• Title/Summary/Keyword: Anti-form

Search Result 691, Processing Time 0.031 seconds

Combined Therapy of Alfa-Interferon and Thymodulin on Children with Chronic Active Hepatitis B (소아의 B형 만성 활동성 간염에서 저용량 ${\alpha}$-Interferon과 Thymodulin의 병용 치료 효과)

  • Choe, Byung-Ho;Ko, Cheol-Woo
    • Pediatric Gastroenterology, Hepatology & Nutrition
    • /
    • v.1 no.1
    • /
    • pp.79-89
    • /
    • 1998
  • Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

  • PDF

Effects of Methylprednisolone on TGF-${\beta}1$, Apoptosis and Renal Scarring in Experimental Acute Pyelonephritic Weaning Rats (실험적 급성 신우신염이 유발된 이유기 백서에서 methylprednisolone이 TGF-${\beta}1$, 세포고사 및 신반흔에 미치는 영향)

  • Whang, Soo-Ja;Sung, Soon-Hee;Lee, Seung-Joo
    • Childhood Kidney Diseases
    • /
    • v.6 no.1
    • /
    • pp.75-84
    • /
    • 2002
  • Purpose Acute pyelonephritis of growing kidneys may result in renal scarring. TGF-${\beta}1$, inflammatory cytokine, has been suggested to play an important role in promoting renal scarring through apoptosis, suppression of cellular proliferation and fibrosis. We observed the effects of a potent anti-inflammatory agent, methylprednisolone on apoptosis and renal scarring in experimentally induced acute pyelonephritic weaning rats. Materials and Methods: To induce ascending pyelonephritis a saline solution containing Escherichia coli type ATCC No. 25922, pili- form (107 bacteria/mL) was infused into the bladder through the 16-guage silicone cannula for 48 hours to 102 three-week-old Sprague-Dawley rats (50-60g). Experimental groups were divided into three groups according to the treatment protocols, group I (ceftriaxone only, n=3l), group II (methylprednisolone+ceftriaxone n=28), control group (n=43) was not treated. Histopathologic scores of inflammatory changes, fibrosis and tubular atrophy, the apoptosis index and TGF-${\beta}1$ expression score were observed at post-infection 1 and 3 week. Datas were analysed using ANOVA test and P value below 0.05 was interpreted as significant. Results: The mortality rate ($21.4\%$) of group II was not different to the control group ($41.9\%$) and group I ($32.3\%$). The inflammatory score of group II ($0.8{\pm}0.87$) at week 1 was significantly lower than those of the control group ($2.3{\pm}0.87$) and Group I ($1.7{\pm}0.79$) (P<0.05). Apoptosis index of group II ($2.9{\pm}2.15$) at week 1 was significantly lower than those of the control group ($10.0{\pm}1.95$) and group 1 ($8.3{\pm}2.53$) (P<0.05). TCF-${\beta}1$ expression score of group II ($0.8{\pm}0.72$) at week 1 was significantly lower than those of the control group ($1.9{\pm}0.68$) and group I ($1.8{\pm}0.60$) (P<0.05). The fibrosis score of group II ($1.1{\pm}1.10$) at week 3 was significantly lower than that of the group I ($1.8{\pm}0.83$) (P<0.05) Conclusion: Conclusion Combined treatment with methylprednisolone and ceftriaxone reduced inflammation, fibrosis, apoptosis and TGF-${\beta}1$ expression in acute pyelonephritic weaning rats, compared to ceftriaxone alone. Anti-inflammatory agent supplemented to antibiotics could prevent renal scarring more effectively. (J Korean Soc Pediatr Nephrol 2002 ; 6 : 75-84)

  • PDF

Current Status of Children on Peritoneal Dialysis in Korea : A Cross-Sectional Multicenter Study (소아복막투석의 현황: 다기관 공동연구 결과보고)

  • Youn, Ji-Seok;Lee, Joo-Hoon;Park, Young-Seo;Yim, Hyung-Eun;Paik, Kyung-Hoon;Yoo, Kee-Hwan;Ha, Il-Soo;Cheong, Hae-Il;Choi, Yong
    • Childhood Kidney Diseases
    • /
    • v.13 no.2
    • /
    • pp.176-188
    • /
    • 2009
  • Purpose : Peritoneal dialysis (PD) is the major form of dialysis in use for infants and children with end-stage renal disease (ESRD). The aim of this study was to gain insight into the current status of children on PD in Korea. Methods : In May 2008, questionnaires were sent to the pediatric nephrologists via e-mail. Four centers replied and those data were reviewed. Results : A total of 103 patients were included in this study. Male to female ratio was 1.6:1. Mean age was $11.5{\pm}4.9$ years (0-19 years). Primary renal diseases diagnosed were as follows: primary glomerular disease (34%), chronic pyelonephritis-reflux nephropathy (14.6%), systemic disease (9.7%), renal hypoplasia/dysplasia (8.7%), heredofamilial disease (6.8%), vascular disease (3.9%), drug-induced nephropathy (1.0%), and unknown (12.6%). PD modalities were as follows: CAPD (42.7%), CCPD (27.2%), NIPD (11.7%), and Hybrid (18.4%). Weekly total Kt/V was $2.1{\pm}0.7$ (0.3-4.1). Results of peritoneal equilibrium test were as follows: low 36.8%, low average 31.6%, high average 19.7%, and high 11.8%. Z-score for weight was $-1.00{\pm}1.20$ (-4.54~+2.50). Z-score for height was $-1.55{\pm}1.65$ (-9.42~+1.87). Growth hormone was administered in 24.3% of patients. Anti-hypertensive drugs were administered in 64.0% of patients. Laboratory findings were as follows: hemoglobin $10.5{\pm}1.4$ g/dL, calcium $9.7{\pm}0.7$ mg/dL, phosphorus $5.4{\pm}1.4$ mg/dL, and parathyroid hormone $324.2{\pm}342.8$ pg/mL. Conclusion : Primary glomerular disease was the most common cause of ESRD. CAPD was the most prevalent PD modality. Low and low average peritoneal transport type were common. Growth disturbance were noted in many patients. Some patients had hypertension even with anti- hypertensive drugs. Calcium-phosphorus levels were maintained adequately, but many patients had secondary hyperparathyroidism.

Morphological and Nutritional Characteristics and Crossability with Brassica Species of Baemoochae, xBrassicoraphanus (배무채의 형태와 영양적 특성 및 교잡 친화성)

  • Lee, Soo-Seong;Kim, Tae Yoon;Yang, Jungmin;Kim, Jongkee;Lim, Sooyeon;Yoon, Moo Kyoung
    • Horticultural Science & Technology
    • /
    • v.30 no.5
    • /
    • pp.543-548
    • /
    • 2012
  • Morphological characters of Baemoochae, xBrassicoraphanus are mostly intermedium of the both parents, Chinese cabbage, Brassica rapa ssp. pekinensis and radish, Raphanus sativus. The upper and lower parts of the leaf resemble the shape of Chinese cabbage and radish, respectively. The midrib of the leaf is round like to that of radish, but very big more than 3 cm in diameter and white in color like that of Chinese cabbage. The root was changed from the swollen type like that of radish to the enlarged taproot like that of the land race of Chinese cabbage after attaining genetical stability. The flower is white. The seed pod is divided into 2 different parts; the upper part is radish and about 4 cm in length and holds 3-4 seeds and the lower part is Chinese cabbage and about 3 cm in length and holds 7-8 seeds. The color of seed is brown, weight per 1.000 seeds is 5.5 g and the number of seeds per mL is 120. The matured plant in the fall season is around 5 kg in weight and outer leaves are very vigorous and stiffly and inner leaves are erect and form a loose head. The leaf and the root contain a high level of sulforaphene which is well known as a functional substance for anti-cancer and anti-super-bacteria. Baemoochae is an amphidiploid and does not have the self incompatibility function. It has a high level of cross compatibility with Chinese cabbage as the female parent, but not the male parent. It is cross incompatible to cabbage, B. oleracea, black mustard, B. nigra and radish. However it is highly compatible to oil seed rape, B. napus, yellow mustard, B. carinata and partial compatible to muatard, B. juncea in the reciprocal cross.

The effect of two Terpenoids, Ursolic acid and Oleanolic acid on epidermal permeability barrier and simultaneously on dermal functions

  • Lim Suk Won;Jung Sung Won;Ahn Sung Ku;Kim Bora;Ryoo Hee Chang;Lee Seung Hun
    • Journal of the Society of Cosmetic Scientists of Korea
    • /
    • v.29 no.2 s.43
    • /
    • pp.205-232
    • /
    • 2003
  • Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1 mg/ml UA or 0.1-1 mg/ml ONA after tape stripping, and TEWL (Transepidermal water loss) was measured . The recovery rate increased in those UA or ONA treated groups (0.1 mg/ml UA and 0.5 mg/ml ONA) at 6 h more than $20\%$ compared to vehicle treated group (p<0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/ml per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from f week without TEWL alteration (p<0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent $(ONA{\geq}UA>Vehicle)$. LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Veh). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via $PPAR\;\alpha$. Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either $ONA\;(10{\mu}M)$ or UA $(10{\mu}M)$ for 24h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via $PPAR\;{\alpha}$. Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

The Trend of Aviation Terrorism in the 4th Industrial Revolution Period and the Development Direction for Domestic Counter Terrorism of Aviation (제4차 산업혁명 시대의 항공 테러리즘 양상 및 국내 항공테러 대응체계 발전방향)

  • Hwang, Ho-Won;Kim, Seung-Woo
    • The Korean Journal of Air & Space Law and Policy
    • /
    • v.32 no.2
    • /
    • pp.155-188
    • /
    • 2017
  • On the one hand, the 4th Industrial Revolution provides a positive opportunity to build a new civilization paradigm for mankind. However, on the other hand, due to the 4th Industrial Revolution, artificial intelligence such as 'Goggle Alpha Go' revolutionized and even the human ability was replaced with a 'Silicon Chip' as the opportunity to communicate decreases, the existence of human beings is weakened. And there is a growing concern that the number of violent crimes, such as psychopath, which hunts humans as games, will increase. Moreover, recent international terrorism is being developed in a form similar to 'Psychopathic Violent-Crime' that indiscriminately attacks innocent people. So, the probability that terrorist organizations abuse the positive effects provided by the Fourth Industrial Revolution as means of terrorism is increasing. Therefore, the paradigm of aviation terrorism is expected to change in a way that attacks airport facilities and users rather than aircraft. Because airport facilities are crowded, and psychopathic terrorists are easily accessible. From this point of view, our counter terrorism system of aviation has many weak points in various aspects such as: (1) limitations of counter-terrorism center (2) inefficient on-site command and control system (3) separated organization for aviation security consultation (4) dispersed information collection function in government (5) vulnerable to cyber attack (6) lack of international cooperation network for aviation terrorism. Consequently, it is necessary to improve the domestic counter terrorism system of aviation so as to preemptively respond to the international terrorism. This study propose the following measures to improve the aviation security system by (1) create 'Aviation Special Judicial Police' (2) revise the anti-terrorism law and aviation security law (3) Strengthening the ability respond to terrorism in cyberspace (4) building an international cooperation network for aviation terrorism.

  • PDF

The Extract from Artemisia annua Linné. Induces p53-independent Apoptosis through Mitochondrial Signaling Pathway in A549 Lung Cancer Cells (A549 폐암세포에서 미토콘드리아 경로를 통한 개똥쑥 추출물의 apoptosis 유도 효과)

  • Kim, Bo-Min;Kim, Guen-Tae;Kim, Eun-Ji;Lim, Eun-Gyeong;Kim, Sang-Yong;Kim, Young-Min
    • Journal of Life Science
    • /
    • v.26 no.8
    • /
    • pp.887-894
    • /
    • 2016
  • The extract from Artemisia annuain L.(AAE) is known as a medicinal herb that is effective against cancer. Apoptosis is the process of programmed cell death, and mitochondria are known to play a central role in cell death control. In this study, we evaluated the p53-independent apoptosis of extract of AAE through downregulation of Bcl-2 and the mitochondrial pathway in A549 (lung cancer cells). AAE may exert cancer cell apoptosis through regulating p-Akt, Cox-2, p53 and mitochondria-mediated apoptotic proteins. p-Akt/cox-2 is known to play an important role in cell proliferation and cell survival. The Bcl-2 pro-apoptotic proteins (such as Bax, Bak and Bim) mediate the permeabilization of the mitochondrial outer membrane. Treatment of AAE reduces p-Akt, p-Mdm2, cox-2 and anti-apoptotic proteins (such as Bcl-2), while tumor suppressor p53 and pro-apoptotic proteins. Activation of Bax/Bak releases cytochrome c from mitochondria to the cytosol to activate a caspase. Caspase-3 is the major effector caspase associated with apoptotic pathways. Caspase-3 generally exists in cytoplasm in the form of a pro-enzyme. In the initiation stage of apoptosis, caspase-3 is activated by proteolytic cleavage and activated caspase-3 cleaves poly (ADP-ribose) polymerase (PARP). We treated Pifithrin-α (p53 inhibitor) and Celecoxib (Cox-2 inhibitor) to learn the relationship between the signal transduction of proteins associated with apoptosis. These results suggest that AAE induces apoptosis through a p53-independent pathway in A549.

The Relationship Between Guunmong and Bok-gwae (<구운몽>과 『주역』 복괘의 관련 양상)

  • Shin, Jae-Hong
    • Journal of Korean Classical Literature and Education
    • /
    • no.38
    • /
    • pp.139-173
    • /
    • 2018
  • In the study of Guunmong, which is one of the representative classical $17^{th}$ century novels of the Joseon Dynasty, interpretations through The Book of Change(Juyeok) have recently emerged. It is necessary to more concretely investigate the themes of the research. The writer Kim man-jung wrote the work in an exile situation. In that time he composed a poem using Chinese letters with meaning connected to The book of Change. In particular, the discourse of Bok-gwae(復卦, ䷗) concentrating on the meaning of recovery might be a basis to construct the inner world of the work. The sentence of 'Bok goes well' in The Book of Change suitably match up with the hero's life in Guunmong. In addition the sentences of 'There is no illness in going and coming. So it will be no faults if friends arriver' can be applied to the meeting between the hero and heroines of Guunmong. The general declarations of The Book of Change are appropriate for explaining the contents of Guunmong. There are six Hyos that make up Gwae. The Hyos, from the first one at the bottom to the fifth one up above, connect to the characters of Guunmong. The phrase of 'Not going far away' regarding to the first Yang Hyo can be connected to Yang So-yu, hero of Guunmong. The phrase of 'Recovering beautifully' with regard to the second Eum Hyo can also be realized in the life of Jeong Gyeong-pae and Ga Chunun, two heroines of the work. The phrase of 'Danger owing to frequently recovering' regarding the third Eum Hyo can be applied to the position of Gye Seom-weol and Jeok Gyeong-hong. The phrase of 'Going middle with recovering alone' regarding the forth Eum Hyo can be matched with Sim Yo-yeon and Baek Reung-pa. The phrase of 'No regrets during an intense recovery' with regard to the fifth Eum Hyo is applicable to Yi So-hwa and Jin Chae-bong. The phrase of 'Boding of a confused recovering' regarding the sixth Eum Hyo is related to the writer's situation. The boding of confused recovering is owing to anti-royal road. The contrast between the royal road and the anti-royal road reflects Confucianism and Buddhism, dream and reality, and Yang So-yu in a dream and Seong Jin, who is same hero, in reality. Moreover, the structure of Guunmong which is organized in the form of reality-dream-reality, has a basis in this contrast. Considering these relationships, we can say the classical novel Guunmong is a fable of Bok-gwae. The work is a hopeful narration of an effective recovery that the writer anticipated in exile.

The Trend of Cigarette Design and Tobacco Flavor System Development

  • Wu, Jimmy Z.
    • Journal of the Korean Society of Tobacco Science
    • /
    • v.24 no.1
    • /
    • pp.67-73
    • /
    • 2002
  • In light of addressing consumer health concern, coping with anti-tobacco movement, and promoting new product, tobacco industry is actively pursuing to make a new generation of cigarettes with low tar and nicotine deliveries, and less harmful substances. Low tar and low nicotine cigarettes increases their market shares dramatically world wide, especially in KT&G, multinational tobacco companies, EU countries, even in China regulated by CNTC to set up yearly target to lower tar and nicotine deliveries. On the other hand, to design a new cigarette with reduced harmful substances begins to gain speed. The "modified Hoffmann list" publishes thirty plus substances in tobacco leaf and main smoke stream, which is the prime suspect causing health problems. Various ways and means are developed to reduce such components including new tobacco breeds, new curing method, tobacco leaf treatment before processing, selected filtration system, innovated casing system to reduce free radicals, as well as some non conventional cigarette products. In TSRC held this year, the main topic is related to reduce tobacco specific nitrosamines in tobacco leaf. The new generation of cigarette is in the horizon. It still needs a lot help to produce commercial products with satisfied taste and aroma characters. The flavor industry is not regulated by many governments demanding which ingredients might or might not be for tobacco use. However, most of the cigarette companies self impose a list of ingredients to guide flavor suppliers to design flavors. Unfortunately, the number of ingredients in those lists is getting shorter every year. It is understandable that the health is not the only reason. Some cigarette companies are playing safe to protect the company from potential lawsuit, while others are just copying from their competitors. Moreover, it is obvious that it needs more assistance from casings and flavors to design new generation of cigarettes with missing certain flavor components in tobacco leaf and main smoke stream. These flavor components are either non-existed or at lower level at new form of cured tobacco leaf or filtered in the main smoke stream along with reduced harmful substances. The use of carbon filters and other selected filtration system poses another tough task for flavor system design. Specific flavor components are missing from the smoke analysis data, which brings a notion of "carbon taste" and "dryness" of mouth feel. It is ever more demanded by cigarette industry to flavor suppliers to produce flavors as body enhancer, tobacco notes, salivating agents, harshness reducer, and various of aromatic notes provided they are safe to use. Another trend is that water based flavor or flavor with reduced ethanol as solvent is gaining popularity. It is preferred by some cigarette companies that the flavor is compounded with all natural ingredients or all ingredients should he GMO free. The new generation of cigarettes demands many ways of new thinking process. It is also vital for tobacco industry. It reflects the real needs for the consumers that the cigarette product should be safe to use as well as bearing the taste and aroma characters smokers always enjoyed. An effective tobacco flavor system is definitely a part of the equation. The global trend of tobacco industry is like trends of any other industries lead by consumer needs, benefited with new technology availability, affected by the global economy, and subjected for various rules and regulations. Anti-tobacco organizations and media exceptionally scrutinize cigarette, as a legal commercial product. Cigarette is probably the most studied commercial product for its composition, structure, deliveries, effects, as well as its new developmental trend. Therefore, any new trend of cigarette development would be within these boundaries. This paper is trying to point out what it would be like for tobacco industry in the next few yews and what concerns the tobacco industry. It focuses mostly on the efforts to produce safer cigarettes. It is such a vital task for the tobacco industry and its affiliate industries such as cigarette papers, filters, flavors, and other materials. The facts and knowledge presented in this paper might be well known for the public. Some of the comments and predictions are very much personal opinion for a further discussion.

Hypoxia Inducible Factor-1α Directly Regulates Nuclear Clusterin Transcription by Interacting with Hypoxia Response Elements in the Clusterin Promoter

  • Park, Jeongsook;Park, So Yun;Shin, Eunkyung;Lee, Sun Hee;Kim, Yoon Sook;Lee, Dong Hoon;Roh, Gu Seob;Kim, Hyun Joon;Kang, Sang Soo;Cho, Gyeong Jae;Jeong, Bo-Young;Kim, Hwajin;Choi, Wan Sung
    • Molecules and Cells
    • /
    • v.37 no.2
    • /
    • pp.178-186
    • /
    • 2014
  • Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.