• 제목/요약/키워드: Pathogenic mechanisms

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Molecular and Cellular Basis of Neurodegeneration in Alzheimer's Disease

  • Jeong, Sangyun
    • Molecules and Cells
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    • 제40권9호
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    • pp.613-620
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    • 2017
  • The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid ${\beta}-peptide$ ($A{\beta}$) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than $A{\beta}$ plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD. A growing amount of evidence suggests that soluble $A{\beta}$ oligomers in concert with hyperphosphorylated tau (pTau) serve as the major pathogenic drivers of neurodegeneration in AD. Increased $A{\beta}$ oligomers trigger neuronal dysfunction and network alternations in learning and memory circuitry prior to clinical onset of AD, leading to cognitive decline. Furthermore, accumulated damage to mitochondria in the course of aging, which is the best-known nongenetic risk factor for AD, may collaborate with soluble $A{\beta}$ and pTau to induce synapse loss and cognitive impairment in AD. In this review, I summarize and discuss the current knowledge of the molecular and cellular biology of AD and also the mechanisms that underlie $A{\beta}-mediated$ neurodegeneration.

Inhibition of Red Ginseng on 5-Hydroxyeicosatetraenoic Acid (5-HETE) Biosynthesis from Arachidonic Acid in Helicobacter Pylori-infected Gastric Cells

  • Park Soo-Jin
    • Nutritional Sciences
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    • 제9권3호
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    • pp.152-158
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    • 2006
  • Helicobacter pylori (H. pylori) infection rapidly stimulated either COX-2 or 5-LOX and released arachidonic acid metabolites that have been considered as pivotal mediators in H. pylori-induced inflammatory responses. To determine whether red ginseng extract (RGE) can suppress the biosynthesis of 5(S)-hydroxyeicosatetraenoic acids (HETE), a precursor metabolite of leukotrienes B4 (LTB4) in H. pylori-provoked inflammatory responses in gastric epithelial cells, the biosynthesis of monohydroxy fatty acids was measured using radioactive arachidonic acid and validated by RP-HPLC using non-radioactive AA as substrate in AGS cells cocultured with H. pylori (ATCC 43504) with or without pretreatment of RGE. Among three known major HETEs, H. pylori infection specifically induced the biosynthesis of $^{14}C-5(S)-HETE$ rather than the complex of $^{14}C-15S-/^{14}C-12(S)-HETE$ from $^{14}C-AA$, concomitantly obtained by HPLC(p<0.01). RGE, 1 to $100{\mu}g/ml$, selectively suppressed H. pylori-stimulated $^{14}C-5(S)-HETE$ production implying the attenuation of 5-lipoxygenase activity, of which was similar to known LOX inhibitor NDGA $(10{\mu}M)$ (p<0.01). However, the amount of 5(S)-HETE was significantly reduced by higher dose of RGE $(100{\mu}g/ml)$ (p<0.05). These results indicated that LOX pathway might be one of principle pathogenic mechanisms of H. pylori and red ginseng could be a nutraceutical against H. pylori infection through inhibiting action of LOX activity.

천막상부 뇌수막종 절제후 단기간에 발생한 두개인두종 - 증례보고 - (Rapidly Evolving Craniopharyngioma after Resection of Supratentorial Meningioma - Case Report -)

  • 김성수;고용;이형중;김영수;오성훈;김광명;오석전
    • Journal of Korean Neurosurgical Society
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    • 제30권10호
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    • pp.1220-1223
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    • 2001
  • Authors experienced a unique case of craniopharyngioma which had evolved rapidly after 4 years of total resection for supratentorial meningioma. A 58-year-old woman presented with headache and visual deterioration. Previously, she had undertaken surgical removal of frontal convexity meningioma 4 years ago and had been well without any postoperative sequelae thereafter. Brain magnetic resonance imaging demonstrated a newly developed suprasellar mass. Pertinent operative procedure was performed and histological verification was made as an adamantinomatous craniopharyngioma. She has been showing unremarkable clinical course up to date. Possible pathogenic mechanisms of de novo development of craniopharyngioma are disscussed with review of case.

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Multi-host Pathogenesis by Pseudomonas aeruginosa and Use of Drosophila melanogaster as a New Model Host

  • Cho You-Hee;Lau Gee;Rahme Laurence
    • 한국미생물학회:학술대회논문집
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    • 한국미생물학회 2002년도 추계학술대회
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    • pp.40-50
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    • 2002
  • Fruit fly, Drosophila melanogaster has developed efficient immune mechanisms to prevent microbial infection, which are consisted of cellular and humoral responses. During the systemic or local infection, two distinct pathways (Toll and Imd) play major roles in antimicrobial peptide synthesis. The Toll pathway is required to defend Gram-positive bacterial and fungal infections, whereas the Imd pathway is important in Gram-negative bacterial infection. We have shown that the infection of the opportunistic Gram-negative bacterium, Pseudomonas aeruginosa strain PA14 (PA14) into fly dorsal thorax can kill the flies within 48 h ($100\%$ mortality) in our optimized infection condition, suggesting that the PA14 strain can cause disease progress in fly model system. We found that flies carrying a constitutively activated mutant form of the Toll receptor $(Tl^{10b})$ showed increased resistance to P. aeruginosa infection and that flies carrying mutations in the Toll signaling pathway as well as in the Imd signaling pathway was more susceptible to PA14 infection. All these results imply that the Toll pathway might be important in the resistance to this pathogenic Gram-negative bacterial infection.

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잔디 Large patch의 생물학적 방제를 위한 길항 미생물의 선발과 항균력 검정 (Antimicrobial test of Antagonistic Microbes for Biological Control of Large patch of Zoysiagrass)

  • 마기윤;이긍주
    • 한국잔디학회:학술대회논문집
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    • 한국잔디학회 2011년도 제24차 정기총회 및 학술발표회
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    • pp.35-35
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    • 2011
  • A large patch disease caused by Rhizoctonia solani AG2-2(IV) is a serious problem in turfgrass sites including golf courses and sports fields in Korea. The objectives of this study were to isolate some antagonistic microorganisms and to explain some involving mechanisms. Initially single colonies which were formed from the filtrates of various soil samples were obtained from LB culture and then co-cultured with R.solani AG2-2(IV) on PDA plate to explore some antagonistic microbes against for large patch fungus, Rhizoctonia solani AG2-2(IV). Out of total 82 antagonistic isolates which commonly had inhibition effect on Rhizoctonia solani AG2-2(IV) mycelial growth, one candidate (YPIN22) showed the most antifungal effect, which was confirmed by the longest distance from the edge of bacterial colony to the mycelial edge of the Rhizoctonia solani AG2-2(IV) in the dual culture. A succeeding investigation was to test any potential effect of the isolate on growth inhibition of 5 other turfgrass pathogens including R. solani solani AG2-2(IIIB), P. ultimum, C. caudatum, C. lunata, and F.oxysporum. Preliminary result indicated that the new isolate YPIN22 was also found to have antagonistic potential on the growth inhibition of those turfgrass pathogenic fungi, which was explained by inhibition zones ranging from 8 to 22mm. A further explanation of some characteristics of the isolate YPIN22 will be discussed in detail.

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Analysis of Biological Experiments on the Anti-inflammatory and Antipyretic Effects of Hwangryeonhaedok-tang

  • Kim, Jung-Hoon;Shin, Hyeun-Kyoo
    • 대한한의학회지
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    • 제33권4호
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    • pp.26-36
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    • 2012
  • Objectives: To establish scientific and objective evidence for the use of a Korean medicine, articles regarding Hwangryeonhaedok-tang (HRHDT), a herbal medicine frequently used in Korean medical clinics and hospitals, were gathered and analyzed. Methods: The articles were classified as being from domestic or international journals, and by their year of publication. The mechanisms of the anti-inflammatory and antipyretic effects of HRHDT were investigated. Results: Of the 25 articles analyzed, 7 were published from Korea, 7 were from China, and 11 were from Japan. HRHDT showed anti-inflammatory and antipyretic effects through the regulation of the expression of Th1 cytokines including interleukin-2 (IL-2), IL-8, interferon-${\gamma}$ (IFN-${\gamma}$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$); and Th2 cytokines including IL-4, IL-6, and IL-12, which inhibit leukotriene B4 (LTB4), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inflammatory cells. It also lowered preprodynorphin (PPD), and corticotropin-releasing factor (CRF) in the peripheral nerve system and hypothalamus. Conclusions: We speculate that the anti-inflammatory and antipyretic effects could be related to the therapeutic efficacy of HRHDT in removing pathogenic fire and heat.

생강 저장굴에서 발생한 건강 피해 (Health hazards occurred in the underground storing places of ginger roots)

  • 임현술;김헌;배근량;김두희
    • 농촌의학ㆍ지역보건
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    • 제23권2호
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    • pp.251-258
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    • 1998
  • Ginger has been cultivated for thousands of years. It is very popular in the food industry as an additive to ginger ale, candies, pastries and cakes. The root has a strong, sweet scent. It contains protein, fat, carbohydrates, ash, calcium, potassium, vitamin A. thiamine, riboflavin, niacin and ascorbic acid. In korea, farmers keep ginger roots into underground holes from the harvest time to the seedtime. They dig 6 meters under the ground and preserve the cultivated ginger roots. This study was conducted to evaluate the health hazards occurred in the underground storing places of ginger roots. Authors reviewed the accidents occurred in those places, therefore transported by the public emergency system in Seo-cheon city from Jan, 1 1996 to Dec, 31 1997. We could confirm 8 persons on transport records. Among them, 5 persons were due to poisoning, 3 persons were due to injuries. We would like to suggest that poisoning could be induced by hypoxia and injuries occurred from a fall into the underground hole. These should be prevented by the health education for farmers. And further investigations are needed to understand their magnitude and the pathogenic mechanisms.

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Sclerotiorin: a Novel Azaphilone with Demonstrated Membrane Targeting and DNA Binding Activity against Methicillin-Resistant Staphylococcus aureus

  • Dasagrandhi, Chakradhar;Pandith, Anup;Imran, Khalid
    • 한국미생물·생명공학회지
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    • 제48권4호
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    • pp.429-438
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    • 2020
  • The emergence of multi-drug resistant, pathogenic methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health and has created a need for novel functional therapeutic agents. In this study, we evaluated the underlying mechanisms of the anti-MRSA effect of an azaphilone pigment, sclerotiorin (SCL) from Penicillium sclerotiorum. The antimicrobial activity of SCL was evaluated using agar disc diffusion, broth microdilution, time-kill assays and biophysical studies. SCL exhibits selective activity against Gram positive bacteria including MRSA (range, MIC = 128-1028 ㎍/ml) and exhibited rapid bactericidal action against MRSA with a > 4 log reduction in colony forming units within three hours of administration. Biophysical studies, using fluorescent probes and laser or electron microscopy, demonstrated a SCL dose-dependent alternation in membrane potential (62.6 ± 5.0.4% inhibition) and integrity (> 95 ± 2.3%), and the release of UV260 absorbing materials within 60 min (up to 3.2 fold increase, p < 0.01) of exposure. Further, SCL localized to the cytoplasm and hydrolyzed plasmid DNA. While in vitro checkerboard studies revealed that SCL potentiated the antimicrobial activity of topical antimicrobials such as polymixin, neomycin, and bacitracin (Fractional Inhibitory Concentration Index range, 0.26-0.37). Taken together these results suggest that SCL targets the membrane and DNA of MRSA to facilitate its anti-MRSA antimicrobial effect.

Overcoming Encouragement of Dragon Fruit Plant (Hylocereus undatus) against Stem Brown Spot Disease Caused by Neoscytalidium dimidiatum Using Bacillus subtilis Combined with Sodium Bicarbonate

  • Ratanaprom, Sanan;Nakkanong, Korakot;Nualsri, Charassri;Jiwanit, Palakrit;Rongsawat, Thanyakorn;Woraathakorn, Natthakorn
    • The Plant Pathology Journal
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    • 제37권3호
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    • pp.205-214
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    • 2021
  • The use of the supernatant from a Bacillus subtilis culture mixed with sodium bicarbonate was explored as a means of controlling stem brown spot disease in dragon fruit plants. In in vitro experiments, the B. subtilis supernatant used with sodium bicarbonate showed a strong inhibition effect on the growth of the fungus, Neoscytalidium dimidiatum, the agent causing stem brown spot disease and was notably effective in preventing fungal invasion of dragon fruit plant. This combination not only directly suppressed the growth of N. dimidiatum, but also indirectly affected the development of the disease by eliciting the dragon-fruit plant's defense response. Substantial levels of the pathogenesis-related proteins, chitinase and glucanase, and the phenylpropanoid biosynthetic pathway enzymes, peroxidase and phenyl alanine ammonia-lyase, were triggered. Significant lignin deposition was also detected in treated cladodes of injured dragon fruit plants in in vivo experiments. In summary, B. subtilis supernatant combined with sodium bicarbonate protected dragon fruit plant loss through stem brown spot disease during plant development in the field through pathogenic fungal inhibition and the induction of defense response mechanisms.

Variant of CHD1 gene resulting in a Korean case of Pilarowski-Bjornsson syndrome

  • Yoon Sunwoo;Soo Hyun Seo;Ho-Joong Kim;Moon Seok Park;Anna Cho
    • Journal of Genetic Medicine
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    • 제19권2호
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    • pp.111-114
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    • 2022
  • Many monogenic neurodevelopmental disorders have been newly identified in recent years owing to the rapid development of genetic sequencing technology. These include variants of the epigenetic machinery - up to 300 known epigenetic factors of which about 50 have been linked to specific clinical phenotypes. Chromodomain, helicase, DNA binding 1 (CHD1) is an ATP-dependent chromatin remodeler, known to be the causative gene of the autosomal dominant neurodevelopmental disorder Pilarowski-Bjornsson syndrome. Patients exhibit various degrees of global developmental delay, autism, speech apraxia, seizures, growth retardation, and craniofacial dysmorphism. We report the first case of Pilarowski-Bjornsson syndrome in Korea, due to a de novo missense variant of the CHD1 gene (c.862A>G, p.Thr288Ala) in a previously undiagnosed 17-year-old male. His infantile onset of severe global developmental delay, intellectual disability, speech apraxia, and failure to thrive are compatible with Pilarowski-Bjornsson syndrome. We also noted some features not previously reported in this syndrome such as skeletal dysplasia and ichthyosis. Further studies are needed to discover the specific phenotypes and pathogenic mechanisms behind this rare disorder.