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Article: Omarigliptin Mitigates 6-Hydroxydopamine- or Rotenone-Induced Oxidative Toxicity in PC12 Cells by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Actions.

Gouda, Noha A / Cho, Jungsook

2022 Volume 11, Issue 10

Abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors are reported to exhibit promising effects on several pathological processes associated with Parkinson's disease (PD). To explore its repositioning potential as an antiparkinsonian agent, we evaluated the effects ... ...

Abstract	Dipeptidyl peptidase-4 (DPP-4) inhibitors are reported to exhibit promising effects on several pathological processes associated with Parkinson's disease (PD). To explore its repositioning potential as an antiparkinsonian agent, we evaluated the effects of omarigliptin (OMG), a DPP-4 inhibitor recently approved as a hypoglycemic drug, on neurotoxin-induced toxicity, using PC12 cells as a cellular model of PD. The molecular mechanism(s) underlying its protective activity was also investigated. OMG alleviated oxidative toxicity and the production of reactive oxygen species induced by 6-hydroxydopamine (6-OHDA) or rotenone. It also partially attenuated the formation of DPPH radicals and lipid peroxidation, demonstrating the antioxidant properties of OMG. OMG upregulated Nrf2 and heme oxygenase-1 (HO-1). Notably, treatment with a selective HO-1 inhibitor and Nrf2 knockdown by siRNA abolished the beneficial effects of OMG, indicating that the activated Nrf2/HO-1 signaling was responsible for the protective activity. Moreover, OMG exhibited anti-inflammatory activity, blocking inflammatory molecules, such as nitric oxide (NO) and inducible NO synthase, through inhibition of IκBα phosphorylation and NF-κB activation in an Akt-dependent fashion. Finally, OMG decreased the levels of cleaved caspase-3 and Bax and increased the level of Bcl-2, indicating its anti-apoptotic properties. Collectively, these results demonstrate that OMG alleviates the neurotoxin-induced oxidative toxicity through Nrf2/HO-1-mediated antioxidant, NF-κB-mediated anti-inflammatory, and anti-apoptotic mechanisms in PC12 cells. Our findings elucidating multiple mechanisms of antiparkinsonian activity strongly support the therapeutic potential of OMG in the treatment of PD.
Language	English
Publishing date	2022-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox11101940
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Article ; Online: Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance.

Nguyen, Ngoc Minh / Cho, Jungsook

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Hedgehog (Hh) signaling is a highly conserved pathway that plays a vital role during embryonic development. Recently, uncontrolled activation of this pathway has been demonstrated in various types of cancer. Therefore, Hh pathway inhibitors have emerged ... ...

Abstract	Hedgehog (Hh) signaling is a highly conserved pathway that plays a vital role during embryonic development. Recently, uncontrolled activation of this pathway has been demonstrated in various types of cancer. Therefore, Hh pathway inhibitors have emerged as an important class of anti-cancer agents. Unfortunately, however, their reputation has been tarnished by the emergence of resistance during therapy, necessitating clarification of mechanisms underlying the drug resistance. In this review, we briefly overview canonical and non-canonical Hh pathways and their inhibitors as targeted cancer therapy. In addition, we summarize the mechanisms of resistance to Smoothened (SMO) inhibitors, including point mutations of the drug binding pocket or downstream molecules of SMO, and non-canonical mechanisms to reinforce Hh pathway output. A distinct mechanism involving loss of primary cilia is also described to maintain GLI activity in resistant tumors. Finally, we address the main strategies to circumvent the drug resistance. These strategies include the development of novel and potent inhibitors targeting different components of the canonical Hh pathway or signaling molecules of the non-canonical pathway. Further studies are necessary to avoid emerging resistance to Hh inhibitors and establish an optimal customized regimen with improved therapeutic efficacy to treat various types of cancer, including basal cell carcinoma.
MeSH term(s)	Animals ; Clinical Trials as Topic ; Drug Resistance, Neoplasm ; Hedgehog Proteins/metabolism ; Humans ; Models, Biological ; Molecular Targeted Therapy ; Signal Transduction
Chemical Substances	Hedgehog Proteins
Language	English
Publishing date	2022-02-03
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/ijms23031733
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Article ; Online: Gut Microbiota and Alzheimer's Disease: How to Study and Apply Their Relationship.

Nguyen, Ngoc Minh / Cho, Jungsook / Lee, Choongho

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Gut microbiota (GM), the microorganisms in the gastrointestinal tract, contribute to the regulation of brain homeostasis through bidirectional communication between the gut and the brain. GM disturbance has been discovered to be related to various ... ...

Abstract	Gut microbiota (GM), the microorganisms in the gastrointestinal tract, contribute to the regulation of brain homeostasis through bidirectional communication between the gut and the brain. GM disturbance has been discovered to be related to various neurological disorders, including Alzheimer's disease (AD). Recently, the microbiota-gut-brain axis (MGBA) has emerged as an enticing subject not only to understand AD pathology but also to provide novel therapeutic strategies for AD. In this review, the general concept of the MGBA and its impacts on the development and progression of AD are described. Then, diverse experimental approaches for studying the roles of GM in AD pathogenesis are presented. Finally, the MGBA-based therapeutic strategies for AD are discussed. This review provides concise guidance for those who wish to obtain a conceptual and methodological understanding of the GM and AD relationship with an emphasis on its practical application.
MeSH term(s)	Humans ; Alzheimer Disease/therapy ; Gastrointestinal Microbiome/physiology ; Brain ; Brain-Gut Axis
Chemical Substances	methylglyoxal bis(3-aminopropylamidinohydrazone) (121496-63-7)
Language	English
Publishing date	2023-02-17
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/ijms24044047
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Article ; Online: Pathophysiological Roles of Histamine Receptors in Cancer Progression: Implications and Perspectives as Potential Molecular Targets.

Nguyen, Phuong Linh / Cho, Jungsook

Biomolecules

2021 Volume 11, Issue 8

Abstract: High levels of histamine and histamine receptors (HRs), including H1R~H4R, are found in many different types of tumor cells and cells in the tumor microenvironment, suggesting their involvement in tumor progression. This review summarizes the latest ... ...

Abstract	High levels of histamine and histamine receptors (HRs), including H1R~H4R, are found in many different types of tumor cells and cells in the tumor microenvironment, suggesting their involvement in tumor progression. This review summarizes the latest evidence demonstrating the pathophysiological roles of histamine and its cognate receptors in cancer biology. We also discuss the novel therapeutic approaches of selective HR ligands and their potential prognostic values in cancer treatment. Briefly, histamine is highly implicated in cancer development, growth, and metastasis through interactions with distinct HRs. It also regulates the infiltration of immune cells into the tumor sites, exerting an immunomodulatory function. Moreover, the effects of various HR ligands, including H1R antagonists, H2R antagonists, and H4R agonists, on tumor progression in many different cancer types are described. Interestingly, the expression levels of HR subtypes may serve as prognostic biomarkers in several cancers. Taken together, HRs are promising targets for cancer treatment, and HR ligands may offer novel therapeutic potential, alone or in combination with conventional therapy. However, due to the complexity of the pathophysiological roles of histamine and HRs in cancer biology, further studies are warranted before HR ligands can be introduced into clinical settings.
MeSH term(s)	Animals ; Disease Progression ; Histamine/metabolism ; Humans ; Immune System ; Ligands ; Mast Cells/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; Prognosis ; Receptors, Histamine/metabolism ; Receptors, Histamine H3/metabolism ; Receptors, Histamine H4/metabolism ; Signal Transduction ; T-Lymphocytes/cytology ; Tumor Microenvironment
Chemical Substances	Ligands ; Receptors, Histamine ; Receptors, Histamine H3 ; Receptors, Histamine H4 ; Histamine (820484N8I3)
Language	English
Publishing date	2021-08-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11081232
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Article: Emerging Therapeutic Strategies for Parkinson's Disease and Future Prospects: A 2021 Update.

Gouda, Noha A / Elkamhawy, Ahmed / Cho, Jungsook

Biomedicines

2022 Volume 10, Issue 2

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder pathologically distinguished by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Muscle rigidity, tremor, and bradykinesia are all clinical motor hallmarks of PD. Several ...

Abstract	Parkinson's disease (PD) is a neurodegenerative disorder pathologically distinguished by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Muscle rigidity, tremor, and bradykinesia are all clinical motor hallmarks of PD. Several pathways have been implicated in PD etiology, including mitochondrial dysfunction, impaired protein clearance, and neuroinflammation, but how these factors interact remains incompletely understood. Although many breakthroughs in PD therapy have been accomplished, there is currently no cure for PD, only trials to alleviate the related motor symptoms. To reduce or stop the clinical progression and mobility impairment, a disease-modifying approach that can directly target the etiology rather than offering symptomatic alleviation remains a major unmet clinical need in the management of PD. In this review, we briefly introduce current treatments and pathophysiology of PD. In addition, we address the novel innovative therapeutic targets for PD therapy, including α-synuclein, autophagy, neurodegeneration, neuroinflammation, and others. Several immunomodulatory approaches and stem cell research currently in clinical trials with PD patients are also discussed. Moreover, preclinical studies and clinical trials evaluating the efficacy of novel and repurposed therapeutic agents and their pragmatic applications with encouraging outcomes are summarized. Finally, molecular biomarkers under active investigation are presented as potentially valuable tools for early PD diagnosis.
Language	English
Publishing date	2022-02-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10020371
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Article ; Online: Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer's Disease, Parkinson's Disease, and Depression with Pharmacokinetic and Safety Profiles.

Do, Ha Thi Thu / Cho, Jungsook

International journal of molecular sciences

2020 Volume 21, Issue 17

Abstract: Alzheimer's disease (AD), Parkinson's disease (PD), and depression are growing burdens for society globally, partly due to a lack of effective treatments. Mangosteen ( ...

Abstract	Alzheimer's disease (AD), Parkinson's disease (PD), and depression are growing burdens for society globally, partly due to a lack of effective treatments. Mangosteen (
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Amines/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Depression/drug therapy ; Depression/metabolism ; Garcinia mangostana/chemistry ; Humans ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/metabolism ; Parkinson Disease/drug therapy ; Parkinson Disease/metabolism ; Plant Extracts/chemistry ; Xanthones/chemistry ; Xanthones/pharmacokinetics ; Xanthones/therapeutic use ; alpha-Synuclein/metabolism
Chemical Substances	Amines ; Amyloid beta-Peptides ; Plant Extracts ; Xanthones ; alpha-Synuclein
Language	English
Publishing date	2020-08-27
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/ijms21176211
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Article ; Online: Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells.

Do, Ha Thi Thu / Cho, Jungsook

International journal of molecular sciences

2020 Volume 22, Issue 1

Abstract: Chemokine-receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration ... ...

Abstract	Chemokine-receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER
MeSH term(s)	A549 Cells ; Breast Neoplasms/metabolism ; Cell Movement ; Chemokines, C/metabolism ; Epithelial-Mesenchymal Transition ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction
Chemical Substances	Chemokines, C ; HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit ; Receptors, G-Protein-Coupled ; XCL1 protein, human ; XCR1 protein, human ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2020-12-23
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/ijms22010089
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Article: Induction of Paraptotic Cell Death in Breast Cancer Cells by a Novel Pyrazolo[3,4-

Nguyen, Phuong Linh / Lee, Chang Hoon / Lee, Heesoon / Cho, Jungsook

Antioxidants (Basel, Switzerland)

2022 Volume 11, Issue 1

Abstract: Chemotherapy has been a standard intervention for a variety of cancers to impede tumor growth, mainly by inducing apoptosis. However, development of resistance to this regimen has led to a growing interest and demand for drugs targeting alternative cell ... ...

Abstract	Chemotherapy has been a standard intervention for a variety of cancers to impede tumor growth, mainly by inducing apoptosis. However, development of resistance to this regimen has led to a growing interest and demand for drugs targeting alternative cell death modes, such as paraptosis. Here, we designed and synthesized a novel derivative of a pyrazolo[3,4-
Language	English
Publishing date	2022-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox11010117
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Article: Anxiolytic effect of Korean Red Ginseng through upregulation of serotonin and GABA transmission and BDNF expression in immobilized mice.

Bui, Bich Phuong / Nguyen, Phuong Linh / Do, Ha Thi Thu / Cho, Jungsook

Journal of ginseng research

2022 Volume 46, Issue 6, Page(s) 819–829

Abstract: Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like ... ...

Abstract	Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.
Language	English
Publishing date	2022-08-05
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2765273-7
ISSN	2093-4947 ; 1226-8453
ISSN (online)	2093-4947
ISSN	1226-8453
DOI	10.1016/j.jgr.2022.07.007
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Article: Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain.

Bui, Bich Phuong / Nguyen, Phuong Linh / Lee, Kyeong / Cho, Jungsook

Cancers

2022 Volume 14, Issue 24

Abstract: Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the transcription of many genes that are responsible for the adaptation and survival of tumor cells in hypoxic environments. Over the past few decades, tremendous efforts ... ...

Abstract	Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the transcription of many genes that are responsible for the adaptation and survival of tumor cells in hypoxic environments. Over the past few decades, tremendous efforts have been made to comprehensively understand the role of HIF-1 in tumor progression. Based on the pivotal roles of HIF-1 in tumor biology, many HIF-1 inhibitors interrupting expression, stabilization, DNA binding properties, or transcriptional activity have been identified as potential therapeutic agents for various cancers, yet none of these inhibitors have yet been successfully translated into clinically available cancer treatments. In this review, we briefly introduce the regulation of the HIF-1 pathway and summarize its roles in tumor cell proliferation, angiogenesis, and metastasis. In addition, we explore the implications of HIF-1 in the development of drug resistance and cancer-related pain: the most commonly encountered obstacles during conventional anticancer therapies. Finally, the current status of HIF-1 inhibitors in clinical trials and their perspectives are highlighted, along with their modes of action. This review provides new insights into novel anticancer drug development targeting HIF-1. HIF-1 inhibitors may be promising combinational therapeutic interventions to improve the efficacy of current cancer treatments and reduce drug resistance and cancer-related pain.
Language	English
Publishing date	2022-12-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14246054
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