Essential Oil Constituents as Anti-Inflammatory and Neuroprotective Agents: An Insight through Microglia Modulation.

Microglia are key players in the brain's innate immune response, contributing to homeostatic and reparative functions but also to inflammatory and underlying mechanisms of neurodegeneration. Targeting microglia and modulating their function may have therapeutic potential for mitigating neuroinflammation and neurodegeneration. The anti-inflammatory properties of essential oils suggest that some of their components may be useful in regulating microglial function and microglial-associated neuroinflammation. This study, starting from the ethnopharmacological premises of the therapeutic benefits of aromatic plants, assessed the evidence for the essential oil modulation of microglia, investigating their potential pharmacological mechanisms. Current knowledge of the phytoconstituents, safety of essential oil components, and anti-inflammatory and potential neuroprotective effects were reviewed. This review encompasses essential oils of Thymus spp., Artemisia spp., Ziziphora clinopodioides, Valeriana jatamansi, Acorus spp., and others as well as some of their components including 1,8-cineole, ß-caryophyllene, ß-patchoulene, carvacrol, ß-ionone, eugenol, geraniol, menthol, linalool, thymol, α-asarone, and α-thujone. Essential oils that target PPAR/PI3K-Akt/MAPK signalling pathways could supplement other approaches to modulate microglial-associated inflammation to treat neurodegenerative diseases, particularly in cases where reactive microglia play a part in the pathophysiological mechanisms underlying neurodegeneration.

The Association of Death Receptors and TGF-ß1 Expression in Urothelial Bladder Cancer and Their Prognostic Significance.

Death receptor signalization that triggers the extrinsic apoptotic pathway and TGF-ß1 have important roles in urothelial carcinogenesis, with a complex interplay between them. The aim of this research was to assess the association of death receptors DR4, DR5, and FAS as well as TGF-ß1 immunohistochemical expression with the clinicopathological characteristics of urothelial bladder cancer (UBC) and to evaluate their prognostic significance. The decrease or loss of death receptors' expression was significantly associated with muscle-invasive tumors, while non-invasive UBC often retains the expression of death receptors, which are mutually strongly linked. High DR4 expression is a marker of low-grade tumors and UBC associated with exposition to known carcinogens. Conversely, TGF-ß1 was significantly associated with high tumor grade and advanced stage. High expression of DR4 and FAS indicates longer overall survival. High TGF-ß1 signifies an inferior outcome and is an independent predictor of adverse prognosis in UBC patients. This study reveals the expression profile of death receptors in UBC and their possible interconnection with TGF-ß1 and indicates independent prognostic significance of high FAS and TGF-ß1 expression in UBC, which may contribute to deciphering the enigma of UBC heterogeneity in light of the rapid development of novel and effective therapeutic approaches, including targeting of the TRAIL-induced apoptotic pathway.