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Article ; Online: In Vitro and In Vivo Model for Sepsis Through Non-canonical NLRP3 Inflammasome Activation.

Sun, Xiao / Kang, Tae-Bong / Lee, Kwang-Ho

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2459, Page(s) 137–147

Abstract: Sepsis is a complex disorder related to dysregulation of the host response to infection and is a major health problem worldwide owing to its high mortality rates. However, the exact mechanisms causing sepsis remains unclear because of the complexity of ... ...

Abstract	Sepsis is a complex disorder related to dysregulation of the host response to infection and is a major health problem worldwide owing to its high mortality rates. However, the exact mechanisms causing sepsis remains unclear because of the complexity of the underlying pathways. Dysregulation of non-canonical NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation induces septic shock by promoting pyroptosis and pro-inflammatory cytokine production (e.g., interleukin-1β) via caspase-11 and Gasdermin-D. Herein, we describe a rapid, simple method for evaluation of the degree of sepsis by investigating non-canonical inflammasome activation in both in vitro and in vivo models. The method is expected to be useful for testing and screening drugs for the treatment of sepsis.
MeSH term(s)	Caspases/metabolism ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Pyroptosis ; Sepsis
Chemical Substances	Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2144-8_14
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Article ; Online: The Molecular Links between Cell Death and Inflammasome.

Lee, Kwang-Ho / Kang, Tae-Bong

Cells

2019 Volume 8, Issue 9

Abstract: Programmed cell death pathways and inflammasome activation pathways can be genetically and functionally separated. Inflammasomes are specialized protein complexes that process pro-inflammatory cytokines, interleukin-1β (IL-1β), and IL-18 to bioactive ... ...

Abstract	Programmed cell death pathways and inflammasome activation pathways can be genetically and functionally separated. Inflammasomes are specialized protein complexes that process pro-inflammatory cytokines, interleukin-1β (IL-1β), and IL-18 to bioactive forms for protection from a wide range of pathogens, as well as environmental and host-derived danger molecules. Programmed cell death has been extensively studied, and its role in the development, homeostasis, and control of infection and danger is widely appreciated. Apoptosis and the recently recognized necroptosis are the best-characterized forms of programmed death, and the interplay between them through death receptor signaling is also being studied. Moreover, growing evidence suggests that many of the signaling molecules known to regulate programmed cell death can also modulate inflammasome activation in a cell-intrinsic manner. Therefore, in this review, we will discuss the current knowledge concerning the role of the signaling molecules originally associated with programmed cell death in the activation of inflammasome and IL-1β processing.
MeSH term(s)	Apoptosis/physiology ; Caspase 1/metabolism ; Caspase 8/metabolism ; Cell Death/immunology ; Cell Death/physiology ; Inflammasomes/immunology ; Inflammasomes/metabolism ; Interleukin-18/metabolism ; Macrophages/metabolism ; Necroptosis/physiology ; Protein Kinases/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Signal Transduction
Chemical Substances	Inflammasomes ; Interleukin-18 ; Protein Kinases (EC 2.7.-) ; Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Caspase 8 (EC 3.4.22.-) ; Caspase 1 (EC 3.4.22.36)
Language	English
Publishing date	2019-09-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells8091057
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Article ; Online: Programmed Cell Death in Immune Defense: Knowledge and Presumptions.

Wallach, David / Kang, Tae-Bong

Immunity

2018 Volume 49, Issue 1, Page(s) 19–32

Abstract: Cell-culture studies are our main source of knowledge of the various forms of programmed cell death. Yet genetic perturbations of death-protein function in animal models are almost the only source of our knowledge of the physiological roles of these ... ...

Abstract	Cell-culture studies are our main source of knowledge of the various forms of programmed cell death. Yet genetic perturbations of death-protein function in animal models are almost the only source of our knowledge of the physiological roles of these programs. Shortcomings in the state of knowledge acquired by these two experimental approaches are exemplified in this Perspective by reference to research on the contribution of apoptosis to lymphocyte development, a subject on which there is already much knowledge, and on the role of necroptosis in inflammation, about which information is just beginning to emerge. To address these shortcomings, there is need to find ways to verify the notions obtained through the current experimental approaches by directly monitoring death programs within specific cells in vivo.
MeSH term(s)	Animals ; Apoptosis/immunology ; Cell Death ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Lymphocytes/immunology ; Lymphocytes/pathology ; Models, Biological ; Necrosis/immunology ; Signal Transduction/immunology
Language	English
Publishing date	2018-08-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2018.06.019
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Article ; Online: Regulation of Caspase-8 Activity at the Crossroads of Pro-Inflammation and Anti-Inflammation.

Han, Jun-Hyuk / Park, Jooho / Kang, Tae-Bong / Lee, Kwang-Ho

International journal of molecular sciences

2021 Volume 22, Issue 7

Abstract: Caspase-8 has been classified as an apoptotic caspase, and its initial definition was an initiator of extrinsic cell death. During the past decade, the concept of caspase-8 functioning has been changed by findings of its additional roles in diverse ... ...

Abstract	Caspase-8 has been classified as an apoptotic caspase, and its initial definition was an initiator of extrinsic cell death. During the past decade, the concept of caspase-8 functioning has been changed by findings of its additional roles in diverse biological processes. Although caspase-8 was not originally thought to be involved in the inflammation process, many recent works have determined that caspase-8 plays an important role in the regulatory functions of inflammatory processes. In this review, we describe the recent advances in knowledge regarding the manner in which caspase-8 modulates the inflammatory responses concerning inflammasome activation, cell death, and cytokine induction.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Apoptosis ; Caspase 8/metabolism ; Cell Death ; Cytokines/metabolism ; Humans ; Inflammasomes/metabolism ; Inflammation ; Interleukin-1beta/metabolism ; Mice ; NF-kappa B/metabolism ; Necroptosis ; Pyroptosis
Chemical Substances	Anti-Inflammatory Agents ; Cytokines ; Inflammasomes ; Interleukin-1beta ; NF-kappa B ; CASP8 protein, human (EC 3.4.22.-) ; Casp8 protein, mouse (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-)
Language	English
Publishing date	2021-03-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22073318
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Article ; Online: Cornus officinalis

Lee, Se-Bin / Kang, Ju-Hui / Sim, Eun-Jung / Jung, Ye-Rin / Kim, Jeong-Hyeon / Hillman, Prima F / Nam, Sang-Jip / Kang, Tae-Bong

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been ... ...

Abstract	The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of
MeSH term(s)	Humans ; Inflammasomes/metabolism ; Imiquimod/adverse effects ; Cornus ; HEK293 Cells ; Psoriasis/chemically induced ; Psoriasis/drug therapy ; Dermatitis ; Inflammation ; Plant Extracts/adverse effects ; Seeds/metabolism ; Caspases ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Interleukin-1beta/metabolism ; Caspase 1/metabolism ; DNA-Binding Proteins/metabolism
Chemical Substances	Inflammasomes ; Imiquimod (P1QW714R7M) ; Plant Extracts ; Caspases (EC 3.4.22.-) ; NLR Family, Pyrin Domain-Containing 3 Protein ; Interleukin-1beta ; Caspase 1 (EC 3.4.22.36) ; AIM2 protein, human ; DNA-Binding Proteins
Language	English
Publishing date	2023-03-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065653
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Article: Development of a Peptide-Based Nano-Sized Cathepsin B Inhibitor for Anticancer Therapy.

Park, So-Hyeon / Lee, Jun-Hyuck / Yang, Seong-Bin / Lee, Dong-Nyeong / Kang, Tae-Bong / Park, Jooho

Pharmaceutics

2023 Volume 15, Issue 4

Abstract: Numerous cathepsin B inhibitors have been developed and are under investigation as potential cancer treatments. They have been evaluated for their ability to inhibit cathepsin B activity and reduce tumor growth. However, they have shown critical ... ...

Abstract	Numerous cathepsin B inhibitors have been developed and are under investigation as potential cancer treatments. They have been evaluated for their ability to inhibit cathepsin B activity and reduce tumor growth. However, they have shown critical limitations, including low anticancer efficacy and high toxicity, due to their low selectivity and delivery problems. In this study, we developed a novel peptide and drug conjugate (PDC)-based cathepsin B inhibitor using cathepsin-B-specific peptide (RR) and bile acid (BA). Interestingly, this RR and BA conjugate (RR-BA) was able to self-assemble in an aqueous solution, and as a result, it formed stable nanoparticles. The nano-sized RR-BA conjugate showed significant cathepsin B inhibitory effects and anticancer effects against mouse colorectal cancer (CT26) cells. Its therapeutic effect and low toxicity were also confirmed in CT26 tumor-bearing mice after intravenous injection. Therefore, based on these results, the RR-BA conjugate could be developed as an effective anticancer drug candidate for inhibiting cathepsin B in anticancer therapy.
Language	English
Publishing date	2023-04-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15041131
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Article ; Online: Doxorubicin covalently conjugated heparin displays anti-cancer activity as a self-assembled nanoparticle with a low-anticoagulant effect

Lee, Jae-Hyeon / Yang, Seong-Bin / Lee, Jun-Hyuck / Lim, Hansol / Lee, Seokwoo / Kang, Tae-bong / Lim, Ji-Hong / Kim, Yŏng-jun / Park, Jooho

Carbohydrate Polymers. 2023 Apr. 18, p.120930-

2023 , Page(s) 120930–

Abstract: Heparin is a glycosaminoglycans (GAGs) member and well-known FDA-approved anticoagulant that has been widely used in the clinic for 100 years. It has also been evaluated in various fields for further clinical applications, such as in anti-cancer or anti- ... ...

Abstract	Heparin is a glycosaminoglycans (GAGs) member and well-known FDA-approved anticoagulant that has been widely used in the clinic for 100 years. It has also been evaluated in various fields for further clinical applications, such as in anti-cancer or anti-inflammatory therapy beyond its anticoagulant effect. Here, we sought to utilize heparin molecules as drug carriers by directly conjugating the anticancer drug doxorubicin to the carboxyl group of unfractionated heparin. Given the molecular action of doxorubicin in intercalating DNA, it is expected to be less effective when structurally combined with other molecules. However, by utilizing doxorubicin molecules to produce reactive oxygen species (ROS), we found that the heparin–doxorubicin conjugates have significant cytotoxic ability to kill CT26 tumor cells with low anticoagulant activity. Several doxorubicin molecules were bound to heparin to provide sufficient cytotoxic capability and self-assembly ability due to their amphiphilic properties. The self-assembled formation of these nanoparticles was demonstrated through DLS, SEM and TEM. The cytotoxic ROS-generating doxorubicin-conjugated heparins could inhibit tumor growth and metastasis in CT26-bearing Balb/c animal models. Our results demonstrate that this cytotoxic doxorubicin-based heparin conjugate can significantly inhibit tumor growth and metastasis, thus showing promise as a potential new anti-cancer therapeutic.
Keywords	DNA ; animals ; anticoagulant activity ; anticoagulants ; antineoplastic activity ; cancer therapy ; chemical bonding ; cytotoxicity ; doxorubicin ; heparin ; metastasis ; nanoparticles ; neoplasms ; reactive oxygen species ; Polysaccharide ; Unfractionated heparin ; Bioconjugate ; Self-assembly ; Apoptosis
Language	English
Dates of publication	2023-0418
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	1501516-6
ISSN	1879-1344 ; 0144-8617
ISSN (online)	1879-1344
ISSN	0144-8617
DOI	10.1016/j.carbpol.2023.120930
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Molecular Targeting of VEGF with a Suramin Fragment-DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins.

Park, Jooho / Kang, Tae-Bong / Lim, Ji-Hong / Won, Hyung-Sik

Biomolecules

2020 Volume 11, Issue 1

Abstract: Molecular targeting of growth factors has shown great therapeutic potential in pharmaceutical research due to their roles in pathological conditions. In the present study, we developed a novel suramin fragment and deoxycholic acid conjugate (SFD) that ... ...

Abstract	Molecular targeting of growth factors has shown great therapeutic potential in pharmaceutical research due to their roles in pathological conditions. In the present study, we developed a novel suramin fragment and deoxycholic acid conjugate (SFD) that exhibited the potential to bind to the heparin-binding site (HBD) of vascular endothelial growth factor (VEGF) and to inhibit its pathogenic action for the first time. Notably, SFD was optimally designed for binding to the HBD of VEGF using the naphthalenetrisulfonate group, allowing to observe its excellent binding efficacy in a surface plasmon resonance (SPR) study, showing remarkable binding affinity (K
MeSH term(s)	Binding Sites/drug effects ; Desoxycorticosterone Acetate/chemistry ; Desoxycorticosterone Acetate/pharmacology ; Heparin/chemistry ; Heparin/pharmacology ; Human Umbilical Vein Endothelial Cells ; Humans ; Suramin/chemistry ; Suramin/pharmacology ; Surface Plasmon Resonance ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Suramin (6032D45BEM) ; Desoxycorticosterone Acetate (6E0A168OB8) ; Heparin (9005-49-6)
Language	English
Publishing date	2020-12-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11010046
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Article ; Online: NLRP3 Ubiquitination-A New Approach to Target NLRP3 Inflammasome Activation.

Akther, Mahbuba / Haque, Md Ezazul / Park, Jooho / Kang, Tae-Bong / Lee, Kwang-Ho

International journal of molecular sciences

2021 Volume 22, Issue 16

Abstract: In response to diverse pathogenic and danger signals, the cytosolic activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing (3)) inflammasome complex is a critical event in the maturation and release of some inflammatory cytokines in the state ... ...

Abstract	In response to diverse pathogenic and danger signals, the cytosolic activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing (3)) inflammasome complex is a critical event in the maturation and release of some inflammatory cytokines in the state of an inflammatory response. After activation of the NLRP3 inflammasome, a series of cellular events occurs, including caspase 1-mediated proteolytic cleavage and maturation of the IL-1β and IL-18, followed by pyroptotic cell death. Therefore, the NLRP3 inflammasome has become a prime target for the resolution of many inflammatory disorders. Since NLRP3 inflammasome activation can be triggered by a wide range of stimuli and the activation process occurs in a complex, it is difficult to target the NLRP3 inflammasome. During the activation process, various post-translational modifications (PTM) of the NLRP3 protein are required to form a complex with other components. The regulation of ubiquitination and deubiquitination of NLRP3 has emerged as a potential therapeutic target for NLRP3 inflammasome-associated inflammatory disorders. In this review, we discuss the ubiquitination and deubiquitination system for NLRP3 inflammasome activation and the inhibitors that can be used as potential therapeutic agents to modulate the activation of the NLRP3 inflammasome.
MeSH term(s)	Cytosol/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Inflammasomes/metabolism ; Molecular Targeted Therapy ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Ubiquitination/drug effects
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human
Language	English
Publishing date	2021-08-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22168780
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Article ; Online: Heparin and Its Derivatives: Challenges and Advances in Therapeutic Biomolecules.

Banik, Nipa / Yang, Seong-Bin / Kang, Tae-Bong / Lim, Ji-Hong / Park, Jooho

International journal of molecular sciences

2021 Volume 22, Issue 19

Abstract: Heparin has been extensively studied as a safe medicine and biomolecule over the past few decades. Heparin derivatives, including low-molecular-weight heparins (LMWH) and heparin pentasaccharide, are effective anticoagulants currently used in clinical ... ...

Abstract	Heparin has been extensively studied as a safe medicine and biomolecule over the past few decades. Heparin derivatives, including low-molecular-weight heparins (LMWH) and heparin pentasaccharide, are effective anticoagulants currently used in clinical settings. They have also been studied as functional biomolecules or biomaterials for various therapeutic uses to treat diseases. Heparin, which has a similar molecular structure to heparan sulfate, can be used as a remarkable biomedicine due to its uniquely high safety and biocompatibility. In particular, it has recently drawn attention for use in drug-delivery systems, biomaterial-based tissue engineering, nanoformulations, and new drug-development systems through molecular formulas. A variety of new heparin-based biomolecules and conjugates have been developed in recent years and are currently being evaluated for use in clinical applications. This article reviews heparin derivatives recently studied in the field of drug development for the treatment of various diseases.
MeSH term(s)	Anticoagulants/chemistry ; Anticoagulants/therapeutic use ; Biocompatible Materials/chemistry ; Biocompatible Materials/therapeutic use ; Drug Delivery Systems ; Heparin, Low-Molecular-Weight/chemistry ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Tissue Engineering
Chemical Substances	Anticoagulants ; Biocompatible Materials ; Heparin, Low-Molecular-Weight
Language	English
Publishing date	2021-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms221910524
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