It is well established that oxaliplatin, one of the three Pt(II) anticancer drugs approved worldwide, and phenanthriplatin, an important preclinical monofunctional Pt(II) anticancer drug, possess a di Show more
It is well established that oxaliplatin, one of the three Pt(II) anticancer drugs approved worldwide, and phenanthriplatin, an important preclinical monofunctional Pt(II) anticancer drug, possess a different mode of action from that of cisplatin and carboplatin, namely, the induction of nucleolar stress. The exact mechanisms that lead to Pt-induced nucleolar stress are, however, still poorly understood. As such, studies aimed at better understanding the biological targets of both oxaliplatin and phenanthriplatin are urgently needed to expand our understanding of Pt-induced nucleolar stress and guide the future design of Pt chemotherapeutics. One approach that has seen great success in the past is the use of Pt-click complexes to study the biological targets of Pt drugs. Herein, we report the synthesis and characterization of the first examples of click-capable phenanthriplatin complexes. Furthermore, through monitoring the relocalization of nucleolar proteins, RNA transcription levels, and DNA damage repair biomarker γH2AX, and by investigating their in vitro cytotoxicity, we show that these complexes successfully mimic the cellular responses observed for phenanthriplatin treatment in the same experiments. The click-capable phenanthriplatin derivatives described here expand the existing library of Pt-click complexes. Significantly they are suitable for studying nucleolar stress mechanisms and further elucidating the biological targets of Pt complexes. Show less
For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism t Show more
For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role. Show less
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence Show more
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence of many pathologies, particularly chronic non-communicable diseases such as obesity and diabetes. Here, we examine decades of research identifying the complex immunometabolic signaling networks and the cellular and molecular events that occur in the setting of altered nutrient and energy exposures and offer a historical perspective. Furthermore, we describe recent advances such as the discovery that a broad complement of immune cells play a role in immunometabolism and the emerging evidence that nutrients and metabolites modulate inflammatory pathways. Lastly, we discuss how this work may eventually lead to tangible therapeutic advancements to promote health. Show less