• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.402-417
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• 2023

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22^phox, and p47^phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

• The Korea Journal of Herbology
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• v.39 no.1
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• pp.31-38
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• 2024

Objectives : Ulcerative colitis is a chronic recurrent inflammatory disease of the gastrointestinal tract. However, there are some drawbacks to long-term drug therapy such as the risk of opportunistic infections. Recently, there was an increasing interest on the use of khorasan Kamut wheat because of their higher value of selenium and fiber than modern wheat. The present study was aimed to investigate the effect of Kamut brand wheat enzyme (Kamut WE) diet on colon health in dextran sulfate sodium (DSS)-induced colitis mice. Methods : Female C57BL/6J mice were divided into 6 groups. (1) normal (Water and AIN-93G diet), (2) control (1.25% DSS and AIN-93G diet), (3) Kamut WE (1.25% DSS and Kamut WE diet), (4) normal (Water and AIN-93G diet), (5) control (2.50% DSS and AIN-93G diet), (6) Kamut WE (2.50% DSS and Kamut WE diet). Dietary intake, body weight change, disease activity index (DAI), colon length and spleen weight were monitored. Results : Kamut WE group alleviated colitis symptom, including dietary intake loss, DAI (weight loss, loose stools, bleeding), colon length shortening and spleen swelling. Further, Kamut WE diets showed a significant effect against pathological damage by the increased colon length, decreased DAI and spleen weight in DSS 1.25% as well as DSS 2.50%. Conclusions : Our study provides evidence that Kamut WE diet increased colon length, decreased DAI and spleen weight in intestinal inflammation.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.281-292
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• 2023

Background and Objectives: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold great promise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy. Methods and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances (xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM. Conclusions: To the best of our knowledge, this is the first study to show that the electrophysiological function and glycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.

• Journal of Dental Rehabilitation and Applied Science
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• v.39 no.4
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• pp.260-266
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• 2023

The concept of 'Implant Supracrestal Complex (ISC)' was introduced as a way to determine the impact of implant prosthetic design form on both short-term clinical outcomes and the long-term prognosis of bone and soft tissues around the implant. Implant-prosthesis-abutment complex design forms, such as implant-abutment design, junction, and location, can have important implications for the stable and healthy long-term maintenance of the tissues around the implant. In this case, a customized concave abutment and a prosthesis with an emergence angle of about 30 degrees were restored to a patient suffering from chronic soft tissue inflammation and pain after restoration of an implant prosthesis. It was confirmed that the new prosthesis improved complications by allowing sufficient bone and soft tissue space, achieved appropriate soft tissue sealing, and maintained the long-term stability of the implant.

• Tuberculosis and Respiratory Diseases
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• v.87 no.3
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• pp.368-377
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• 2024

Background: Bronchiectasis is a chronic respiratory disease that leads to airway inflammation, destruction, and airflow limitation, which reflects its severity. Impulse oscillometry (IOS) is a non-invasive method that uses sound waves to estimate lung function and airway resistance. The aim of this study was to assess the usefulness of IOS in predicting the severity of bronchiectasis. Methods: We retrospectively reviewed the IOS parameters and clinical characteristics in 145 patients diagnosed with bronchiectasis between March 2020 and May 2021. Disease severity was evaluated using the FACED score, and patients were divided into mild and moderate/severe groups. Results: Forty-four patients (30.3%) were in the moderate/severe group, and 101 (69.7%) were in the mild group. Patients with moderate/severe bronchiectasis had a higher airway resistance at 5 Hz (R5), a higher difference between the resistance at 5 and 20 Hz (R5-R20), a higher resonant frequency (Fres), and a higher area of reactance (AX) than patients with mild bronchiectasis. R5 ≥0.43, resistance at 20 Hz (R20) ≥0.234, R5-R20 ≥28.3, AX ≥1.02, reactance at 5 Hz (X5) ≤-0.238, and Fres ≥20.88 revealed significant univariable relationships with bronchiectasis severity (p<0.05). Among these, only X5 ≤-0.238 exhibited a significant multivariable relationship with bronchiectasis severity (p=0.039). The receiver operating characteristic curve for predicting moderate-to-severe bronchiectasis of FACED score based on IOS parameters exhibited an area under the curve of 0.809. Conclusion: The IOS assessed by the disease severity of FACED score can effectively reflect airway resistance and elasticity in bronchiectasis patients and serve as valuable tools for predicting bronchiectasis severity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.37 no.3
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• pp.17-28
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• 2024

Objectives : The aim of this study is to explore the potential of oriental medicine in managing rosacea through the regulation of the autonomic nervous system. Methods : We reviewed studies on the pathophysiology and medical treatment (both western and oriental medicine) of rosacea, as well as the relationship between rosacea and the autonomic nervous system, using four databases: PubMed, OASIS, RISS, and NDSL. Results : Rosacea is a chronic recurrent inflammatory disease characterized by symptoms such as facial flushing, inflammatory papules, and pustules. In Western medicine, symptomatic treatments like vasoconstrictors, doxycycline, and anti-inflammatory drugs are primarily used. According to the pathophysiological mechanisms of rosacea, the autonomic nervous system is closely related, particularly with sympathetic overactivity causing vasodilation and local inflammation in rosacea patients. Additionally, recent studies report that rosacea patients frequently exhibit neuropsychiatric symptoms such as anxiety, depression, and insomnia, which are closely linked to autonomic dysfunction and contribute to the worsening of skin symptoms. However, current studies on the use of oriental medicine for rosacea focus mainly on anti-inflammatory effects at the local level, similar to conventional treatments. Conclusions : Based on the close involvement of the autonomic nervous system in the pathophysiological mechanisms of rosacea and numerous studies showing that oriental medicine can effectively regulate autonomic function, applying such treatments to rosacea patients may improve not only skin symptoms but also the frequently associated neuropsychiatric symptoms like anxiety, depression and insomnia.

• Journal of Nutrition and Health
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• v.40 no.7
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• pp.606-615
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• 2007

This study was performed to investigate anti-thrombogenic, anti-inflammatory effects of n-BuOH (B) and $CH_2Cl_2$ (MC) fractions extracted from Sancho (Zanthoxylum. schinifolium) leaves in rats fed high fat diets. The experimental animal groups were consisted of eight including one 5% fat (N) and one 20% fat (H) without the test materials in diets and six H groups of feeding three levels (50, 100 and 150 mg/day) of the B and the MC fractions from Z. schinifolium, respectively. Plasma activated partial thromboplastin times and thrombin times of H group were decreased compared to the N group, but they were increased by feeding the MC fraction of 50 mg and over. Polymorphonuclear leukocyte 5#-lipo-xygenase activities and leukotriene $B_4$ contents of the H group were significantly increased compared to the N group, but they were decreased in the 100 mg and 150 mg of B fraction or the 150 mg of MC fraction fed groups. Liver cytochrome $P_{450}$, $O_2^-$, $H_2O_2$ and GSSG contents were increased by the high fat diet but decreased by feeding the B fraction or the MC fraction, while GSH content and glutathione S-transferase activity lowered by high fat diet were increased by feeding the two solvent fractions. The effects of the solvent fractions were evident at the level of 100 mg/day and over. The present results confirmed that two solvent fractions from the leaves of Z, schinifolium have enhancing effects on anti-thrombosis and anti-inflammation partly by antioxidant action and partly by direct modulation of the respective processeds. In conclusion, the n-BuOH and $CH_2Cl_2$ fractions from leaves of Z, schinifolium can be utilized as the proper ingredients of functional foods for preventing chronic degenerative disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.331-337
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• 2015

Citrus and its peels, which are by-products from juice and/or jam processing, have long been used in Asian folk medicine. Citrus peels show an abundant variety of flavanones, and these flavanones have glycone and aglycone forms. Aglycones are more potent than glycones with a variety of physiological functions since aglycone absorption is more efficient than glycones. Bioconversion with cytolase converted narirutin and naringin into naringenin and hesperidin into hesperetin. Therefore, this study aimed to investigate the anti-oxidant and anti-inflammatory effects of bioconversion of Citrus unshiu (CU) peel extracts with cytolase (CU-C) in RAW264.7 cells. HPLC chromatograms showed that CU and CU-C had 23.42% and 29.39% total flavonoids, respectively. There was substantial bioconversion of narirutin to naringenin and of hesperidin to hesperetin. All citrus peel extracts showed DPPH scavenging activities in a dose-dependent manner, and CU-C was more potent than intact CU. RAW264.7 cells were pre-treated with $0{\sim}500{\mu}g/mL$ of citrus peel extracts for 4 h and then stimulated by $1{\mu}g/mL$ of lipopolysaccharide (LPS) for 8 h. All citrus peel extracts showed decreased mRNA levels and protein expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Especially, CU-C markedly inhibited mRNA and protein expression of iNOS and COX-2 compared to intact citrus peel extracts. All citrus peel extracts showed decreased NO production by iNOS activity. This result suggests that bioconversion of citrus peel extracts with cytolase may provide potent functional food materials for prevention of chronic diseases attributable to oxidation and inflammation by boosting the anti-inflammatory effects of citrus peels.

• Journal of Life Science
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• v.24 no.12
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• pp.1339-1344
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• 2014

Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.127-135
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• 2002

Background : Idiopathic interstitial pneumonia is characterized by chronic inflammation and pulmonary fibrosis. The clara cell 10 kD protein (CC10, also designated CC16) is synthesized by the bronchial epithelium and has been suggested to have a potent anti-inflammatory effect. Therefore, CC-10 might be a candidate for controlling the inflammatory events in patients with idiopathic interstitial pneumonia. The aim of this study was to determine if the degrees of pulmonary fibrosis in idiopathic interstitial pneumonia is associated with CC-10 in the BAL fluid. Materials and Methods : The BAL fluid was collected from 29 patients and 10 controls. Densitometric analysis of the western blot assay for the CC-10 was subsequently performed. The RI (relative intensity) of each band was compared according to the diagnosis, the radiological degrees of pulmonary fibrosis and the relative proportion of inflammatory cells in the BAL fluid. Results : There were no differences in the CC-10 expression levels in the BAL fluid between the patients (RI $77.5{\pm}75.8%$) and the controls ($70.7{\pm}39.8%$) (p>0.05). In addition, the degrees of pulmonary fibrosis and airway inflammation in patients with usual interstitial pneumonia were not associated with CC-10 expression in the BAL fluid (p>0.05). Conclusion : This study suggests that CC-10 expression is not associated with the degrees of pulmonary fibrosis in patients with usual interstitial pneumonia.