• Title/Summary/Keyword: mechanism of disease

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Serine 389 phosphorylation of 3-phosphoinositide-dependent kinase 1 by UNC-51-like kinase 1 affects its ability to regulate Akt and p70 S6kinase

  • Kim, Kidae;Park, Sung Goo;Park, Byoung Chul;Kim, Jeong-Hoon;Kim, Sunhong
    • BMB Reports
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    • v.53 no.7
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    • pp.373-378
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    • 2020
  • Phosphorylation of the signaling component by protein kinase often leads to a kinase cascade or feedback loop. 3-Phosphoinositide-dependent kinase 1 (PDK1) signaling pathway diverges into various kinases including Akt and p70 S6 kinase (p70S6k). However, the PDK1 feedback mechanism remains elusive. Here, we demonstrated that UNC-51-like kinase (ULK1), an autophagy initiator kinase downstream of mechanistic target of rapamycin (mTOR), directly phosphorylated PDK1 on serine 389 at the linker region. Furthermore, our data showed that this phosphorylation affected the kinase activity of PDK1 toward downstream substrates. These results suggest a possible negative feedback loop between PDK1 and ULK1.

Physiological responses of Fucus serratus (Phaeophyceae) to high doses of cadmium exposure

  • Lee, Soon-Jeong;Cho, Mi-Young;Han, Hyun-Ja;Jee, Bo-Young;Kim, Jin-Woo
    • Journal of fish pathology
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    • v.24 no.2
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    • pp.141-152
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    • 2011
  • Growth, oxidative stress and antioxidant capacity of Fucus serratus exposed to high doses of Cd were examined. Two sites in Southwest England (Restronguet Point and Bantham Quay) were selected since they had different histories of metal contamination. 1~10 mg Cd $L^{-1}$ were treated to Aquil medium for up to 14 days. Similar levels of lipid peroxidation but different values of relative growth rates, cupric ion reducing antioxidant capacity (CUPRAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging capacity indicated that F. serratus has population-dependent antioxidant strategies. F. serratus demonstrated cadmium resistance with no visual symptoms for 14 days and the population from the polluted area seemed to have more powerful antioxidant strategies. However Fucus from the conserved area also showed protective anti oxidative mechanism.

Novel Pathogenetic Mechanism in a Clinical Isolate of Yersinia enterocolitica KU14

  • Sato Yoshinori;Kaneko Kenichi;Sasahara Takeshi;Inoue Matsuhisa
    • Journal of Microbiology
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    • v.44 no.1
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    • pp.98-105
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    • 2006
  • Yersinia enterocolitica induces a broad range of gastrointestinal syndromes, including acute enteritis. We previously reported that the clinical isolate, Y. enterocolitica KU14, which lacks pYV, was still capable of causing clinical infection. The present study demonstrated that KU14 did not trigger the death of macrophages in vitro, unlike WA-314 (ATCC51871, which harbors the pYV virulence plasmid). However, the intracellular growth of KU14 in the macrophages was greater than that of WA-C (ATCC51872, a non-plasmid harboring the derivative pYV plasmid). Treatment with a cholesterol-binding drug $(\beta-cyclodextrin)$ that affected lipid rafts resulted in a dramatic reduction in the inracellular growth of KU14. These data clearly indicate that the enhanced inracellular growth of KU14 is related to lipid raft-mediated infection.

Fluoxetine Modulates Corticostriatal Synaptic Transmission through Postsynaptic Mechanism

  • Cho, Hyeong-Seok;Choi, Se-Joon;Kim, Ki-Jung;Lee, Hyun-Ho;Cho, Young-Jin;Kim, Seong-Yun;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.1
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    • pp.31-38
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    • 2006
  • Fluoxetine, widely used for the treatment of depression, is known to be a selective serotonin reuptake inhibitor (SSRI), however, there are also reports that fluoxetine has direct effects on several receptors. Employing whole-cell patch clamp techniques in rat brain slice, we studied the effects of fluoxetine on corticostriatal synaptic transmission by measuring the change in spontaneous excitatory postsynaptic currents (sEPSC). Acute treatment of rat brain slice with fluoxetine ($10{\mu}M$) significantly decreased the amplitude of sEPSC ($8.1{\pm}3.3$%, n=7), but did not alter its frequency ($99.1{\pm}4.7$%, n=7). Serotonin ($10{\mu}M$) also significantly decreased the amplitude ($81.2{\pm}3.9$%, n=4) of sEPSC, but did not affect its frequency ($105.8{\pm}8.0$, n=4). The effect of fluoxetine was found to have the same trend as that of serotonin. We also found that the inhibitory effect of fluoxetine on sEPSC amplitude ($93.0{\pm}1.9$%, n=8) was significantly blocked, but not serotonin ($84.3{\pm}1.6$%, n=4), when the brain slice was incubated with p-chloroamphetamine ($10{\mu}M$), which depletes serotonin from the axon terminals and blocks its reuptake. These results suggest that fluoxetine inhibits corticostriatal synaptic transmission through postsynaptic, and that these effects are exerted through both serotonin dependent and independent mechanism.

Surgical Treatment of Killian-Jamieson Diverticulum

  • Kim, Dong-Chan;Hwang, Jae-Joon;Lee, Woo-Surng;Lee, Song-Am;Kim, Yo-Han;Chee, Hyun-Keun
    • Journal of Chest Surgery
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    • v.45 no.4
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    • pp.272-274
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    • 2012
  • Killian-Jamieson diverticulum is a rare diverticular disease. This disease differs from Zenker's diverticulum in its location and mechanism. Various treatment modality have been attempted, but traditional surgical treatment has been recommended for a symptomatic Killian-Jamieson diverticulum due to the concern of possible nerve injury. We performed surgical treatment by cervical incision. We report here on a case of Killian-Jamieson diverticulum and we briefly review the relevant literature.

The Effect of Mineral-induced Alkaline Reduced Water on the DSS-induced Acute Inflammatory Bowel Disease Mouse Model (알칼리환원수 음용이 급성 염증성장질환 생쥐 모델에 미치는 영향)

  • Jin, Dan;Kim, Dong-Heui;Teng, Yung-Chien;Xufeng, Qi;Lee, Kyu-Jae
    • Applied Microscopy
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    • v.38 no.2
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    • pp.81-87
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    • 2008
  • Alkaline reduced water (ARW) has been used for drinking widely in several countries of Asia. The safety and clinical effects of ARW has been reported including anti-oxidative effect and intestinal abnormal fermentation. To confirm the effect of ARW on DSS-induced acute inflammatory bowel disease (IBD) mouse model, we observed the length of total large intestine and the histopathological changes after supplying mineral induced-ARW (MARW) for 2 weeks and oral administration of 4% DSS (dextran sulfate sodium). As the result, the length of total large intestine and the disease scores by macro and microscopical access in the ARWsupplied group showed no significant differences compared with those in the control group. This result suggests that the supply of ARW for 2 weeks exerted no effect on amelioration in the DSS-induced acute IBD model. However, in consideration of the effect of ARW on the improvement of intestinal environment and gastrointestinal disease, this result seems that acute IBD animal model is not suitable or the period of ARW supply is not enough to prove the effect of ARW. The ameliorative effect of ARW on the intestinal abnormal fermentation has been confirmed by some researchers, but the precise mechanism also remain unclear. In conclusion, although MARW had no effect on the DSS-induced acute experimental colitis model, further studies on the verification of the effects of ARW by using other intestinal disease model and by long-term supply of ARW will be required. Also, It needs to clear the mechanism of ARW on the intestinal environment.

The role of de novo variants in complex and rare diseases pathogenesis

  • Rahman, Mahir;Lee, Woohyung;Choi, Murim
    • Journal of Genetic Medicine
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    • v.12 no.1
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    • pp.1-5
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    • 2015
  • De novo variants (DNVs) can arise during parental germ cell formation, fertilization, and the processes of embryogenesis. It is estimated that each individual carries 60-100 such spontaneous variants in the genome, most of them benign. However, a number of recent studies suggested that DNVs contribute to the pathogenesis of a variety of human diseases. Applications of DNVs include aiding in clinical diagnosis and identifying disease-causing genetic factors in patients with atypical symptoms. Therefore, understanding the roles of DNVs in a trio, with healthy parents and an affected offspring, would be crucial in elucidating the genetic mechanism of disease pathogenesis in a personalized manner.

New Aspects of Gene-for-Gene Interactions for Disease Resistance in Plant

  • Nam, Jaesung
    • The Plant Pathology Journal
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    • v.17 no.2
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    • pp.83-87
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    • 2001
  • Disease resistance in plants is often controlled by gene-for-gene mechanism in which avirulence (avr) gene products encoding by pathogens are specifically recognized, either directly or indirectly by plant disease resistance (R) gene products. Recent studies arising from molecular cloning of a number of R genes from various plant species that confer resistance to different pathogens and corresponding avr genes from various pathogens resulted in the accumulation of a wealth of knowledge on mode of action of gene-for-gene interaction. Specially, members of the NBS-LRR class of R genes encoding proteins containing a nucleotide binding site (NBS) and carboxyl-terminal leucine-rich repeats (LRRs) confer resistance to very different types of phytopathogens, such as bacteria, fungi, oomycetes, viruses, nematodes and aphids. This article reviewed the molecular events that occur up-stream of defense response pathway, specially, bacterial avr gene protein recognition mediated by NBS-LRR type R gene product in plant based on current research results of well studied model plants.

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Analysis of Potential Active Ingredients and Treatment Mechanism of Ponciri Fructus Immaturus for Dermatitis Accompanied by Pruritus Using Network Pharmacology (네트워크 약리학을 이용한 소양증을 동반한 피부 염증에 대한 지실(枳實)의 잠재적 치료기전 탐색)

  • Seo, GwangYeel;Kim, Jundong;Kim, Byunghyun;Kim, Kyu-Seok;Nam, Hae-jeong;Kim, Yoon-Bum
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.4
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    • pp.75-94
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    • 2022
  • Objectives : To identify the active ingredient of Poncirus Trifoliata Immaturus and to explore the mechanism expected to potentially act on dermatitis accompanied by pruritus. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of Poinciri Fructus Immaturus. We found the target protein of the selected active ingredient, disease(dermatitis accompanied by pruritus) and fexofenadine. Then we established the network between the proteins which Poinciri Fructus Immaturus and fexofenadine intersected with disease respectively, and the coregene was also extracted. After that, the active pathways in the human body involving the groups and coregenes were searched. Results : Total of 7 active ingredients were selected, and 202 target proteins were collected. There were 756 proteins related to inflammatory skin disease accompanied by pruritus, and 75 proteins were related to fexofenadine. 42 proteins crossed by Poinciri Fructus Immaturus with a disease, and 31 proteins crossed by fexofenadine with a disease. 12 proteins were found as a coregene from the proteins that cross Poinciri Fructus Immaturus and disease. Coregenes are involved in 'Nitric-oxide synthase regulator activity', 'Epidermal growth factor receptor signaling pathway'. 2 groups that extracted are invloved in 'Fc receptor signaling pathway', 'Central carbon metabolism in cancer', 'Phosphatidylinositol 3-kinase complex, class IB', and 'omega-hydroxylase P450 pathway'. Conclusion : It is expected that Poinciri Fructus Immaturus will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied by pruritus in the future. And it is also expected to have a synergy effect with fexofenadine on skin disease.

Herbal Medicines Effect on Coagulation System of Ischemic Patients (한약 투여가 허혈성 질환 환자의 혈액 응고계에 미치는 영향)

  • Lee Seoung Geun;Ryu Hyun Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.4
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    • pp.1213-1217
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    • 2004
  • Many ischemic disease patients have been taking herbal medicine and there are some papers that prescription of herbal medicine to ischemic disease patients are useful. Mechanism of herbal medicines on ischmeic disease have been investigated in many ways, but anticougulation or anti platelet effect of herbal medicines is not known obviously. And recently patients receiving anticougulation therapy are discouraged from taking herbal medicines. In this study, we investigate PT, INR, platelet of patients receiving herbal medicine therapy to study whether herbal medicines effect coagulation system of ischemic patients. In PT, INR, platelet values obtained from the patients, before and after administering herbal medicine, there were no significant changes.