Farnesol prevents aging-related muscle weakness in mice through enhanced farnesylation of Parkin-interacting substrate.

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis. Reduced PGC-1α abundance is linked to skeletal muscle weakness in aging or pathological conditions, such as neurodegenerative diseases and diabetes; thus, elevating PGC-1α abundance might be a promising strategy to treat muscle aging. Here, we performed high-throughput screening and identified a natural compound, farnesol, as a potent inducer of PGC-1α.

Industrializing AI/ML during the end-to-end drug discovery process.

Drug discovery aims to select proper targets and drug candidates to address unmet clinical needs. The end-to-end drug discovery process includes all stages of drug discovery from target identification to drug candidate selection. Recently, several artificial intelligence and machine learning (AI/ML)-based drug discovery companies have attempted to build data-driven platforms spanning the end-to-end drug discovery process.

Diaminodiphenyl sulfone-induced parkin ameliorates age-dependent dopaminergic neuronal loss.

During normal aging, the number of dopaminergic (DA) neurons in the substantia nigra progressively diminishes, although massive DA neuronal loss is a hallmark sign of Parkinson's disease. Unfortunately, there is little known about the molecular events involved in age-related DA neuronal loss. In this study, we found that (1) the level of parkin was decreased in the cerebellum, brain stem, substantia nigra, and striatum of aged mice, (2) diaminodiphenyl sulfone (DDS) restored the level of parkin, (3) DDS prevented age-dependent DA neuronal loss, and (4) DDS protected SH-SY5Y cells from 1-methyl-4-phenylpyridinium and hydrogen peroxide.

Antibody-based molecular communication for targeted drug delivery systems.

Antibody-based drug delivery systems (ADDS) are established as the most promising therapeutic methods for the treatment of human cancers and other diseases. ADDS are composed of small molecules (antibodies) that selectively bind to receptors (antigens) expressed by the diseased cells. In this paper, the Molecular Communication (MC) paradigm, where the delivery of molecules is abstracted as the delivery of information, is extended to be applied to the design and engineering of ADDS.

A Molecular Communication System Model for Particulate Drug Delivery Systems.

The goal of a drug delivery system (DDS) is to convey a drug where the medication is needed, while, at the same time, preventing the drug from affecting other healthy parts of the body. Drugs composed of micro- or nano-sized particles (particulate DDS) that are able to cross barriers which prevent large particles from escaping the bloodstream are used in the most advanced solutions. Molecular communication (MC) is used as an abstraction of the propagation of drug particles in the body.

Correction: ensemble models of neutrophil trafficking in severe sepsis.

[This corrects the article on p. e1002422 in vol. 8.

Ensemble models of neutrophil trafficking in severe sepsis.

A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture)-induced sepsis in rats.

Modeling and analysis of retinoic acid induced differentiation of uncommitted precursor cells.

Manipulation of differentiation programs has therapeutic potential in a spectrum of human cancers and neurodegenerative disorders. In this study, we integrated computational and experimental methods to unravel the response of a lineage uncommitted precursor cell-line, HL-60, to Retinoic Acid (RA). HL-60 is a human myeloblastic leukemia cell-line used extensively to study human differentiation programs.

Ensembles of signal transduction models using Pareto Optimal Ensemble Techniques (POETs).

Mathematical modeling of complex gene expression programs is an emerging tool for understanding disease mechanisms. However, identification of large models sometimes requires training using qualitative, conflicting or even contradictory data sets. One strategy to address this challenge is to estimate experimentally constrained model ensembles using multiobjective optimization.

Modeling and analysis of the molecular basis of pain in sensory neurons.

Intracellular calcium dynamics are critical to cellular functions like pain transmission. Extracellular ATP plays an important role in modulating intracellular calcium levels by interacting with the P2 family of surface receptors. In this study, we developed a mechanistic mathematical model of ATP-induced P2 mediated calcium signaling in archetype sensory neurons.