• Title/Summary/Keyword: CYP

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Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis

  • Rui Chen;Mengting Wang;Qiaoling Qi;Yanli Tang;Zhenzhao Guo;Shuai Wu;Qiyan Li
    • Journal of Periodontal and Implant Science
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    • v.53 no.1
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    • pp.20-37
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    • 2023
  • Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

Therapeutic effect of Ferula assa-foetida oleo-gum resin in rats with letrozole-induced polycystic ovary syndrome

  • Amir Shieh;Seyyed Majid Bagheri;Maryam Yadegari;Davoud Javidmehr;Zeinab Farhadi
    • Clinical and Experimental Reproductive Medicine
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    • v.49 no.4
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    • pp.239-247
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    • 2022
  • Objective: Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated. Methods: Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction. Results: The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups. Conclusion: Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.

7α,25-Dihydroxycholesterol-Induced Oxiapoptophagic Chondrocyte Death via the Modulation of p53-Akt-mTOR Axis in Osteoarthritis Pathogenesis

  • Jeong-Yeon Seo;Tae-Hyeon Kim;Kyeong-Rok Kang;HyangI Lim;Moon-Chang Choi;Do Kyung Kim;Hong Sung Chun;Heung-Joong Kim;Sun-Kyoung Yu;Jae-Sung Kim
    • Molecules and Cells
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    • v.46 no.4
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    • pp.245-255
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    • 2023
  • This study aimed to exploring the pathophysiological mechanism of 7α,25-dihydroxycholesterol (7α,25-DHC) in osteoarthritis (OA) pathogenesis. 7α,25-DHC accelerated the proteoglycan loss in ex vivo organ-cultured articular cartilage explant. It was mediated by the decreasing extracellular matrix major components, including aggrecan and type II collagen, and the increasing expression and activation of degenerative enzymes, including matrix metalloproteinase (MMP)-3 and -13, in chondrocytes cultured with 7α,25-DHC. Furthermore, 7α,25-DHC promoted caspase-dependent chondrocyte death via extrinsic and intrinsic pathways of apoptosis. Moreover, 7α,25-DHC upregulated the expression of inflammatory factors, including inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2, via the production of reactive oxygen species via increase of oxidative stress in chondrocytes. In addition, 7α,25-DHC upregulated the expression of autophagy biomarkers, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3 via the modulation of p53-Akt-mTOR axis in chondrocytes. The expression of CYP7B1, caspase-3, and beclin-1 was elevated in the degenerative articular cartilage of mouse knee joint with OA. Taken together, our findings suggest that 7α,25-DHC is a pathophysiological risk factor of OA pathogenesis that is mediated a chondrocyte death via oxiapoptophagy, which is a mixed mode of apoptosis, oxidative stress, and autophagy.

Dosage Adjustment before and after Warfarin - Rifampin Combination Therapy (와파린-리팜핀 병용 시 용량 조절)

  • Kim, Dong-Hyun;Kim, Kyung-Hwan;Choi, Kyung-Hee;Lee, Kwang-Ja;Lee, Hye-Suk;Son, In-Ja;Kim, Ki-Bong;Lee, Jae-Woong;Ahn, Hyuk
    • Journal of Chest Surgery
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    • v.41 no.3
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    • pp.354-359
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    • 2008
  • Background: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin-rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. Material and Method: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan '1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). Result: The average INR of all the patient before rifampin administration was $2.25{\pm}0.52$ $(mean{\pm}SD)$, and that value for the first 100 days after rifampin administration was $1.98{\pm}0.28$. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was $2.19{\pm}0.34$, and the value after rifampin cessation was $2.49{\pm}0.43$. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. Conclusion: The warfarin dose adjustment equation of before and after warfarin-rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.

Distribution of Mast cells and Nerves in the Developing Postnatal Submandibular and Sublingual Glands of Rats (생후 발생중인 흰쥐의 턱밑샘 및 혀밑샘에서의 비만세포와 신경의 분포양상)

  • Kim, Jae-Gon;An, Soo-Hyeon;Lee, Young-Su;Baik, Byeong-Ju;Cho, Eui-Sic
    • Journal of the korean academy of Pediatric Dentistry
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    • v.26 no.2
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    • pp.350-364
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    • 1999
  • The distribution of mast cells and nerves were investigated in the submandibular and sublingual glands of postnatal rats, using morphometric, histochemical and immunohistochemical techniques. Mast cells were observed in the submandibular and sublingual glands of postnatal development. Number of mast cells gradually increased in both glands following development. At birth, mast cells were relatively fewer in submandibular gland than those in sublingual gland, and they were mainly distributed in parenchymal tissues. At $2{\sim}4$ weeks, most of the mast cells were observed in the connective tissues, surrounding neurovascular elements, but some mast cells were closely related with the acini of submandibular gland. PGP 9.5 immunoreactive nerve fibers were found in the submandibular and sublingual glands of all developmental age. The nerve fibers were showed in varicose shape, and mainly located in adjacent area of ducts and vascular components of both glands. The number of nerve fibers were increased rapidly until 8 weeks, but they were not increased any more until 24 weeks. Therefore, it is suggested that mast cells and nerve fibers related with each other, and that their interactions may play roles not only in maturation of secretory units but also growth and differentiation of the tubular structures of the rat submandibular and sublingual glands during postnatal development.

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CASE REPORTS OF TREATMENT OF ERUPTION-DISTURBED MX. FIRST MOLAR BY SURGICAL EXPOSURE (맹출 장애를 가진 상악 제1대구치의 외과적 노출을 이용한 치험례)

  • Seok, Choong-Ki;Nam, Dong-Woo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.11-18
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    • 2004
  • The eruption of permanent teeth represents the movement in the alveolar bone before appearance in oral cavity, to the occlusal plane after appearance in oral cavity, and additive movement after reaching th the occlusal plane. Tooth eruption is mostly controlled by genetic signals. The eruption stage is divided to preeruptive alveolar stage, alveolar bone stage, mucosal stage according to the process of growth and development. If the disturbance is occured in any stage of eruption, tooth does not erupt. The cause of eruption disturbance are ectopic position of the tooth germ, obstruction of the eruption path and defects in the follicle or PDL. In the treatment of eruption disturbance, surgical procedures are commonly used. There are three kind of surgical procedure ; surgical exposure, surgical repositioning, surgical exposure and traction Surgical exposure is basic procedure. This involves removal of mucosa, bone, lesion that are surrounding the teeth, dental sac when necessary to maintain a patent channel between the crown and the normal eruptive path into the oral cavity. To ensure this patency, many techniques including cementation of a celluloid crown, packing with gutta-percha or zinc oxide-eugenol, or a surgical pack, are used. When surgical exposure is conducted, operators should not expose any part of cervical root cement and not injure periodontium or root of adjunct tooth. After surgical exposure, tooth should be surrounded by keratinized gingiva. There is direct relationship between the extent of development of pathophysiologic aberrations and the intensity of the manipulative injury inflicted on the tooth by surgical treatment, so operator should consider this thing. In these cases, surgical exposure is conducted on Maxillary 1st milars that have a eruption disturbance and improve the eruption disturbance effectively.

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TREATMENT OF MALOCCLUSION, AS RELATED TO FINGER SUCKING : CASE REPORT (손가락 빨기로 인한 부정교합의 치험례)

  • Moon, Sang-Jin;Choi, Yeong-Chul
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.1-10
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    • 2004
  • The habit of finger sucking is a reflex occurring in the oral stage, due to nutritive and psychological desire. The habit of finger sucking is considered to be normal till 3 years of age. Dento-skeletal effect on maxillo-mandibular complex including occlusion is naturally correction, when habit stopped before 3 years. If finger sucking continues till $3{\sim}4$ years, Finger sucking leads to severe malocclusion and remarkable discrepancy maxillo-mandibular complex, which is difficult in expectation of natural correction. It is necessary to positive treatment. Treatment of malocclusion, as related to finger sucking is classified two methods. (psychological approach and orthodontic appliance) To stop a habit and to correct severe skeletal discrepancy and malocclusion, $fr\ddot{a}nkel$ appliance is very effective device. This study is to report two cases of treatment of malocclusion, as related to finger sucking. 2 years 10 months old girl with severe overjet, maxillo-mandibular skeletal discrepancy and severe convex facial profile was treated with a FR-II appliance. Finger sucking habit stopped immediately After 16 months, severe overjet, maxillo-mandibular skeletal discrepancy and severe convex facial profile was corrected. 4 years 2 months old girl with midline deviation, mandibular right shift, collateral posterior crossbite and facial asymmetry was treated with a FR-III appliance. Finger sucking habit stopped immediately. After 10 month, Midline deviation, mandibular right shift, collateral posterior crossbite and facial asymmetry were corrected. FR-appliance is a recommendable appliance for a habit breaker and correction of skeletal discrepancy.

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INHIBITORY EFFECT OF Er:YAG LASER ON THE GROWTH OF STREPTOCOCCUS MUTANS (Er:YAG 레이저 조사가 Streptococcus mutans의 증식억제에 미치는 효과)

  • Song, Gwang-Chul;Lee, Chang-Seop;Lee, Sang-Ho;Lee, Nan-Young
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.1
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    • pp.15-24
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    • 2003
  • The purpose of this study is to investigate the sterilization effect of Er:YAG laser against the intraoral acid producing bacterium, S. mutans, by irradiating the culture solution containing S. mutans KCTC 3065 with Er:YAG laser having a $650{\mu}m$ diameter beam through the non-contact method. We obtained the following results after examining the temperature changes of the culture solution, numbers of bacterial colonies, and acid-producing ability and attaching ability on teeth by measuring the amount of extracellular polysaccharide produced by S. mutans. The number of bacterial colony was decreased in $10{\mu}l$ culture solution irradiated with laser in overall compared to the control solution. The number decreased as the irradiation intensity and pulse repetition rate were larger and as the exposure time was increased. However, it did not change significantly in $100{\mu}l$ culture solution compared to the control solution. Although the acid-producing ability of S. mutans was inhibited for a certain duration after laser irradiation in 10r1 bacterial culture solution, it did not change in $100{\mu}m$ solution compared with the control solution. The amount of extracellular polysaccharide synthesized by S. mutans was partially decreased through laser irradiation in $10{\mu}m$ culture solution but did not change in $100{\mu}m$ culture solution. Based on these findings, we concluded that Er:YAG laser has an sterilization effect on S. mutans in which we presume that the mechanism is through the heat effect rather than the mechanical effect from development of ultrasound.

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Effect of LED mixed light conditions on the glucosinolate pathway in brassica rapa (배추 유묘의 글루코시놀레이트 합성 기작에 미치는 LED 혼합광의 효과)

  • Moon, Junghyun;Jeong, Mi Jeong;Lee, Soo In;Lee, Jun Gu;Hwang, Hyunseung;Yu, Jaewoong;Kim, Yong-Rok;Park, Se Won;Kim, Jin A
    • Journal of Plant Biotechnology
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    • v.42 no.3
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    • pp.245-256
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    • 2015
  • In the agricultural industries, LEDs are used as supplementary, as well as main lighting sources in closed cultivation systems. In cultivation using artificial light sources, various light qualities have been tried to supplement fluorescent lamps to promote plant growth and metabolism. Microarray analysis of Brassica rapa seedlings under blue and fluorescent mixed with blue light conditions identified changes in three genes of the glucosinolate pathway. This attracted attention as functional materials highly expressed 3.6-4.6 fold under latter condition. We selected four more genes of the glucosinolate pathway from the Brassica database and tested their expression changes under fluorescent light mixed with red, green, and blue, respectively. Some genes increased expression under red and blue mixed conditions. The Bra026058, Bra015379, and Bra021429; the orthologous genes of CYP79F1, ST5a, and FMOGS-OX1 in Arabidopsis, are highly expressed in Brassica rapa under fluorescent mixed with blue light conditions. Further, Bra029355, Bra034180, Bra024634, and Bra022448; the orthologous genes of MAM1, AOP3, UGT74B1, and BCAT4 in Arabidopsis, are highly expressed in Brassica rapa under fluorescent mixed with red light conditions. The various light conditions had unique effects on the varieties of Brassica, resulting in differences in glucosinolate synthesis. However, in some varieties, glucosinolate synthesis increased under mixed blue light conditions. These results will help to construct artificial light facilities, which increase functional crops production.

A Study on the Permeability Reduction Methods of the Riverbed Ground during Urban Railway Tunnel construction (도시철도터널공사 시 하저통과구간의 지반투수저하 공법에 대한 연구)

  • Kim, Joon-Jeong;Cho, Kook-Hwan;Lee, Jun-Seok
    • Proceedings of the KSR Conference
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    • 2007.11a
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    • pp.551-557
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    • 2007
  • This paper describes a study on the permeability reduction of the riverbed ground during urban railway tunnel construction. The research is mainly concentrated on the study of the grouting or injection methods among permeability reduction methods which can be adapted in the riverbed ground. Firstly, the various grouting methods are theoretically reviewed and compared based on the previous research papers and case study results. It is also evaluated the grouting methods in view of a safe construction of the river crossing railway tunnel. Baced on the literature review and previous construction data, the design technology of grouting methods considering the long term hydro-geological behaviour in the riverbed, is suggested. Two injection methods namely, Natural Durable Stabilizer(N.D.S) and Space-Multi Injaction Grouting(S.M.I) methods, are introduced as new approach methods which can be adopted to modify the riverbed ground. In order to evaluate the ground that grouted and modified by the N.D.S and S.M.I method, the pilot test programmes including the field and laboratory permeability tests, are carried out in the river crossing tunnel construction sites. The results obtained from pilot test programme, are also reviewed. In conclusion, the grouting efficiency of the S.M.I method using the non-alcalimeter silica sol is better than that of NDS method using cement. In addition, it hopes that the research results are contributed to develop the grouting design technology.

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