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1. Logic-based modeling of inflammatory macrophage cross talk with glomerular endothelial cells in diabetic kidney disease

   https://doi.org/10.1152/ajprenal.00362.2024  

   Patidar, Krutika; Ford_Versypt, Ashlee N (July 2025, American Journal of Physiology-Renal Physiology)

   This work provides a novel analysis of signaling cross talk between macrophages and glomerular endothelial cells in the early stage of diabetic kidney disease. A logic-based mathematical modeling approach identified vital signaling molecules and interactions that regulate glucose-mediated inflammation in glomerular endothelial cells and cause endothelial dysfunction in the diabetic kidney. Simulated interactions among vascular endothelial growth factor receptor 1, nitric oxide, and calcium significantly affected the intercellular junction proteins between glomerular endothelial cells. 

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2. Mechanosensation to inflammation: Roles for YAP/TAZ in innate immune cells

   https://doi.org/10.1126/scisignal.adc9656  

   Meli, Vijaykumar S.; Veerasubramanian, Praveen Krishna; Downing, Timothy L.; Wang, Wenqi; Liu, Wendy F. (May 2023, Science Signaling)

   Innate immune cells are responsible for eliminating foreign infectious agents and cellular debris, and their ability to perceive, respond to, and integrate biochemical and mechanical cues from their microenvironment eventually determines their behavior. In response to tissue injury, pathogen invasion, or a biomaterial implant, immune cells activate many pathways to initiate inflammation in the tissue. In addition to common inflammatory pathways, studies have demonstrated the role of the mechanosensitive proteins and transcriptional coactivators YAP and TAZ (YAP/TAZ) in inflammation and immunity. We review our knowledge of YAP/TAZ in controlling inflammation and immunity in innate immune cells. Furthermore, we discuss the roles of YAP/TAZ in inflammatory diseases, wound healing, and tissue regeneration and how they integrate mechanical cues with biochemical signaling during disease progression. Last, we comment on possible approaches that can be exploited to harness the therapeutic potential of YAP/TAZ in inflammatory diseases. 

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3. Plasma Protein Risk Scores for Mild Cognitive Impairment and Alzheimer Disease in the Framingham Heart Study

   Rehman, H; Ang, TFA; Tao, Q; Au, R; Farrer, LA; Qiu, W; Zhang, X (April 2025, Alzheimers dementia)

   INTRODUCTION: It is unclear whether aggregated plasma protein risk scores (PPRS) could be useful to predict the risks of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). METHODS: The Cox proportional hazard model with the LASSO penalty was used to build the PPRS for MCI and AD in 1,515 Framingham Heart Study Generation2 with 1,128 proteins measured in plasma at exam 5 [cognitive normal (CN)=1,258, MCI=129, AD=128]. RESULTS: MCI PPRS had a hazard ratio (HR) of 6.97[5.34,9.12], with a discriminating power (C-index=82.52%). AD PPRS had an HR of 5.74[4.67,7.05] (C-index=88.15%). Both PPRSs were also significantly associated with cognitive changes, brain-atrophy, and plasma AD biomarkers. Proteins in the MCI and AD PPRSs were enriched in several pathways related to leukocyte, chemotaxis, immunity, inflammation, and cellular migration. DISCUSSION: This study suggests that PPRS serve well to predict the risk of developing MCI and AD as well as cognitive changes and AD related pathogenesis in the brain. 

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4. Gut Microbiome: Profound Implications for Diet and Disease

   https://doi.org/10.3390/nu11071613  

   Hills, Ronald D.; Pontefract, Benjamin A.; Mishcon, Hillary R.; Black, Cody A.; Sutton, Steven C.; Theberge, Cory R. (July 2019, Nutrients)

   The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease. 

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5. Probing the Interactions of LRP1 Ectodomain-Derived Peptides with Fibrillar Tau Protein and Its Impact on Cellular Internalization

   https://doi.org/10.3390/app13020853  

   Boder, E. Josephine; Goncalves, Beatriz G.; Lebedenko, Charlotta G.; Banerjee, Ipsita A. (January 2023, Applied Sciences)

   Cellular internalization and the spreading of misfolded tau have become increasingly important for elucidating the mechanism of Tau pathology involved in Alzheimer’s disease (AD). The low-density lipoprotein-related receptor 1 (LRP1) has been implicated in the internalization of fibrillar tau. In this work, we utilized homology modeling to model the Cluster 2 domain of LRP1 and determined that a 23-amino-acid sequence is involved in binding to paired helical filaments (PHF) of Tau. Fourteen short peptide segments derived from this ectodomain region were then designed and docked with PHF Tau. Molecular dynamics studies of the optimal peptides bound to PHF Tau demonstrated that the peptides formed critical contacts through Lys and Gln residues with Tau. Based on the computational results, flow cytometry, AFM, SPR analysis and CD studies were conducted to examine binding and cellular internalization. The results showed that the peptide sequence TauRP (1–14) (DNSDEENCES) was not only associated with fibrillar Tau but was also able to mitigate its cellular internalization in LRP1-expressed HEK-293 cells. Preliminary docking studies with Aβ (1–42) revealed that the peptides also bound to Aβ (1–42). While this study focused on the CCR2 domain of LRP1 to design peptide sequences to mitigate Tau internalization, the work can be extended to other domains of the LRP1 receptor or other receptors to examine if the cellular internalization of fibrillar Tau can be deterred. These findings show that short peptides derived from the LRP1 receptor can alter the internalization of its ligands. 

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