Prostaglandins and thromboxane are lipid signaling molecules deriving from arachidonic acid by the action of the cyclooxygenase isoenzymes COX-1 and COX-2. The role of cyclooxygenases (particularly COX-2) and prostaglandins (particularly PGE₂) in cancer-related inflammation has been extensively investigated. In contrast, COX-1 has received less attention, although its expression increases in several human cancers and a pathogenetic role emerges from experimental models. COX-1 and COX-2 isoforms seem to operate in a coordinate manner in cancer pathophysiology, especially in the tumorigenesis process. However, in some cases, exemplified by the serous ovarian carcinoma, COX-1 plays a pivotal role, suggesting that other histopathological and molecular subtypes of cancer disease could share this feature. Importantly, the analysis of functional implications of COX-1-signaling, as well as of pharmacological action of COX-1-selective inhibitors, should not be restricted to the COX pathway and to the effects of prostaglandins already known for their ability of affecting the tumor phenotype. A knowledge-based choice of the most appropriate tumor cell models, and a major effort in investigating the COX-1 issue in the more general context of arachidonic acid metabolic network by using the systems biology approaches, should be strongly encouraged.

The effects of Ca²⁺-activated K⁺ (BK) channel modulation by Paxilline (PAX) (10⁻⁷–10⁻⁴ M), Iberiotoxin (IbTX) (0.1–1 × 10⁻⁶ M) and Resveratrol (RESV) (1–2 × 10⁻⁴ M) on cell cycle and proliferation, AKT1p^Ser473 phosphorylation, cell diameter, and BK currents were investigated in SH-SY5Y cells using Operetta-high-content-Imaging-System, ELISA-assay, impedentiometric counting method and patch-clamp technique, respectively. IbTX (4 × 10⁻⁷ M), PAX (5 × 10⁻⁵ M) and RESV (10⁻⁴ M) caused a maximal decrease of the outward K⁺ current at +30 mV (Vm) of −38.3 ± 10%, −31.9 ± 9% and −43 ± 8%, respectively, which was not reversible following washout and cell depolarization. After 6h of incubation, the drugs concentration dependently reduced proliferation. A maximal reduction of cell proliferation, respectively of −60 ± 8% for RESV (2 × 10⁻⁴ M) (IC50 = 1.50 × 10⁻⁴ M), −65 ± 6% for IbTX (10⁻⁶ M) (IC50 = 5 × 10⁻⁷ M), −97 ± 6% for PAX (1 × 10⁻⁴ M) (IC50 = 1.06 × 10⁻⁵ M) and AKT1p^ser473 dephosphorylation was observed. PAX induced a G1/G2 accumulation and contraction of the S-phase, reducing the nuclear area and cell diameter. IbTX induced G1 contraction and G2 accumulation reducing diameter. RESV induced G2 accumulation and S contraction reducing diameter. These drugs share common actions leading to a block of the surface membrane BK channels with cell depolarization and calcium influx, AKT1p^ser473 dephosphorylation by calcium-dependent phosphatase, accumulation in the G2 phase, and a reduction of diameter and proliferation. In addition, the PAX action against nuclear membrane BK channels potentiates its antiproliferative effects with early apoptosis.

Microarray data are a kind of numerical non-negative data used to collect gene expression profiles. Since the number of genes in DNA is huge, they are usually high dimensional, therefore they require dimensionality reduction and clustering techniques to extract useful information. In this paper we use NMF, non-negative matrix factorization, to analyze microarray data, and also develop “intelligent” results visualization with the aim to facilitate the analysis of the domain experts. For this purpose, a case study based on the analysis of the gene expression profiles (GEPs), representative of the human multiple myeloma diseases, was investigated in 40 human myeloma cell lines (HMCLs). The aim of the experiments was to study the genes involved in arachidonic acid metabolism in order to detect gene patterns that possibly could be connected to the different gene expression profiles of multiple myeloma. NMF results have been verified by western blotting analysis in six HMCLs of proteins expressed by some of the most abundantly expressed genes. The experiments showed the effectiveness of NMF in intelligently analyzing microarray data.

The microbiota–gut–brain axis (MGBA) is a complex signaling network linking the gut microbiota with central nervous system function. Growing evidence suggests that gut microbial dysbiosis contributes to neurodegenerative diseases (NDs) through mechanisms involving oxidative stress, neuroinflammation, disruption of the epithelial barrier, and altered microbial metabolite production. Unfortunately, the currently available therapies for NDs remain predominantly focused on symptomatic relief and do not modify the underlying disease progression. Natural bioactive compounds, particularly polyphenols, have emerged as promising multi-target modulators of the MGBA due to their pleiotropic effects across microbial, epithelial, immune, and neural compartments. This narrative review summarizes the available evidence on natural compounds and their microbial metabolites that target the MGBA, as evaluated in both in vitro and in vivo models. With a focus on Alzheimer disease, the molecular and cellular mechanisms underlying their effects across microbial, epithelial, immune, and neural compartments, as well as their potential therapeutic value through MGBA modulation, are discussed.