• Title/Summary/Keyword: molecular mechanism

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Family of Hsp70 Molecular Chaperones and Their Regulators (Hsp70 분자 샤페론과 조절인자)

  • Chung, Kyung-Tae
    • Journal of Life Science
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    • v.17 no.12
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    • pp.1760-1765
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    • 2007
  • Proteins are involved in promoting or controlling virtually every event on which our lives depend. Proteins are synthesized in cytosol and in the endoplasmic reticulum where their synthesis machinery are tightly controlled. However, not all of newly synthesized proteins are survived and conduct their essential functions to maintain cell's lives. It was reported that one-third of synthesized proteins are rapidly destroyed by proteasome under the most physiological conditions. full-length translated proteins, which survived, must undergo proper folding and assemble process. Some proteins are spontaneously folded while others require molecular chaperones and folding enzymes to be properly folded. Molecular chaperones are ubiquitously present within the subcellular organelles and from bacteria to animals and plants. Among those members of Hsp70 family have been extensively studied and their regulators have been discovered in the last decade. Here, a brief overview is presented for functional mechanism of Hsp70 homologues and the roles of their regulators. Since biological function of Hsp70 family other than chaperonic function are expending the review would give basic understanding of partnership between Hsp70 family and their regulators.

Integrative applications of network pharmacology and molecular docking: An herbal formula ameliorates H9c2 cells injury through pyroptosis

  • Zhongwen Qi;Zhipeng Yan;Yueyao Wang;Nan Ji;Xiaoya Yang;Ao Zhang;Meng Li;Fengqin Xu;Junping Zhang
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.228-236
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    • 2023
  • Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 μM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1β levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.

Mechanism of guanine-specific DNA damage by UVA and its role in photocarcinogenesis and photoaging

  • Kawanishi, Shosuke;Oikawa, Shinji;Hiraku, Yusuke
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.150-153
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    • 2002
  • Solar UV light is a well-known carcinogen. UVA radiation is probably carcinogenic to humans. In addition, recent investigations point to the importance of UVA irradiation in the photoaging. We investigated the mechanism of sequence- specific DNA damage using $\^$32/P-Iabeled DNA fragments in relation to carcinogenesis and aging. Furthermore, we investigated whether UVA accelerates the telomere shortening in human WI-38 fibroblasts. The exposure of double- stranded DNA fragments to 365 nm light in the presence of endogenous sensitizers produced sequence-specific cleavage at the 5' site of 5'-GG-3' and 5'-GGG-3' sequences. In addition, HPLC analysis revealed that sensitizers plus 365 nm light increased the 8-oxodG content of double-stranded DNA. We discuss the mechanisms of guanine-specific DNA damagecaused by excited photosensitizers in relation to carcinogenesis and aging.

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Molecular Mechanism of Inflammatory Signaling and Predominant Role of Saposhnikovia divaricata as Anti-inflammatory Potential

  • Khan, Salman;Kim, Yeong Shik
    • Natural Product Sciences
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    • v.19 no.2
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    • pp.120-126
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    • 2013
  • Natural products have always been a pivotal source of new drug development. Dry roots of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a perennial herb and is also known as Bang Pung in traditional medicine. Numerous in vitro and in vivo studies have revealed the diverse pharmacological effects of S. divaricata and its role in the treatment of various diseases. This herb has exhibited significant inhibitory effects against inflammation and associated disorders. The present study explored the ethnopharmacological applications and molecular mechanisms behind the anti-inflammatory effects of S. divaricata herb and a single compound blockade of multi-signaling inflammatory cascades. Taken together, this review provides insight into the potential role of S. divaricata against various inflammatory diseases.

Epigallocatechin 3-gallate Binds to Human Salivary α-Amylase with Complex Hydrogen Bonding Interactions

  • Lee, Jee-Young;Jeong, Ki-Woong;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.32 no.7
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    • pp.2222-2226
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    • 2011
  • Amylase is a digestive enzyme that catalyses the starch into sugar. It has been reported that the green tea flavonoid (or polyphenols) (-)-epigallocatechin 3-gallate (EGCG) inhibits human salivary ${\alpha}$-amylase (HSA) and induced anti-nutritional effects. In this study, we performed docking study for seven EGCG-like flavonoids and HSA to understand the interaction mechanism of HSA and EGCG and suggest new possible flavonoid inhibitors of HSA. As a result, EGCG and (-)-epicatechin gallate (ECG) bind to HSA with complex hydrogen bonding interactions. These hydrogen bonding interactions are important for inhibitory activity of EGCG against HSA. We suggested that ECG can be a potent inhibitor of HSA. This study will be helpful to understand the mechanism of inhibition of HSA by EGCG and give insights to develop therapeutic strategies against diabetes.

Application of Pseudo Molecular Complexes (II). A New Mechanism for Aromatic Substitution (유사분자 착물의 응용 (제 2 보). 새로운 방향족 치환반응 기구)

  • Park Byung-Kak
    • Journal of the Korean Chemical Society
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    • v.19 no.3
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    • pp.179-185
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    • 1975
  • A new mechanism is proposed for aromatic substitution, involving the formation of pseudo molecular complexes at the transition state. It accounts for the addition reactions of aromatic compounds with double bond reagents such as ozone, somium tetraoxide and carbene as well as all of the features of electrophilic substitution reactions. The pseudo molecular complex has been proved to be formed by quantum-chemical considerations using the simple Huckel method.

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Ozone Deinking Mechanism of White Ledger (White ledger의 오존 탈묵 기구)

  • 원종명;노국일
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.33 no.3
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    • pp.24-28
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    • 2001
  • The utilization of wastepaper as a papermaking raw material is everlastingly required for the environmental protection of earth. However the recycling of wastepaper for this purpose cause another problem such as the increasing of the load of wastewater treatment, lower strength properties of paper, and poor printability, etc. The interest in the development of the environmentally friendly deinking technology is increased continuously. Thus, our research team have tried to apply the ozone to the deinking of white ledger and ONP, and obtained the positive results which can be considered as an alternative method for the conventional deinking method. The purpose of this study is to investigate the mechanism of ozone deinking. Styrene acrylate and polystyrene were treated with ozone and measured the change of molecular weight with the GPC. The molecular weight distribution obtained with GPC showed only slight increase by the ozone treatment, and gel formation by the polymerization was observed. Therefore the removal of ink particles with ozone treatment seems to be facilitated by the increase of the brittleness and decrease of adhesive property.

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MOLECULAR DYNAMICS SIMULATION OF THE INTERACTION BETWEEN CLUSTER BEAMS AND SOLID SURFACES

  • Kang, Hee-Jae;Lee, Min-Wha;Whang, Chung-Nam
    • Journal of the Korean Vacuum Society
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    • v.4 no.S2
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    • pp.139-147
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    • 1995
  • The mechanism of the ionized cluster beam deposition has been studied using Molecular Dynamics Simulation. The Embedded Atom Method(EAM) potential were used in the simulation. The impact of a Au95-cluster on Au(100) substrate was studied for the impact energies 0.15-10eV/atom. The dependency of the impact energy of cluster beam was observed. For the cluster energy impact of 10eV per atom, the defects on surface were created and the cluster embedded into substrate as an amorphous state. For the energy of 0.5eV per atom, the defect free homoepitaxial growth was observed and atomic scale nucleation was formated, which are in good agreement with experiment. Thus molecular dynamics simulation is very useful to study the mechanism of the ionized cluster beam deposition.

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Senotherapeutics and Their Molecular Mechanism for Improving Aging

  • Park, Jooho;Shin, Dong Wook
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.490-500
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    • 2022
  • Aging is defined as physiological dysfunction of the body and a key risk factor for human diseases. During the aging process, cellular senescence occurs in response to various extrinsic and intrinsic factors such as radiation-induced DNA damage, the activation of oncogenes, and oxidative stress. These senescent cells accumulate in many tissues and exhibit diverse phenotypes, such as resistance to apoptosis, production of senescence-associated secretory phenotype, cellular flattening, and cellular hypertrophy. They also induce abnormal dysfunction of the microenvironment and damage neighboring cells, eventually causing harmful effects in the development of various chronic diseases such as diabetes, cancer, and neurodegenerative diseases. Thus, pharmacological interventions targeting senescent cells, called senotherapeutics, have been extensively studied. These senotherapeutics provide a novel strategy for extending the health span and improving age-related diseases. In this review, we discuss the current progress in understanding the molecular mechanisms of senotherapeutics and provide insights for developing senotherapeutics.

Nystatin Drug as an Effective Corrosion Inhibitor for Mild Steel in Acidic Media- An Experimental and Theoretical Study

  • Mehmeti, Valbone
    • Corrosion Science and Technology
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    • v.21 no.1
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    • pp.21-31
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    • 2022
  • Potentiodynamic polarization, EIS measurements, quantum chemical calculations, and molecular dynamic simulations were used to investigate the corrosion behavior of mild steel in 0.5 M aqueous hydrochloric acid medium in the presence or absence of nystatin drug. Potentiodynamic tests suggested that this molecule could act as a mixed inhibitor due to its adsorption on the mild steel surface. The objective of this study was to exploit theoretical calculations to gain a better understanding mechanism of inhibition. Calculating the adsorption behavior of the investigated molecule on Fe (1 1 0) surface was accomplished using Monte Carlo simulation. Molecules were also investigated using Density Functional Theory (DFT), specifically PBE functional, in order to identify the link between molecular structure and corrosion inhibition behavior of the compound under investigation. Adsorption energies between nystatin and iron were estimated more accurately by utilizing Molecular Mechanics calculation with Periodic Boundary Conditions (PBC). Estimated theoretical parameters significantly assisted our understanding of the corrosion inhibition mechanism exhibited by this molecule. They were found to be in accord with experimental results.