The Cd/Zn Axis: Emerging Concepts in Cellular Fate and Cytotoxicity.

Cadmium (Cd) is a toxic and carcinogenic substance that is present in the natural environment. The underlying biomolecular mechanisms of Cd toxicity are not completely understood, and it continues to be a significant research target due to its impact on public health. The primary routes of exposure are through ingestion of contaminated food and water and inhalation. Cd's long biological half-life of 10-30 years allows it to accumulate in the body, leading to organ dysfunction notably in the kidney, liver, bone, and lungs. Cd has similar biochemical characteristics to Zinc (Zn). It shares the import transporters, ZIP8 and ZIP14, to enter the cells. This competitive behavior can be observed in multiple instances throughout the progression of Cd toxicity. Future studies on the biochemical interactions of Cd and Zn will elucidate the potential protective effects of Zn supplementation in reducing the effects of Cd toxicity. In addition, research can be focused on discovering key proteins and effective pathways for Cd elimination that confer fewer adverse effects than current antioxidant therapies.

Guanylate Binding Protein 1 (GBP1): A Key Protein in Inflammatory Pyroptosis.

Scientists recently made a significant breakthrough in the recognition of pathogens via guanylate binding protein 1 (GBP1). Wandel et al. [1] in Nature Immunology described their findings where GBP1 acts as a pattern recognition receptor that directly connects to lipopolysaccharide (LPS). GBP1 identifies gram-negative bacteria such as the enteric pathogen, Salmonella enterica serovar Typhimurium, that enter the cytoplasm of the host cell. GBP1 then quickly connects to LPS and stimulates the assembly of more GBPs in the order of GBP2, GBP3, and GBP4. Subsequently, inflammatory caspase-4 arrives at the GBP1-4 activation platform. Next, the activated caspase-4 drives the cleavage of Gasdermin D, triggering the release of the pro-inflammatory cytokine, interleukin-18 (IL-18) leading to inflammatory pyroptosis and cell death. Not only do these remarkable results expand our current understanding of GBP1, but they also carry the potential to develop therapeutic targets for inflammasome-mediated human disorders.