Se-Na,Ko, Song Ah,Park, Chun Gwon,Lee, Seung Ho,Huh, Beom Kang,Park, Yoh Han,Kim, Young Kook,Ha, Ahnul,Park, Ki Ho,Choy, Young Bin American Chemical Society 2018 MOLECULAR PHARMACEUTICS Vol.15 No.8

<P>To treat glaucoma, conventional eye drops are often prescribed. However, the eye drops have limited effectiveness as a result of low drug bioavailability due to their rapid clearance from the preocular space. To resolve this, we proposed amino-functionalized mesoporous silica (AMS) particles as delivery carriers of the glaucoma drug, brimonidine. Because of the presence of mesopores, brimonidine (BMD) could be encapsulated in the AMS with a loading amount of 41.73 μg/mg (i.e., drug loading capacity of about 4.17%) to give the BMD-AMS, which could release the drug in a sustained manner over 8 h. BMD-AMS was also shown to be mucoadhesive due to the presence of both hydroxyl and amino groups in the surface, allowing for formation of hydrogen bonds and an ionic complex with the mucin, respectively. Therefore, when topically administered to rabbit eyes in vivo, BMD-AMS could reside in the preocular space for up to 12 h because of its adherence to the mucous layer. To assess in vivo efficacy, we examined the variance in intraocular pressure (IOP) and brimonidine concentration in the aqueous humor (AH) after applying BMD-AMS to the eye, which was compared with that induced by Alphagan P, the marketed brimonidine eye drops. For BMD-AMS, the duration in the decrease in IOP and the area under the drug concentration in the AH-time curve (AUC) were 12 h and 2.68 μg·h/mL, respectively, which were about twice as large as those obtained with Alphagan P; this finding indicated enhanced ocular bioavailability of brimonidine with BMD-AMS.</P> [FIG OMISSION]</BR>

Effect of High Fructose Corn Syrup (HFCS) Intake on the Female Reproductive Organs and Lipid Accumulation in Adult Rats

Ko, Eun-Ah,Kim, Hye-Ri,Kim, Yong-Bin,Kim, Hee-Su,Lee, Sung-Ho The Korean Society of Developmental Biology 2017 발생과 생식 Vol.21 No.2

High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats.

자연치유적 접근방식에 의한 치매의 전인치유 모델

( Ko Woon Sil ),( Kim Jung Ah ),( Ko Han Chul ),( An Kyung Up ) 인문사회과학예술융합학회 2022 인문사회과학예술융합학회지 Vol.6 No.1

치매는 노화로 인해 인류가 직면한 과제로, 가장 심각한 정신 건강 문제 중 하나입니다. 2020년 기준으로, 치매 인구는 65세 이상 노인 인구의 15.8%를 占합니다. 질병관리본부와 보건복지부는 '3가지 권장(운동, 식사, 독서), 3가지 금기(금연, 뇌손상, 약물남용), 3가지 실천(건강검진, 소통, 조기치매 발견)' 등 치매예방의 중요성을 강조합니다. 인공지능 시대에 치매는 개인의 문제가 아니라 가족적 노력을 준비하며 함께 걱정하고 해결해야 할 사회적 질병입니다. 미세 뇌기능 장애 단계에서 치매 예방이 필요하며, 미세 뇌기능 장애를 적극적으로 발견할 수 있는 융합 관리 방법, 생활 습관, 운동 방법 등 자연 치유 방법이 대안으로 살펴볼 수 있습니다. 이를 위해 기억력 상실로 치매 예방을 위한 생활 방식과 자연 치유를 사용하는 전인적인 모델이 필요다고 믿습니다. Dementia is a challenge faced by mankind due to aging and is one of the most serious mental health problems. As of 2020, the dementia population accounted for 15.8% of the 65-year-old elderly population. The Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare also value the importance of preventing dementia, such as three recommendations, exercise, eating, reading, three taboo items, abstinence from smoking, brain damage, and three implementations, health checkups, communication, and early detection of dementia. In the era of artificial intelligence, dementia is not an individual problem, but a disease that society must worry about and solve together in preparation for family efforts. There is a need to prevent dementia in the stage of mild cognitive impairment. Therefore, natural healing methods such as convergence management methods, lifestyle habits, and exercise methods that actively discovered mild cognitive impairment can be seen as an alternative. To this end, it is believed that a whole-person model using lifestyle and natural healing is needed to prevent dementia from losing memory.

Identification and characterization of arginase II as a chondrocyte phenotype-specific gene

Ko, Ah-Ra*,Huh, Yun-Hyun*,Lee, Hyun-Chae,Song, Woo-Keun,Lee, Young-Sup,Chun, Jang-Soo Taylor Francis 2006 IUBMB life Vol.58 No.10

<P>We have previously shown that activation of extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) causes chondrocyte dedifferentiation, which contributes to the destruction of arthritic cartilage. In the present study, we identified genes involved in the ERK1/2 regulation of chondrocyte dedifferentiation. Several genes were identified by subtractive hybridization, and, of these, arginase II was selected for further functional characterization. Similar to the pattern of type II collagen expression, which is a hallmark of chondrocyte differentiation, arginase II expression was increased during chondrogenesis of mesenchymal cells. The high expression level of arginase II was decreased during dedifferentiation of chondrocytes, whereas its expression was restored during redifferentiation of the dedifferentiated chondrocytes. Inhibition of ERK1/2 signaling in chondrocytes enhanced type II collagen expression with a concomitant increase in expression and activity of arginase II. However, ectopic expression of arginase II or inhibition of its activity did not affect chondrocyte differentiation. The results collectively indicate that expression of arginase II is specific to the chondrocyte phenotype, although the expression of arginase II alone is not sufficient for articular chondrocytes to maintain a differentiated phenotype.</P><P>iubmb<I>Life</I>, 58: 597–605, 2006</P>

The Differential DRP1 Phosphorylation and Mitochondrial Dynamics in the Regional Specific Astroglial Death Induced by Status Epilepticus

Ko, Ah-Reum,Hyun, Hye-Won,Min, Su-Ji,Kim, Ji-Eun Frontiers Media S.A. 2016 Frontiers in cellular neuroscience Vol.10 No.-

<P>The response and susceptibility to astroglial degenerations are relevant to the distinctive properties of astrocytes in a hemodynamic-independent manner following status epilepticus (SE). Since impaired mitochondrial fission plays an important role in mitosis, apoptosis and programmed necrosis, we investigated whether the unique pattern of mitochondrial dynamics is involved in the characteristics of astroglial death induced by SE. In the present study, SE induced astroglial apoptosis in the molecular layer of the dentate gyrus, accompanied by decreased mitochondrial length. In contrast, clasmatodendritic (autophagic) astrocytes in the CA1 region showed mitochondrial elongation induced by SE. Mdivi-1 (an inhibitor of mitochondrial fission) effectively attenuated astroglial apoptosis, but WY14643 (an enhancer of mitochondrial fission) aggravated it. In addition, Mdivi-1 accelerated clasmatodendritic changes in astrocytes. These regional specific mitochondrial dynamics in astrocytes were closely correlated with dynamin-related protein 1 (DRP1; a mitochondrial fission protein) phosphorylation, not optic atrophy 1 (OPA1; a mitochondrial fusion protein) expression. To the best of our knowledge, the present data demonstrate for the first time the novel role of DRP1-mediated mitochondrial fission in astroglial loss. Thus, the present findings suggest that the differential astroglial mitochondrial dynamics may participate in the distinct characteristics of astroglial death induced by SE.</P>

Gene Expression Related to Cognitive Function in Growth Hormone-treated Mice with Prader-Willi Syndrome

Ko, Ah-Ra Association for Research of MPS and Rare Diseases 2016 Journal of mucopolysaccharidosis and rare disease Vol.2 No.2

Prader-Willi syndrome (PWS) is a rare genetic disorder often caused by a deletion of the chromosome 15q11-q13 region inherited from the father or by maternal disomy 15. Growth hormone deficiency with short stature, hypogonadism, cognitive and behavioral problems, analgesia, decreased gastric motility and decreased ability to vomit with hyperphagia are common in PWS leading to severe obesity in early childhood, if not controlled. The goal of this study is to investigate the effects of recombinant human GH (rhGH, henceforth designated GH) on the gene expression related to cognitive function in the brain of PWS mouse model (Snord116del). GH restored the mRNA expression level of several genes in the cerebellum. These data suggest the effect of GH on the expression of cognitive function related genes in cerebellum may provide a mechanism for the GH-induced brain function in PWS patients.

Chromosome Aberrations in Porcine Embryo Produced by Nuclear Transfer with Somatic Cell

Ah, Ko-Seung,Jin, Song-Sang,Tae, Do-Jeong,Chung, Kil-Saeng,Lee, Hoon-Taek 한국수정란이식학회 2002 한국수정란이식학회 학술대회 Vol.2002 No.1

Nuclear transfer (NT) techniques have advanced in the last years, and cloned animals have been produced by using somatic cells in several species including pig. However, it is difficult that the nuclear transfer porcine embryos development to blastocyst stage overcoming the cell block in vitro. Abnormal segregation of chromosomes in nuclear transferred embryos on genome activation stage bring about embryo degeneration, abnormal blastocyst, delayed and low embryo development. Thus, we are evaluated that the correlations of the frequency of embryo developmental rates and chromosome aberration in NT and In viかo fertilization (IVF) derived embryo. We are used for ear-skin-fibroblast cell in NT. If only karyotyping of embryonic cells are chromosomally abnormal, they may difficultly remain undetected. Then, we evaluate the chromosome aberrations, fluorescent in situ hybridization (FISH) with porcine chromosome 1 submetacentric specific DNA probe were excuted. In normal diploid cell nucleus, two hybridization signal was detected. In contrast, abnormal cell figured one or three over signals. The developmental rates of NT and IVF embryos were 55% vs 63%, 32% vs 33% and 13% vs 17% in 2 cell, 8 cell and blastocyst, respectively. When looking at the types of chromosome aberration, the detection of aneuploidy at Day 3 on the embryo culture. The percentage of chromosome aneuploidy of NT and IVF at 4-cell stage 40.0%, 31.3%, respectively. This result indicate that chromosomal abnormalities are associated with low developmental rate in porcine NT embryo. It is also suggest that abnormal porcine embryos produced by NT associated with lower implantation rate, increase abortion rate and production of abnormal fetuses.

Mannitol induces selective astroglial death in the CA1 region of the rat hippocampus following status epilepticus

( Ah Reum Ko ),( Tae Cheon Kang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.9

In the present study, we addressed the question of whether treatment with mannitol, an osmotic diuretic, affects astrogliovascular responses to status epilepticus (SE). In saline-treated animals, astrocytes exhibited reactive astrogliosis in the CA1-3 regions 2-4 days after SE. In the mannitol-treated animals, a large astroglial empty zone was observed in the CA1 region 2days after SE. This astroglial loss was unrelated to vasogenic edema formation. There was no difference in SE-induced neuronal loss between saline- and mannitol-treated animals. Furthermore, mannitol treatment did not affect astroglial loss and vasogenic edema formation in the dentate gyrus and the piriform cortex. These findings suggest that mannitol treatment induces selective astroglial loss in the CA1 region independent of vasogenic edema formation following SE. These findings support the hypothesis that the susceptibility of astrocytes to SE is most likely due to the distinctive heterogeneity of astrocytes independent of hemodynamics. [BMB Reports 2015; 48(9): 507-512]

Chromosome Aberrations in Porcine Embryo Produced by Nuclear Transfer with Somatic Cell

Ko, Seung Ah,Song, Sang Jin,Do Jeong Tae,Chung, Kil Saeng,Lee, Hoon Taek 충남대학교 형질전환복제돼지연구센터 2004 논문집 Vol. No.8

The Feasibility of Assessing the Diets of Minke Whale (Balaenoptera acutorostrata) in the East Sea through Fatty Acid Composition in Blubber and Stable Isotopic Ratio of Skin

Ko, Ah-Ra,Ju, Se-Jong,Choi, Seok-Gwan,Shin, Kyung-Hoon Korean Ocean Research & Development Institute and 2016 OCEAN SCIENCE JOURNAL Vol.51 No.3

To track the diet of minke whale (Balaenoptera acutorostrata) in the East Sea (Japan Sea), a conjoint analysis of fatty acids and C and N stable isotopes was performed on blubber and skin from the whale and its potential prey. The total lipid content in the blubber of minke whales ranged from 37.9% to 82.7% of wet mass (mean <TEX>${\pm}SD$</TEX>, <TEX>$63.1{\pm}17.2%$</TEX>), with triacylglycerols being the dominant lipids (96.9%-99.2% of total lipids). The lipid and fatty acid (FA) contents were systematically stratified throughout the depth of the blubber layers; contents of the dominant monounsaturated FAs (MUFAs), including <TEX>$18:1{\omega}9$</TEX> and <TEX>$16:1{\omega}7$</TEX>, increased from the innermost layer to the outermost layer, whereas contents of saturated FAs (SFAs) and polyunsaturated FAs (PUFAs) were higher in the innermost layer than in the outermost layer. This stratification is related to the different physiological roles of the blubber layers; e.g., thermoregulation, streaming, and buoyancy. A comparison of the FA compositions of the innermost layer of minke whales with those of potential prey indicates that FA compositions in the whales are similar to those of Pacific herring. In addition, stable isotope ratios(<TEX>${\delta}^{13}C$</TEX> and <TEX>${\delta}^{15}N$</TEX>) suggest that minke whale and Pacific herring have the same or similar diets. Therefore, the diets of minke whale from the East Sea (Japan Sea) could be inferred from information on the diet of the Pacific herring, although FA compositions and stable isotope ratios for Pacific herring would not exactly reflect the whale's diet. Although the very limited number of samples was used in this study, our preliminary findings are very promising to help understand the feeding ecology of minke whales in the East Sea (Japan Sea).