2,3,3,3-Tetrafluoro-2-(heptafluoropropoxy)-propanoate was designed to replace perfluorooctanoic acid (PFOA), which has been mostly phased out of U.S. production due to environmental persistence, detectable human, and wildlife serum concentrations, and reports of systemic toxicity. In rodent models, PFOA exposure suppresses T cell-dependent antibody responses (TDAR) and vaccine responses in exposed humans. To determine replacement compound effects on TDAR and related parameters, male and female C57BL/6 mice were gavaged with 0, 1, 10, or 100 mg/kg/day for 28 days. Mice immunized with antigen on day 24 were evaluated for TDAR and splenic lymphocyte subpopulations 5 days later. Serum and urine were collected for test compound concentrations and liver peroxisome proliferation was measured. Relative liver weight at 10 and 100 mg/kg and peroxisome proliferation at 100 mg/kg were increased in both sexes. TDAR was suppressed in females at 100 mg/kg. T lymphocyte numbers were increased in males at 100 mg/kg; B lymphocyte numbers were unchanged in both sexes. Females had less serum accumulation and higher clearance than males, and males had higher urine concentrations than females at all times and doses. While this PFOA-replacement compound appears less potent at suppressing TDAR relative to PFOA, it produces detectable changes in parameters affected by PFOA; further studies are necessary to determine its full immunomodulatory profile and potential synergism with other per- and polyfluoroalkyl substances of environmental concern.

Aflatoxin B₁ (AFB₁) is a class 1 carcinogen and a common food contaminant worldwide with widely uncontrolled human exposure. The ability of organic acids to transform AFB₁ into a known detoxified form, aflatoxin B_2a (AFB_2a), was investigated using high performance liquid chromatography-electrospray ionisation-time of flight mass spectrometry (HPLC/ESI/TOF/MS). The identity of the transformation product was confirmed by accurate mass measurement, chromatographic separation from other aflatoxins, H¹-nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy. Of the weak acids tested, citric acid was found to be the most effective for AFB_2a formation. At room temperature, 1 M citric acid was able to convert > 97% of AFB₁ to AFB_2a over 96 h of treatment. Up to 98% transformation was achieved by boiling AFB₁ in the presence of citric acid for 20 min. AFB₁ hydration after ingestion was explored by spiking AFB₁ into simulated gastric fluid containing citric acid. Under these conditions, > 71% of AFB₁ was hydrated to AFB_2a and did not show any reversion to the parent compound after being transferred to a neutral solution. These results provide a basis for a practical and effective method for detoxification of AFB₁ in contaminated foods.

Triple negative breast cancer (TNBC) is a subtype of breast cancer with typically poorer outcomes due to its aggressive clinical behavior and lack of targeted treatment options. Currently, treatment is limited to the administration of high-dose chemotherapeutics, which results in significant toxicities and drug resistance. As such, there is a need to de-escalate chemotherapeutic doses in TNBC while also retaining/improving treatment efficacy. Dietary polyphenols and omega-3 polyunsaturated fatty acids (PUFAs) have been demonstrated to have unique properties in experimental models of TNBC, improving the efficacy of doxorubicin and reversing multi-drug resistance. However, the pleiotropic nature of these compounds has caused their mechanisms to remain elusive, preventing the development of more potent mimetics to take advantage of their properties. Using untargeted metabolomics, we identify a diverse set of metabolites/metabolic pathways that are targeted by these compounds following treatment in MDA-MB-231 cells. Furthermore, we demonstrate that these chemosensitizers do not all target the same metabolic processes, but rather organize into distinct clusters based on similarities among metabolic targets. Common themes in metabolic targets included amino acid metabolism (particularly one-carbon and glutamine metabolism) and alterations in fatty acid oxidation. Moreover, doxorubicin treatment alone generally targeted different metabolites/pathways than chemosensitizers. This information provides novel insights into chemosensitization mechanisms in TNBC.