Polymeric micelles coated with hybrid nanovesicles enhance the therapeutic potential of the reversible topoisomerase inhibitor camptothecin in a mouse model

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Several treatments for PD have focused on the management of physical symptoms using dopaminergic agents. However, these treatments induce various adverse effects, including hallucinations and cognitive impairment, owing to non-targeted brain delivery, while alleviating motor symptoms. Furthermore, these therapies are not considered ultimate cures owing to limited brain self-repair and regeneration abilities. In the present study, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASCs) using magnetic nanoparticles in a 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We used the Maestro imaging system and magnetic resonance imaging (MRI) for in vivo tracking after transplantation of magnetic nanoparticle-loaded hASCs to the PD mouse model. The Maestro imaging system revealed strong hASCs signals in the brains of PD model mice. In particular, MRI revealed hASCs distribution in the substantia nigra of hASCs-injected PD mice. Behavioral evaluations, including apomorphine-induced rotation and rotarod performance, were significantly recovered in hASCs-injected 6-OHDA induced PD mice when compared with saline-treated counterparts. Herein, we investigated whether hASCs transplantation using magnetic nanoparticles recovered motor functions through targeted brain distribution in a 6-OHDA induced PD mice. These results indicate that magnetic nanoparticle-based hASCs transplantation could be a potential therapeutic strategy in PD.

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miR-19a/19b improves the therapeutic potential of mesenchymal stem cells in a mouse model of myocardial infarction

Gene Therapy ◽

10.1038/s41434-020-0122-3 ◽

2020 ◽

Cited By ~ 3

Author(s):

Chengbo Chen ◽

Tianbao Chen ◽

Yangyi Li ◽

Youbang Xu

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mouse Model ◽

Therapeutic Potential

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MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500622 ◽

2016 ◽

Vol 44 (06) ◽

pp. 1111-1125 ◽

Cited By ~ 10

Author(s):

Muhammad Jahangir Hossen ◽

Mi-Yeon Kim ◽

Jae Youl Cho

Keyword(s):

Mouse Model ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Elevated Serum ◽

Human Monocyte ◽

Serum Levels ◽

Mitogen Activated Protein Kinase ◽

Xanthium Strumarium ◽

U937 Cells ◽

Anti Inflammatory

Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

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Therapeutic potential of cell-type selective optogenetics for a mouse model with urinary frequency

European Urology ◽

10.1016/s0302-2838(21)00406-1 ◽

2021 ◽

Vol 79 ◽

pp. S15

Author(s):

H. Shimura ◽

S. Manita ◽

T. Mochizuki ◽

Y. Matsuda ◽

T. Ihara ◽

...

Keyword(s):

Mouse Model ◽

Therapeutic Potential ◽

Cell Type ◽

Urinary Frequency

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Phyto-therapeutic potential of stem bark of the wonder tree, Prosopis cineraria (L.) Druce in LPS-induced mouse model: An Anti-Inflammatory Study

Clinical Phytoscience ◽

10.1186/s40816-020-00168-x ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Veena Sharma ◽

Preeti Sharma

Keyword(s):

Mouse Model ◽

Therapeutic Potential ◽

Stem Bark ◽

Prosopis Cineraria ◽

Anti Inflammatory

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GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness

Blood ◽

10.1182/blood.2020008948 ◽

2021 ◽

Author(s):

Julie Agopian ◽

Quentin Da Costa ◽

Quang Vo Nguyen ◽

Giulia Scorrano ◽

Paraskevi Kousteridou ◽

...

Keyword(s):

Mouse Model ◽

Tyrosine Kinases ◽

Inflammatory Responses ◽

Immunoglobulin E ◽

Therapeutic Potential ◽

Systemic Mastocytosis ◽

High Plasma ◽

Humanized Mouse Model ◽

Acute Response ◽

Genes Encoding

Systemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Here, we show that plasma metabolomic profiles were able to discriminate indolent from advanced forms of the disease. We identified N-acetyl-D-glucosamine (GlcNAc) as the most predictive metabolite of SM severity. High plasma levels of GlcNAc in patients with advanced SM correlated with the activation of the GlcNAc-fed hexosamine biosynthesis pathway (HBP) in patients BM aspirates and purified BM MCs. At the functional level, GlcNAc enhanced human neoplastic MCs proliferation and promoted rapid health deterioration in a humanized mouse model of SM. In addition, in the presence of GlcNAc, immunoglobulin E-stimulated MCs triggered enhanced release of proinflammatory cytokines and a stronger acute response in a mouse model of passive cutaneous anaphylaxis. Mechanistically, elevated GlcNAc levels promoted the transcriptional accessibility of chromatin regions that contain genes encoding mediators of receptor tyrosine kinases cascades and inflammatory responses, thus leading to a more aggressive phenotype. Therefore, GlcNAc is an oncometabolite driver of SM aggressiveness. This study suggests the therapeutic potential for targeting metabolic pathways in MC-related diseases to manipulate MCs effector functions.

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