Propofol belongs to a class of molecules that are known to block learning and memory in mammals, including rodents and humans. Interestingly, learning and memory are not tied to the presence of a nervous system. There are several lines of evidence indicating that single-celled organisms also have the capacity for learning and memory which may be considered as basal intelligence. Here, we introduce a new experimental model for testing the learning ability of Physarum polycephalum, a model organism frequently used to study single-celled “intelligence”. In this study, the impact of propofol on Physarum’s “intelligence” was tested. The model consists of a labyrinth of subsequent bifurcations in which food (oat flakes soaked with coconut oil-derived medium chain triglycerides [MCT] and soybean oil-derived long chain triglycerides [LCT]) or propofol in MCT/LCT) is placed in one of each Y-branch. In this setting, it was tested whether Physarum memorized the rewarding branch. We saw that Physarum was a quick learner when capturing the first bifurcations of the maze; thereafter, the effect decreased, perhaps due to reaching a state of satiety. In contrast, when oat flakes were soaked with propofol, Physarum’s preference for oat flakes declined significantly. Several possible actions, including the blocking of gamma-aminobutyric acid (GABA) receptor signaling, are suggested to account for this behavior, many of which can be tested in our new model.

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect—the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris.

Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for novel, durable therapies. Similar to other non-Hodgkin lymphomas (NHLs), MF and SS have a greater incidence rate in males than females. The endocrine contribution to this sex difference is unknown. Although several studies could show a potential role of estrogen receptor β (ERβ) on NHL lymphomagenesis, its impact on CTCL development is unknown. In this study, we investigated LY500307, a selective ERβ agonist, as a potential treatment for CTCL. Our results show that LY500307 selectively reduced the viability of CTCL cells, sparing noncancerous skin cells. Liquid chromatography with tandem mass spectrometry analysis revealed that CTCL cells accumulated significantly higher concentrations of LY500307 than normal skin cells, likely contributing to its selective cytotoxicity. Mechanistically, LY500307 induced apoptosis, G2/M cell cycle arrest, and increased sensitivity to chemotherapeutic agents, particularly Monomethyl auristatin E. Furthermore, LY500307 treatment significantly reduced tumor growth in a CTCL xenograft mouse model without notable toxicity. These findings suggest LY500307 as a promising therapeutic agent for CTCL, warranting further clinical investigation, including the potential for topical applications.

The clinical application of immune checkpoint inhibitors represents a breakthrough progress in the treatment of metastasized melanoma and other tumor entities. In the present study, it was hypothesized that oligonucleotides (ODNs), known as modulators of the immune response, have an impact on the endogenous expression of checkpoint molecules, namely PD-L1 and PD-L2 (PD-L1/2). IFNγ-stimulated melanoma cells (A375, SK-Mel-28) were treated with different synthetically manufactured oligonucleotides which differed in sequence, length and backbone composition. It was found that a variety of different ODN sequences significantly suppressed PD-L1/2 expression. This effect was dependent on length and phosphorothioate (PTO) backbone. In particular, a sequence containing solely guanines (nCpG-6-PTO) was highly effective in downregulating PD-L1/2 at the protein, mRNA and promoter levels. Mechanistically, we gave evidence that ODNs with G-quartet-forming motifs suppress the interferon signaling axis (JAK/STAT/IRF1). Our findings identify a subset of ODNs as interesting pharmacological compounds that could expand the arsenal of targeted therapies to combat the immunological escape of tumor cells.

Chemotherapy poses both physical and psychological challenges for patients, prompting many to seek answers independently through online resources. This study investigates German Google search behavior regarding chemotherapy-related terms using Google AdWords data from September 2018 to September 2022 to gain insights into patient concerns and needs. A total of 1461 search terms associated with “chemotherapy” were identified, representing 1,749,312 to 28,958,400 search queries. These terms were categorized into four groups based on frequency and analyzed. Queries related to “adjuvant” and “neoadjuvant” chemotherapy, as well as “immunotherapy”, suggest potential confusion among patients. Breast cancer emerged as the most searched tumor type, with hair loss, its management, and dermatological issues being the most searched side effects. These findings underscore the role of search engines such as Google in facilitating access to healthcare information and provide valuable insights into patient thoughts and needs. Healthcare providers can leverage this information to deliver patient-centric care and optimize treatment outcomes.

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