Homogentisic acid metabolism inhibits papillary thyroid carcinoma proliferation through ROS and p21-induced cell cycle arrest.

Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues. We evaluated the potential of HGA as a novel molecular marker in the diagnosis of PTC tumors, as well as its ability to indicate the degree of malignancy. Studies have further shown that HGA contributes to reactive oxygen species (ROS) associated oxidative stress, leading to toxicity and inhibition of proliferation. In addition, HGA caused an increase in p21 expression levels in PTC cells and induced G1 arrest. Moreover, we found that the low HGA content in PTC tumors was due to the low expression levels of tyrosine aminotransferase (TAT) and p-hydroxyphenylpyruvate hydroxylase (HPD), which catalyze the conversion of tyrosine to HGA. The low expression levels of TAT and HPD are strongly associated with a higher probability of PTC tumor invasion and metastasis. Our study demonstrates that HGA could be used to diagnose PTC and provides mechanisms linking altered HGA levels to the biological behavior of PTC tumors.

Codelivery of triptolide and IFN-γ to boost antitumor immunity for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a specific type of breast cancer that exhibits poor prognosis and complex tumor heterogeneity. The unique immune tumor microenvironment reveals great potential of immunotherapy in TNBC. Triptolide, a potential regulator of immune-related signaling, has shown potent antitumor activity in TNBC. However, the molecular mechanism of triptolide in TNBC is still controversial. This study identified interferon-γ (IFN-γ) as a therapeutical target of triptolide based on the analysis of prognostic biomarkers in TNBC. IFN-γ is an important component of immunotherapy and contributes to antitumor immune activation. Triptolide was found to significantly reverse the IFN-γ-inducible programmed death-ligand 1 (PD-L1) in TNBC. The combined treatment of triptolide and IFN-γ in a hydrogel delivery system remarkably induced the cytotoxic CD8 + T lymphocytes activation, showing a synergistic effect on the potent tumor inhibition.

Exploration of the effect of simultaneous removal of EDCs in the treatment process of different types of wastewater.

The SPE-HPLC-MS/MS method was used to investigate the concentration distribution of nine types of estrogens in 18 locations of pollution source along the Jiuzhou River belonging to river systems in Guangdong province and Guangxi Zhuang autonomous region in China, and the estrogenic activity and potential ecological risks were evaluated by calculating the estradiol equivalency (EEQ). The results showed that the calculated estradiol equivalents (cEEQs) of wastewater treatment plants from 17 locations were all higher than 1 ng/L. To further study the removal effect of the treatment process on the estrogens, the pig breeding wastewater from P4 and the municipal wastewater from P13, as well as the black-odorous water, were sampled and surveyed during the entire process. It turned out that estrogens were effectively removed after nitrification activated sludge treatment. Meanwhile, there was a positive correlation between the removal of NH3-N, total nitrogen (TN) and total phosphorus (TP) and the removal of endocrine disrupting chemicals (EDCs). It is shown in the study the secondary treatment process has achieved a significant effect on the removal of estrogen in both the wet and dry periods and that there has been a positive correlation between the activities of total phosphorus compounds, nitrogen-based compounds and the removal of EDCs.