Lysophosphatidic acid (LPA) signaling has emerged as a central regulatory axis in both normal physiology and disease, orchestrating diverse cellular processes such as proliferation, survival, migratio Show more
Lysophosphatidic acid (LPA) signaling has emerged as a central regulatory axis in both normal physiology and disease, orchestrating diverse cellular processes such as proliferation, survival, migration, immune modulation, and tissue remodeling. Originally identified as a bioactive lipid that regulates smooth muscle contraction and vascular tone, LPA has since emerged as a pleiotropic signaling molecule implicated in multiple physiological systems and a wide spectrum of pathological states. These include cancer, neurodegenerative disorders, cardiovascular and metabolic syndromes, inflammatory conditions, and fibrotic diseases. Elevated LPA levels, overexpression of autotaxin (ATX), and aberrant activation of LPA receptors (LPARs) contribute to disease initiation and progression, positioning the LPA axis as both a diagnostic biomarker and a promising therapeutic target. This review describes the multimodal and multinodal organization of the LPA signaling network, detailing upstream biosynthesis, receptor diversity, and downstream effectors across diverse organ systems. Therapeutic strategies targeting ATX, LPARs, and intracellular mediators are critically assessed, along with a review of ongoing and emerging clinical trials. Furthermore, we introduce a context-aware AI-based neural network model to simulate LPA signaling dynamics, providing a framework for predictive modeling and personalized therapeutic interventions. By integrating mechanistic insights with adaptive computational frameworks, this review positions the LPA axis as a powerful and versatile target for systems biology-guided precision medicine strategies in both health and disease. Show less
Type 2 diabetes mellitus (T2DM) is a worldwide health problem that has raised major concerns to the public health community. This chronic condition typically results from the cell's inability to respo Show more
Type 2 diabetes mellitus (T2DM) is a worldwide health problem that has raised major concerns to the public health community. This chronic condition typically results from the cell's inability to respond to normal insulin levels. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the primary incretin hormones secreted from the intestinal tract. While clinical research has extensively explored the therapeutic potential of GLP-1R in addressing various T2DM-related abnormalities, the possibility of GIPR playing an important role in T2DM treatment is still under investigation. Evidence suggests that GIP is involved in the pathophysiology of T2DM. This chapter focuses on examining the role of GIP as a therapeutic molecule in combating T2DM, comparing the past, present, and future scenarios. Our goal is to delve into how GIP may impact pancreatic β-cell function, adipose tissue uptake, and lipid metabolism. Furthermore, we will elucidate the mechanistic functions of GIP and its receptors in relation to other clinical conditions like cardiovascular diseases, non-alcoholic fatty liver diseases, neurodegenerative diseases, and renal disorders. Additionally, this chapter will shed light on the latest advancements in pharmacological management for T2DM, highlighting potential structural modifications of GIP and the repurposing of drugs, while also addressing the challenges involved in bringing GIP-based treatments into clinical practice. Show less
Primary clear-cell adenocarcinoma of the urethra, a rare tumor that histomorphologically resembles clear-cell carcinoma of the female genital tract, occurs predominantly in women and is associated wit Show more
Primary clear-cell adenocarcinoma of the urethra, a rare tumor that histomorphologically resembles clear-cell carcinoma of the female genital tract, occurs predominantly in women and is associated with a relatively poor prognosis. The histogenesis of this rare urethral neoplasm has not been completely resolved, but it is thought to arise from either müllerian rests or metaplastic urothelium. Herein, we present comprehensive surgical pathological and cytopathological findings from a patient with primary urethral clear-cell adenocarcinoma and describe next-generation sequencing results for this patient's unique tumor-the first such reported characterization of molecular aberrations in urethral clear-cell adenocarcinoma at the transcriptomic and genomic levels. Transcriptome analysis revealed novel gene fusion candidates, including ANKRD28-FNDC3B. Whole-exome analysis demonstrated focal copy number loss at the SMAD4 and ARID2 loci and 38 somatic mutations, including a truncating mutation in ATM and a novel nonsynonymous mutation in ALK. Show less