The pathophysiology of hemorrhoids remains elusive; however, recent research has increasingly focused on the role of genetic and epigenetic mechanisms in this condition, offering prospects for targeted treatments. We conducted a review using PubMed, Embase, and Google Scholar, supplemented by citation searching, to summarize the current knowledge of the involvement of genetic and epigenetic mechanisms in hemorrhoids. Our review of 250 papers suggests that several genes, including FOXC2, NOX, NOS, and CALM3, may be responsible for the predisposing changes leading to the development of hemorrhoids. These genes have been associated with varicose veins, inflammation, and connective tissue alterations. Additionally, epigenetic mechanisms, particularly those mediated by miRNA, have been implicated in the clinical symptoms of hemorrhoids. While epigenetic regulation may influence inflammation, dilated vessels, and connective tissue degeneration, the exact mechanisms involved in these processes remain unclear. Furthermore, certain predisposing factors for hemorrhoids appear to involve both genetic and epigenetic mechanisms. This knowledge contributes to a better understanding of hemorrhoids and holds promise for developing novel therapeutic approaches.

The pathophysiology of hemorrhoids remains elusive; however, recent research has increasingly focused on the role of genetic and epigenetic mechanisms in this condition, offering prospects for targeted treatments. We conducted a review using PubMed, Embase, and Google Scholar, supplemented by citation searching, to summarize current knowledge of the involvement of genetic and epigenetic mechanisms in hemorrhoids. Our review of 250 papers suggests that several genes, including FOXC2, NOX, NOS, and CALM3, may be responsible for predisposing changes leading to the development of hemorrhoids. These genes have been associated with varicose veins, inflammation, and connective tissue alterations. Additionally, epigenetic mechanisms, particularly those mediated by miRNA, have been implicated in the clinical symptoms of hemorrhoids. While epigenetic regulation may influence inflammation, dilated vessels, and connective tissue degeneration, the exact mechanisms involved in these processes remain unclear. Furthermore, certain predisposing factors for hemorrhoids appear to involve both genetic and epigenetic mechanisms. This knowledge contributes to a better understanding of hemorrhoids and holds promise for developing novel therapeutic approaches.

Tympanosclerosis is a chronic middle ear disorder characterized by fibrosis, hyalinization, and calcification of the tympanic membrane and ossicles, which often results in conductive hearing loss. The objective of this systematic review was to synthesize current evidence on molecular pathways and genetic susceptibility factors contributing to the development of this condition. PubMed, Embase, Web of Science, and Google Scholar were searched up to December 2024. Eligible studies were original peer-reviewed articles in English investigating gene expression, genetic polymorphisms, or molecular signaling pathways in human or animal models. Risk of bias was assessed using standardized tools, and results were synthesized narratively due to heterogeneity. Twenty-five studies were included from 1815 screened records. Reported findings implicated inflammatory cytokines, such as TNF-α and IL-6, oxidative stress-related enzymes, including CAT, and iNOS, and bone remodeling pathways involving Wnt signaling, TGF-β1, and osteopontin. Polymorphisms in TLR4, NOS2 and NAT2 were associated with increased susceptibility or severity. Evidence remains limited but highlights potential biomarkers and therapeutic targets.