Conferring liver selectivity to a thyromimetic using a novel nanoparticle increases therapeutic efficacy in a diet-induced obesity animal model

Wu, Ruiling; Prachyathipsakul, Theeraphop; Zhuang, Jiaming; Liu, Hongxu; Han, Yanhui; Liu, Bin; Gong, Shuai; Qiu, Jingyi; Wong, Siu; Ribbe, Alexander; Medeiros, Jewel; Bhagabati, Jayashree; Gao, Jingjing; Wu, Peidong; Dutta, Ranit; Herrera, Roman; Faraci, Steve; Xiao, Hang; Thayumanavan, S

doi:10.1093/pnasnexus/pgad252

Cited by 4 publications

(1 citation statement)

References 55 publications

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“…Studies have sought to use maternal diets as an intervention for altered immunological programming and neural defects in offspring [ 217 ]. Will it be possible in the future to introduce targeted genetically modified immune cells as therapy for metabolically rewiring the immune system [ 218 , 219 ]? Given the increasing numbers of children and adolescents suffering from metabolic and behavioral disorders, and the role that inflammation may play in triggering the origins of disease, understanding the relationship between poor maternal diets and developmental programming of the immune system during early life may play a crucial role in maintaining the delicate balance between health and disease in the 21st century.…”

Section: Discussionmentioning

confidence: 99%

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

Nelson,

Friedman

2024

IJMS

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Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

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Section: Discussionmentioning

confidence: 99%

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

Nelson,

Friedman

2024

IJMS

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Drug‐Loaded Nanogel for Efficient Orchestration of Cell Death Pathways by Intramitochondrial Disulfide Polymerization

Choi,

Kim,

Kim

et al. 2023

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Chemotherapy using a nanoscaled drug delivery system is an effective cancer therapy, but its high drug concentration often causes drug resistance in cancer cells and normal cell damage. Combination therapy involving two or more different cell signaling pathways can be a powerful tool to overcome the limitations of chemotherapy. Herein, this article presents nanogel (NG)‐mediated co‐delivery of a chemodrug camptothecin (CPT) and mitochondria‐targeting monomer (MT monomer) for efficient activation of two modes of the programmed cell death pathway (apoptosis and necroptosis) and synergistic enhancement of cancer therapy. CPT and the monomer are incorporated together into the redox‐degradable polymeric NGs for release in response to the intracellular glutathione. The MT monomer is shown to undergo reactive oxygen species (ROS)‐triggered disulfide polymerization inside the cancerous mitochondria in cooperation with the chemotherapeutic CPT elevating the intracellular ROS level. The CPT/monomer interconnection in cell death mechanisms for mitochondrial dysfunction and enhanced cell death is evidenced by a series of cell analyses showing ROS generation, mitochondria damage, impacts on (non)cancerous or drug‐resistant cells, and cell death modes. The presented work provides beneficial insights for utilizing combination therapy to facilitate a desired cell death mechanism and developing a novel nanosystem for more efficacious cancer treatment.

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Actions of thyroid hormones and thyromimetics on the liver

Sinha,

Bruinstroop,

Yen

2024

Nat Rev Gastroenterol Hepatol

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Conferring liver selectivity to a thyromimetic using a novel nanoparticle increases therapeutic efficacy in a diet-induced obesity animal model

Cited by 4 publications

References 55 publications

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

Drug‐Loaded Nanogel for Efficient Orchestration of Cell Death Pathways by Intramitochondrial Disulfide Polymerization

Actions of thyroid hormones and thyromimetics on the liver

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