• IMMUNE NETWORK
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• v.22 no.4
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• pp.34.1-34.19
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• 2022

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)₂D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.

• Molecules and Cells
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• v.47 no.3
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• pp.100033.1-100033.13
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• 2024

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

• BMB Reports
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• v.57 no.3
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• pp.161-166
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• 2024

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis.

• Tuberculosis and Respiratory Diseases
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• v.87 no.4
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• pp.494-504
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• 2024

Background: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. Methods: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. Results: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. Conclusion: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

• Journal of Ginseng Research
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• v.48 no.5
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• pp.454-463
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• 2024

Background: Panax quinquefolius L, widely recognized for its valuable contributions to medicine, has aroused considerable attention globally. Different from the extensive research has been dedicated to the root of P. quinquefolius, its berry has received relatively scant focus. Given its promising medicinal properties, this study was focused on the structural characterizations and anti-inflammatory potential of acidic polysaccharides from the P. quinquefolius berry. Materials and methods: P. quinquefolius berry was extracted with hot water, precipitated by alcohol, separated by DEAE-52-cellulose column to give a series of fractions. One of these fractions was further purified via Sephadex G-200 column to give three fractions. Then, the main fraction named as AGBP-A3 was characterized by methylation analysis, NMR spectroscopy, etc. Its anti-inflammatory activity was assessed by RAW 264.7 cell model, zebrafish model and molecular docking. Results: The main chain comprised of α-L-Rhap, α-D-GalAp and β-D-Galp, while the branch consisted mainly of α-L-Araf, β-D-Glcp, α-D-GalAp, β-D-Galp. The RAW264.7 cell assay results showed that the inhibition rates against IL-6 and IL-1β secretion at the concentration of 625 ng/mL were 24.83 %, 11.84 %, while the inhibition rate against IL-10 secretion was 70.17 % at the concentration of 312 ng/mL. In the zebrafish assay, the migrating neutrophils were significantly reduced in number, and their migration to inflammatory tissues was inhibited. Molecular docking predictions correlated well with the results of the anti-inflammatory assay. Conclusion: The present study demonstrated the structure of acidic polysaccharides of P. quinquefolius berry and their effect on inflammation, providing a reference for screening anti-inflammatory drugs.

• Korean Journal of Animal Reproduction
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• v.24 no.2
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• pp.125-142
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• 2000

13). Analysis of a purified preparation of eCG revealed that its $\beta$ -subunit consists of 149 amino acids, which was confirmed by the molecular cloning of its cDNA. There seem to be at least four to six, or even as many as 11, O-glycosylation sites on the extended C-tenninal region of the eCG $\beta$-subunit. Interestingly, eCG is a unique member of this family, as it appear to be a single molecule that possesses both LH- and FSH-like activities. Using the cDNA prepared from mRNA extracted from equine placental and pituitary tissues, we cloned the cDNA of eCG $\alpha$- and $\beta$ -subunits and eFSH $\beta$ -subunit. The mRNA expression of each subunit seems to be independently regulated, which may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. Thus, eCG is a distinct molecule from the view points of its biological function and glycoresidue structures. Recombinant eCGs including the mutants which lack oligosaccharides will be useful tools for analyzing the structure-function relationships of gonadotropins in the horse as well as other species. Similar experiments will also clarify the proposed structure and biological functions for the glycoprotein hormones. These experimental are now possible, and hopefully a resolution of the existing controversy will be forthcoming in the near future.

• Applied Biological Chemistry
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• v.20 no.2
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• pp.221-227
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• 1977

Contents of proline and chloride in halophytes were $80-1700\;{\mu}g/gfw$ and 0.13-0.45 mM/gfw respectively. The content of proline was inversely proportional to that of chloride. Rhizomes of Phargmites communis Trin, a halophyte, were grown in non-saline medium and then taken to saline treatment for one or two weeks. Growth of P. communis was inhibited when salinized with 0.25M NaCl. Total nitrogen decreased and alcohol soluble nitrogen and proline increased when growth was retarded. The quantity of Fraction 1 protein decreased at 0.25M NaCl treatment. The accumulation of proline at high concentration in P. communis suggested that it might play a role in osmotic adjustment.

• Journal of Korean Biological Nursing Science
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• v.1 no.1
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• pp.1-24
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• 1999

The purpose of this study was to define the content of requisite human structure and function knowledge needed for clinical knowledge of nursing practice. Subjects of human structure and function were divided into 10 units, and each unit was further divided into 21 subunits, resulting in a total of 90 items. Contents of knowledge of human structure and function were constructed from syllabus of basic nursing subjects in 4 college of nursing, and textbooks published by nurse scholars prepared with basic nursing sciences. The degree of need of 90 items was measured with a 4 point scale. The subjects of this study were college graduated 136 nurses from seven university hospitals in Seoul and three university hospitals located in Chonnam Province, Kyungbook Province, and Inchon. They have been working at internal medicine ward, surgical ward, intensive care unit, obstetrics and gynecology ward, pediatrics ward, opthalmology ward, ear, nose, and throat ward, emergency room, rehabilitation ward, cancer ward, hospice ward, and their working period was mostly under 5 years. The results were as follows: 1. The highest scored items of human structure and function knowledge necessary for nursing practice were electrolyte balance, blood clotting mechanism and anticoagulation mechanism, hematopoietic function, body fluid balance, function of plasma, and anatomical terminology in the order of importance. The lowest scored items of human structure and function knowledge necessary for nursing practice was sexual factors of genetic mutation. 2. The highest order of need according to unit was membrane transport in the living unit, anatomical terminology in movement and exercise unit, mechanism of hormone function in regulation and integration unit, component and function of blood in oxygenation function unit, structure and function of digestive system in digestive and energy metabolism unit, temperature regulation in temperature regulation unit electrolyte balance in body fluid and electrolyte unit, concept of immunity in body resistance unit, and genetics terminology in genetics unit. The highest order of importance according to subunit was membrane transportation in cell subunit, classification of tissues in tissue unit, function of skin and skin in skin subunit, anatomical derivatives of the skeleton subunit, classification of joints in joint subunit, an effect of exercise on muscles in muscle subunit, function of brain in nervous system subunit, special sense in sensory subunit mechanism of hormone function in endocrine subunit, structure and function of female reproductive system in reproductive system unit, structure and function of blood in blood unit, structure of heart, electrical and mechanical function in cardiovascular system unit, structure of respiratory system in respiratory system subunit, structure and function of digestive system in digestive system subunit, hormonal regulation of metabolism in nutrition and metabolism subunit, function of kidney in urologic system subunit, electolyte balance in body fluid, electolyte and acid-base balance subunit. 3. The common content of human structure and function knowledge need for all clinical areas in nursing was structure and function of blood, hematopoietic function, function of plasm, coagulation mechanism and anticoagulation mechanism, body fluid, electrolyte balance, and acid-base balance. However, the degree of need of each human structure and function knowledge was different depending on clinical areas. 4. Significant differences in human structure and function knowledge necessary for nursing practice such as skin and derivatives of the skin, growth and development of bone, classification of joint, classification of muscle, structure of muscle, function of muscle, function of spinal cord, peripheral nerve, structure and function of pancrease, component and function of blood, function of plasma, structure and function of blood, hemodynamics, respiratory dynamics, gas transport, regulation of respiration, chemical digestion of foods, absorption of foods, characteristics of nutrients, metabolism and hormonal regulation, body energy balance were demonstrated according to the duration of work. 5. Significant differences in human structure and function knowledge necessary for nursing practice such as classification of tissue, classification of muscles, function of muscles, muscle metabolism, classification of skeletal muscles, classification of nervous system, neurotransmitters, mechanism of hormone function, pituitary and pituitary hormone, structure and function of male reproductive organ, structure and function of female reproductive organ, component and function of blood, function of plasma, coagulation mechanism and anticoagulation mechanism, gas exchange, gas transport, regulation of respiration, characteristics of nutrients, energy balance, function of kidney, concept of immunity, classification and function of immunity were shown according to the work area. Based on these findings, all the 90 items constructed by Korean Academic Society of Basic Nursing Science should be included as contents of human structure and function knowledge.

• Korean Journal of Biological Psychiatry
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• v.9 no.2
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• pp.140-151
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• 2002

Object and Method:Minor physical anomalies(MPAs) are frequently seen in patients with schizophrenia. MPAs are considered to arise from the anomalous development of ectoderm-originated tissues in the developing fetus. Since the central nervous system originates from ectoderm, MPAs can be regarded as externally observable and objective indicators of the aberrant development which might have taken place in the central nervous system. To investigate whether MPAs are more frequent in schizophrenic patients, the frequencies of MPAs were compared between schizophrenic patients and normal controls. Total 245 schizophrenic patients diagnosed with DSM-IV(male : 158, female : 87), and 418 normal control subjects(male : 216, female : 202) were included in this study. The MPAs were measured using the modified Waldrop scale with fifteen items in six bodily regions; head, eye, ear, mouth, hand, and foot. Result:The total scores of Waldrop scale were $4.40{\pm}1.93$($mean{\pm}standard$ deviation) in patients and $3.43{\pm}1.68$ in controls for females, and for males, $4.58{\pm}1.75$ in patients and $4.28{\pm}1.59$ in controls. For females, the excess of MPAs in schizophrenic patients was statistically significant(t-test : p<0.001). For males, schizophrenic patients also showed more MPAs than normal controls, but this tendency did not reach statistical significance (t-test : p=0.094). When the modified Waldrop total scores excluding head circumference were compared, the total scores in schizophrenic patients were significantly higher for both male and female subjects(t-test : male p<0.001, female p=0.001). The individual anomaly items included in Waldrop scale were also investigated. The items of epicanthus, hypertelorism, malformed ears, syndactylia were significantly more frequent in schizophrenic patients. In contrast, the items of adherent ear lobes, asymmetric ears, furrowed tongue, curved fifth finger, single palmar crease and big gap between toes did not show any differences in frequency between schizophrenic patients and normal controls. Since a lot of statistical analyses showed different results between male and female subjects, it seems to be necessary to consider gender as an important controlling variable for the analysis, however only the item of head circumference showed statistically significant gender-related difference according to log-linear analysis. Conclusion:With a relatively large sample size, the frequencies of MPAs enlisted in Waldrop scale were compared between schizophrenic patients and normal controls in this study. MPAs were more frequently seen in schizophrenic patients and, especially, several specific items in the Waldrop scale showed prominent excess in schizophrenic patients. Although definite conclusions cannot be drawn due to the inherent limitation of the study using Waldrop scale, these results seem to support the possibility that aberrant neurodevelopmental process might be involved in the pathogenesis of schizophrenia in some of the patients.

• Applied Biological Chemistry
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• v.42 no.2
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• pp.116-122
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• 1999

In order to characterize the property of $Ca^{2+}$ transport in plant cell, microsomes were prepared from the roots of tomato and microsomal $^{45}Ca^{2+}$ uptake was measured. When 1 mM vanadate, a selective inhibitor of P-type ATPases, 50 mM $NO_3^-$, a specific inhibitor of vacuolar $H^{+}-ATPase$, and both of these inhibitors were treated, the microsomal $^{45}Ca^{2+}$ uptakes were inhibited by 20, 33 and 47%, respectively. The inhibitory effects of these two inhibitors were investigated by using a protonophore, gramicidin. When the chemical gradient of $H^{+}$ was relieved by gramicidin, the uptake was decreased by 30%, implying the presence of $Ca^{2+}/H^+$ antiporter in the microsomal membrane. In the $^{45}Ca^{2+}$ uptake experiment, the effect of gramicidin was independent of vanadate-induced inhibition. However, when the activity of vacuolar $H^{+}-ATPase$ was inhibited by $NO_3^-$, the effect of gramicidin was severely decreased. Meanwhile, thapsigargin, a specific antagonist of ER/SR-type $Ca^{2+}-ATPase$, inhibited the microsomal $^{45}Ca^{2+}$ uptake and the maximum inhibitory effect was obtained at $10\;{\mu}M$. The effect of thapsigargin was blocked by $NO_3^-$ and gramicidin, but not by vanadate. These results imply that vanadate directly inhibits the activity of $Ca^{2+}-ATPase$; however, $NO_3^-$ and thapsigargin block the activity of $Ca^{2+}/H^+$ antiporter by inhibiting the vacuolar $H^{+}-ATPase$. In conclusion, the microsomal $^{45}Ca^{2+}$ uptakes are mediated by two major enzymes, $Ca^{2+}-ATPase$ and $Ca^{2+}/H^+$ antiporter in tomato root tissue.