• Anatomy and Cell Biology
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• v.56 no.4
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• pp.526-537
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• 2023

Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.467-473
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• 2024

In this study, we investigated the potential protective effects of (+)-afzelechin (AZC), a natural compound that is derived from Bergenia ligulata, on lipopolysaccharide (LPS)-induced inflammatory responses. AZC is known to have antioxidant, anticancer, antimicrobial, and cardiovascular protective properties. However, knowledge regarding the therapeutic potential of AZC against LPS-induced inflammatory responses is limited. Thus, we investigated the protective attributes of AZC against inflammatory damage caused by LPS exposure. We examined the effects of AZC on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). In addition, the effects of AZC on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were analyzed in the lung tissues of LPS-injected mice. Data revealed that AZC promoted the production of HO-1, inhibited the interaction between luciferase and nuclear factor (NF)-κB, and reduced the levels of COX-2/PGE2 and iNOS/NO, thereby leading to a decrease in the signal transducer and activator of transcription (STAT)-1 phosphorylation. Moreover, AZC facilitated the nuclear translocation of Nrf2, increased the binding activity between Nrf2 and the antioxidant response elements (AREs), and lowered the expression of IL-1β in the LPS-treated HUVECs. In the animal model, AZC significantly reduced the expression of iNOS in the lung tissue structure and the TNF-α level in the bronchoalveolar lavage fluid. These findings demonstrate that AZC possesses anti-inflammatory properties that regulate iNOS through the inhibition of both NF-κB expression and p-STAT-1. Consequently, AZC has potential as a future candidate for the development of new clinical substances for the treatment of pathological inflammation.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.4
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• pp.230-243
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• 2023

Objective: High temperatures can trigger cellular oxidative stress and disrupt spermatogenesis, potentially leading to male infertility. We investigated the effects of retinoic acid (RA), chitosan nanoparticles (CHNPs), and retinoic acid loaded with chitosan nanoparticles (RACHNPs) on spermatogenesis in mice induced by scrotal hyperthermia (Hyp). Methods: Thirty mice (weighing 25 to 30 g) were divided into five experimental groups of six mice each. The groups were as follows: control, Hyp induced by a water bath (43 ℃C for 30 minutes/day for 5 weeks), Hyp+RA (2 mg/kg/day), Hyp+CHNPs (2 mg/kg/72 hours), and Hyp+RACHNPs (4 mg/kg/72 hours). The mice were treated for 35 days. After the experimental treatments, the animals were euthanized. Sperm samples were collected for analysis of sperm parameters, and blood serum was isolated for testosterone measurement. Testis samples were also collected for histopathology assessment, reactive oxygen species (ROS) evaluation, and RNA extraction, which was done to compare the expression levels of the bax, bcl2, p53, Fas, and FasL genes among groups. Additionally, immunohistochemical staining was performed. Results: Treatment with RACHNPs significantly increased stereological parameters such as testicular volume, seminiferous tubule length, and testicular cell count. Additionally, it increased testosterone concentration and improved sperm parameters. We observed significant decreases in ROS production and caspase-3 immunostaining in the RACHNP group. Moreover, the expression levels of bax, p53, Fas, and FasL significantly decreased in the groups treated with RACHNPs and RA. Conclusion: RACHNPs can be considered a potent antioxidative and antiapoptotic agent for therapeutic strategies in reproductive and regenerative medicine.

• Clinical and Experimental Pediatrics
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• v.50 no.1
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• pp.28-32
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• 2007

Purpose : Human angiotensin converting enzyme (ACE) gene shows an insertion/deletion polymorphism in 16 intron, and three genotypes are determined by whether a 287 bp fragment of the DNA is present or not; II, ID and DD genotype. DD genotype has been suggested as a risk factor of chronic nephrotic disease such as IgA nephropathy and diabetic nephropathy, various cardiovascular diseases and several other diseases. ACE activity increases in acute hepatitis, chronic persistent hepatitis, chronic active hepatitis and cirrhosis. On the other hand, patients with fatty livers have normal ACE activity. This study was designed to find out the relation between polymorphsims of the ACE genes and neonatal hyperbilirubinemia in Koreans. Methods : The genomic DNA was isolated from 110 full-term Korean neonates who had hyperbilirubinemia with no obvious causes (serum bilirubin$${\geq_-}12mg/dL$$) and 164 neonates of a control population (serum bilirubin <12 mg/dL). We performed polymerase chain reaction (PCR) to see the allele of the ACE gene. Electrophoresis was done in the PCR products in 1.5 percent agarose gel, and then DNA patterns were directly visualized under ethidium bromide staining. Results : ACE genotypes in the hyperbilirubinemia group are as follows; 26.36 percent for II, 53.64 percent for ID, 20.00 percent for DD, 0.532 for I allele and 0.468 for D allele. These distributions were not significantly different from those in the control group; 24.39 percent for II, 51.83 percent for DI, 23.78 percent for DD, 0.503 for I allele and 0.497 for D allele. Conclusion : In this study, ACE gene polymorphism was detected in the neonatal hyperbilirubinemia and control group. The most frequent genotype was ID. Our results indicate that the ACE gene polymorphism is not associated with the prevalence of neonatal hyperbilirubinemia in Koreans.

• Journal of Korean Biological Nursing Science
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• v.4 no.1
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• pp.41-49
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• 2002

The purpose of this study was to identify the knowledge contents of basic nursing sciences needed by nurses in the practices of the intensive care unit(ICU). To attain the goal of this study, the nurses working at 10 hospitals in the areas of Seoul and Kangwon Province were randomly selected. They were primarily interviewed, and the open question was secondarily put to them through the questionnaire. In the process of the 1st interview, the interviewees were asked of the question, "What is the knowledge of basic sciences such as anatomy, pathology, physiology. microbiology, pharmacology and the like thought to be lacking when you communicate with doctors in the ICU and when you carry out your nursing practices in it?" The contents of the interview were tape-recorded. The period of data collection ranged from May 1, 2001 to Sept 30. The interviews were conducted with total of 20 nurses. The open-end questionnaire was secondarily mailed to nurses. 113 questionnaires were returned. 100 questionnaires except 13 ones thought to be poorly completed in content were used for data analysis. Three coders classified data obtained from the interview and the questionnaire research into 5 detailed items relating to such as anatomical physiology, pathology, pharmacology. microbiology and basics of nursing. The three coders had experiences in nursing education of 18 years, 8 years and 6 years, respectively, and of them one coder was professor in basic nursing sciences. Data were statistically treated using frequency analysis and percentage by the SAS program. As a result, the following findings were obtained : It was found that the contents that ICU nurses responded were most needed in the field of Human structure and function were water and electrolytic balance(38%), blood and circulatory system(20%), changer in the patient's skin(12%), the arrangement of the human body(10%) and the endocrine system(10%), nervous system(6%), and assessment of the state of the patient's consciousness(4%). It was found that the contents that ICU nurses responded were most needed in the field of pathology were found to be the process of the progress of the disease(32%), symptoms of the disease(27%), prognosis of the disease(22%), followed by the injury-healing process, clinical pathological examination, and examination by radiation. It was found that the contents that nurses responded were most needed in the field of pharmacology were the effect of drug(25%), the side effect of drug(22%), the relationship between diseases and drug(20%), the relationship between disease-causing bacteria and drug(20%) and chemotherapy(2%). It was found that the contents that ICU nurses responded were most needed in the field of microbiology were the relationship between diseases and disease-causing bacteria(45%), Kinds and characteristics of disease-causing bacteria(18%), infection control(16%), application of the aseptic technique(12%), isolation(9%) and the like. It was found that the basic knowledge that ICU nurses responded were needed were the identification of the patient's current state(36%), understanding of the therapeutic process(22%), the operating principle of medical equipment and instrument(20%), medical terminology(9%), equipment and instrument management(7%), calculation of the dose of injection(2%) and the like.

• Clinical and Experimental Pediatrics
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• v.49 no.1
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• pp.34-39
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• 2006

Purpose : The incidence of neonatal hyperbilirubinemia is twice as high in East Asians as in Caucasians. However, its metabolic basis has not been clearly explained. The UDP-glucuronosyltransferase gene(UGT1A1) mutation was found to be a risk factor of neonatal hyperbilirubinemia. We studied whether neonatal hyperbilirubinemia is associated with the 1828G>A(rs 10929303) polymorphism of the UGT1A1 gene, which encodes for a key enzyme of bilirubin metabolism. Methods : The genomic DNA was isolated from 80 Korean full term neonates who had greater than a 12 mg/dL level of serum bilirubin with no obvious cause, and the genomic DNA was also isolated from 164 Korean neonates of the control population. We studied a single nucleotide polymorphism (SNP) of 1828G>A in the untranslated region of the UGT1A1 gene by direct sequencing. Results : Three of the 80 neonates with a serum bilirubin level above 12 mg/dL had homozygous mutations and 10 of the 80 neonates with a serum bilirubin level above 12 mg/dL had heterozygous mutations. Thirteen of the 164 neonates of the control group had homozygous mutations and 16 neonates of the control group had heterozygous mutations. The allele frequency of 1828G>A polymorphism of UGT1A1 in the hyperbilirubinemia group was 10.0 percent, which was not significantly different from the allele frequency of 12.8 percent in the control group. Conclusion : In this study, the 1828G>A polymorphism of the UGT1A1 gene was detected in the Korean neonates with neonatal hyperbilirubinemia. Our results indicated that this SNP is not associated with the prevalence of hyperbilirubinemia in Koreans.

• Journal of Life Science
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• v.28 no.5
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• pp.605-614
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• 2018

Bee pollen has an outer wall which is resistant to both acidic and basic solutions and even the digestive enzymes in the gastrointestinal tract. Therefore, the oral bioavailability of bee pollen is only 10-15%. A previous study reported on wet-grinding technology which increased the extraction of active ingredients from bee pollen by 11 times. This study was designed to investigate the safety of wet-ground bee pollen. First, a single dose of wet-ground bee pollen was tested in both rats and beagle dogs at dosages of 5, 10, and 20 g/kg and 1.5, 3, and 6 g/kg, respectively. In rats, compound-colored stools were found in those administered 10 g/kg or more of wet-ground bee pollen. In beagle dogs, 6 g/kg of wet-ground bee pollen induced diarrhea in one male for four hours. However, no obvious clinical signs were found through the end of the experiment in rats and beagle dogs. In addition, no histological abnormality was found in all animals. The data indicates that a single dose of up to 20 g/kg of wet-ground bee pollen is safe. Next, the genetic toxicity of nano-sized bee pollen was tested. This study employed a bacterial reverse mutation test, a micronucleus assay, and a chromosomal aberration assay. In the micronucleus assay, there was no genetic toxicity up to the dosage of 2 g/kg. There was also no genetic toxicity in the bacterial reverse mutation test and chromosomal aberration assay. This data provides important information in developing nano-sized bee pollen into more advanced functional foods and herbal medicines.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

• Journal of Periodontal and Implant Science
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• v.37 no.1
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• pp.91-102
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• 2007

The long term success of periodontal treatment is dependent upon the effectiveness of the main-tenance care program after active treatment. The purpose of this study was to evaluate whether nutraceutical containing PRF-K2 as natural product from plant and seaweed has beneficial effects on clinical parameters, gingival crevicular fluid (GCF) volume and GCF cytokine levels during main- tenance phase after periodontal treatment. Among the generally healthy and non-smoking. moderate to severe chronic periodontitis patients during maintenance phase in Department of Periodontics, Chonnam National University Hospital, twenty eight patients took nutraceutical containing PRF-K2 (Oscotec Inc. Cheonan, Korea) for 3 months as experimental group and sixteen patients received only maintenance care as control group. Clinical examination and GCF collection were performed at baseline, 1, 2 and 3 months of experiment. Total amounts and concentrations of GCF IL-1{\beta}, IL-1ra and $PGE_2$ were evaluated using ELISA kit. In probing pocket depth, experimental group showed the tendency of more reduction than control group after 3 months of experiment. Sulcus bleeding index (SBI) and GCF volume were significantly decreased in experimental group(p<0.05), whereas they were increased in control group. GCF IL-1{\beta} level tended to decrease in both experimental and control group and IL-1ra concentration tended to increase in experimental group and to decrease in control group. IL-1ra/IL-1{\beta} ratio tended to increase in experimental group and to decrease in control group during experimental period. GCF $PGE_2$ amount did not show any change in experimental group and tended to increase in control group. These results suggest that nutraceutical supplement which contain PRF-K2 could improve perio-dontal condition during maintenance phase after periodontal therapy.

• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.298-305
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• 2018

Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential catalytic residues of rhomboid intramembrane serine proteases. The protein is necessary for maturation of tumor necrosis factor-alpha ($TNF-{\alpha}$) converting enzyme, which is the molecule responsible for the release of $TNF-{\alpha}$. In this study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects of the failure of $TNF-{\alpha}$ release induced by Rhbdf2 gene KO, collagen-induced arthritis (CIA), which is the representative $TNF-{\alpha}$ related disease, was induced in the Rhbdf2 mutant mouse using chicken collagen type II. The severity of the CIA was measured by traditional clinical scores and histopathological analysis of hind limb joints. A rota-rod test and grip strength test were employed to evaluate the severity of CIA based on losses of physical functions. The results indicated that Rhbdf2 mutant mice showed clear alleviation of the clinical severity of CIA as demonstrated by the significantly lower severity indexes. Moreover, a grip strength test was shown to be useful for the evaluation of physical functional losses by CIA. Overall, the results showed that the Rhbdf2 gene has a significant effect on the induction of CIA, which is related to $TNF-{\alpha}$.