Marc A. Giulianotti

Biomanufacturing in low Earth orbit: A paradigm shift

Davide Marotta, Steven R. Bauer, Joshua Hunsberger, Jana Stoudemire et autres

This perspective article explores the transformative potential of biomanufacturing in low Earth orbit (LEO) for regenerative medicine. Building on key symposia and workshops, it highlights the International Space Station (ISS) National Laboratory's role in advancing tissue engineering through microgravity research. The article …

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Novel Lipophagy Inducers as Potential Therapeutics for Lipid Metabolism Disorders

Rachel Njeim, Bassel Awada, Haley M. Donow, Haley Gye et autres

Dysregulation of lipid homeostasis is associated with a wide range of pathologies encompassing neurological, metabolic, cardiovascular, oncological, and renal disorders. We previously showed that lipid droplet (LD) accumulation in podocytes contributes to the progression of diabetic kidney disease (DKD) and reducing LDs …

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Novel Lipophagy Inducers as Potential Therapeutics for Lipid Metabolism Disorders

Rachel Njeim, Bassel Awada, Haley M. Donow, Haley Gye et autres

ABSTRACT Dysregulation of lipid homeostasis is associated with a wide range of pathologies encompassing neurological, metabolic, cardiovascular, oncological, and renal disorders. We previously showed that lipid droplet (LD) accumulation in podocytes contributes to the progression of diabetic kidney disease (DKD) and reducing …

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P-1346. Identification of aminoglycoside 6′-N-acetyltransferase type Ib small molecule inhibitors using mixture-based combinatorial libraries and structure-activity relationship studies

Jan Sklenicka, Tung Tran, Angel J. Magaña, María Soledad Ramirez et autres

Abstract Background The aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6’)-Ib] confers resistance to amikacin and other relevant aminoglycosides in Gram-negatives. To identify small molecule inhibitors of AAC(6’)-Ib that would overcome resistance, we utilized a strategy incorporating mixture-based combinatorial libraries, scaffold ranking, and positional scanning, …

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N-Branched Tricyclic Guanidines as Novel Melanocortin-3 Receptor Agonists and Melanocortin-4 Receptor Antagonists

Nicholas A. Weirath, Jonathan W. P. Zajac, Haley M. Donow, Travis LaVoi et autres

The melanocortin receptors are a class of centrally and peripherally expressed G protein-coupled receptors, of which the MC3R and MC4R subtypes are implicated in the regulation of appetite and energy homeostasis and can serve as potential therapeutic targets for disorders such as …

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A Therapeutic Lead Compound for Diabetic Kidney Disease with a Unique Lipophagy Activation Mechanism

Rachel Njeim, Haley Gye, Judith T. Molina David, Sandra Merscher et autres

Background: In 2021, 537 million people worldwide had diabetes, and this number is expected to increase to 783 million by 2045. Approximately 30% of individuals with diabetes develop Diabetic kidney disease (DKD), which ultimately leads to end stage renal failure. We previously …

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Structure–Activity Relationship of Pyrrolidine Pentamine Derivatives as Inhibitors of the Aminoglycoside 6′-N-Acetyltransferase Type Ib

Jan Sklenicka, Tung Tran, María Soledad Ramirez, Haley M. Donow et autres

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6′-N-acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome …

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Lab on a chip (LOC) platform for drug screening against the intracellular forms of Trypanosoma cruzi

María Fernanda Cadena, Gustavo Rosero-Yanez, Ramiro Isa-Jara, María Laura Belaunzarán et autres

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Structure-activity relationship of pyrrolidine pentamine derivatives as inhibitors of the aminoglycoside 6′- N -acetyltransferase type Ib

Jan Sklenicka, Tung Tran, María Soledad Ramirez, Haley M. Donow et autres

Abstract Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by aminoglycoside 6′- N -acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way …

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Discovery and Development of a Therapeutic Lead Compound for Diabetic Kidney Disease

Rachel Njeim, Haley M. Donow, Judith T. Molina David, Jeffrey D. Pressly et autres

Background: Diabetic kidney disease (DKD) is a leading cause of kidney failure worldwide. We previously demonstrated that the accumulation of lipid droplets (LDs) in podocytes leads to lipotoxicity and cell death in DKD. Drugs that lower circulating lipids do not halt DKD …

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Heterogeneous Nuclear Ribonucleoprotein C is an Indispensable Target in Acute Myeloid Leukemia

Vindhya Vijay, Amy Meacham, Lauren M. Katzell, Aaron Winer et autres

ABSTRACT Refractory disease is the greatest challenge in acute myeloid leukaemia (AML). Previously, we found vascular-associated AML cells as a source for refractory disease. In this study we use a bioassay of AML cells co-cultured on bone marrow-derived endothelial cells (BMECs) to …

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The Parallel Structure–Activity Relationship Screening of Three Compounds Identifies the Common Agonist Pharmacophore of Pyrrolidine Bis-Cyclic Guanidine Melanocortin-3 Receptor (MC3R) Small-Molecule Ligands

Mark D. Ericson, Katie T. Freeman, Travis LaVoi, Haley M. Donow et autres

The melanocortin receptors are involved in numerous physiological pathways, including appetite, skin and hair pigmentation, and steroidogenesis. In particular, the melanocortin-3 receptor (MC3R) is involved in fat storage, food intake, and energy homeostasis. Small-molecule ligands developed for the MC3R may serve as …

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