Thiol-Mediated Uptake of a Cysteine-Containing Nanobody for Anticancer Drug Delivery

The identification of tumor-specific biomarkers is one of the bottlenecks in the development of cancer therapies. Previous work revealed altered surface levels of reduced/oxidized cysteines in many cancers due to overexpression of redox-controlling proteins such as protein disulfide isomerases on the cell surface. Alterations in surface thiols can promote cell adhesion and metastasis, making thiols attractive targets for treatment. Few tools are available to study surface thiols on cancer cells and exploit them for theranostics. Here, we describe a nanobody (CB2) that specifically recognizes B cell lymphoma and breast cancer in a thiol-dependent manner. CB2 binding strictly requires the presence of a nonconserved cysteine in the antigen-binding region and correlates with elevated surface levels of free thiols on B cell lymphoma compared to healthy lymphocytes. Nanobody CB2 can induce complement-dependent cytotoxicity against lymphoma cells when functionalized with synthetic rhamnose trimers. Lymphoma cells internalize CB2 via thiol-mediated endocytosis which can be exploited to deliver cytotoxic agents. CB2 internalization combined with functionalization forms the basis for a wide range of diagnostic and therapeutic applications, rendering thiol-reactive nanobodies promising tools for targeting cancer

Mental health of UK hospitality Workers: Shame, self-criticism and self-reassurance

This study aimed to evaluate shame for mental health problems, and explore relationships between shame, self-criticism, self-reassurance, and mental health among UK hospitality workers, because this group of workers suffer from poor mental health yet report strong shame. An opportunity sample of 114 UK hospitality workers completed measures examining shame for mental health problems, self-criticism, self-reassurance, and mental health problems. A high proportion of workers scored over the midpoint in almost all the shame subscales. Shame, self-criticism, self-reassurance, and mental health were related to one another. External shame and self-criticism were positive predictors, and self-reassurance was a negative predictor for mental health problems. While self-criticism moderated the relationship between shame and mental health problems, self-reassurance did not. Online compassion training was recommended as it can reduce self-criticism and shame, can be undertaken without colleagues knowing and tailored to specific work patterns.N/