Tyroid hormones ,are key regulators of energy metabolism, involeved in a systemic conversion of T4 to T3. This reaction is catalyzed by selenoprotein iodothyronine deiodinase type 1 (DIO1). DIO1 protein is overexpressed in the liver and kidney tissue and it is regulated by nutritional factor, cytokines and oxidative stress. The present study aimed to explore, in an in vitro model of LPS-induced inflammation, the effects of a combination of selected nutrients—vitamin A, selenium, taurine, oleic acid, and resveratrol—on the expression and activity of DIO1 (Type 1 Iodothyronine Deiodinase) in Hepatoma cancer cells (HEPG2). The objective was to determine whether these bioactive compounds could mitigate inflammation-induced suppression of peripheral thyroid hormone activation, thereby supporting a more favorable redox and metabolic profile.To summarize, simoltaneous treatment with taurine, resveratrol, oleic acid and vitamin A not only prevents DIO-1 suppression, but also positively regulates its levels of expression offering a promising avenue for maintaining endocrine and metabolic health in frail, elderly, or oncologic patients and potentially across a broader spectrum of chronic inflammatory conditions.

Background/Objectives: Melanoma is the deadliest form of skin cancer. Resistance to alkylating agents such as Temozolomide (TMZ) and Dacarbazine (DTIC) limits their clinical benefit, as these drugs remain palliative options when immunotherapies and targeted treatments fail. CSA/ERCC8 is a key component of transcription-coupled nucleotide excision repair (TC-NER), a pathway responsible for removing UV-induced DNA lesions. In principle, loss of a DNA repair factor would be expected to increase carcinogenesis. However, although CSA loss-of-function causes Cockayne Syndrome (CS), affected patients do not exhibit increased skin cancer incidence, suggesting that CSA impairment promotes apoptosis rather than tumor development. This paradox raises the possibility that CSA inhibition may selectively target melanoma cell survival pathways. Methods: The expression of CSA/ERCC8 was analyzed by qRT-PCR and Western blot. ERCC8 was silenced using antisense oligonucleotides. Cell viability, apoptosis, cell cycle progression, drug sensitivity, and DNA damage were assessed by functional assays, including IC50 determination and Bliss analysis for drug interactions. Results: We identified CSA/ERCC8 as a driver of melanoma chemoresistance. CSA was markedly overexpressed in primary and metastatic melanoma cells. ERCC8 silencing reduced proliferation, induced apoptosis, and significantly enhanced sensitivity to low doses of TMZ and DTIC while sparing normal cells. Conclusions: CSA represents a promising therapeutic target to overcome chemoresistance in melanoma. Its inhibition enhances the efficacy and selectivity of alkylating agents, supporting its potential as a salvage strategy for refractory disease and warranting further preclinical and clinical investigation.