The mechanism of copper homeostasis and its role in disease

Copper(Cuprum)is an essential trace metal indispensable for the function of numerous enzymatic molecules implicated in cellular metabolism.Emerging evidence has demonstrated the role of copper in angiogenesis and cellular signaling.Moreover,raised copper levels have been detected in hepatocellular carcinoma and other cancers.An inherited or acquired copper imbalance,including inadequately low or excessively high copper levels,as well as inappropriate copper distribution in the body,is implicated in a number of diseases.In addition,a recent groundbreaking study identified a copperinduced type of programmed cell death named cuprotosis,the mechanism of which greatly deferred from that of other known cell death modes.The first part provides an overview of the regulation of copper homeostasis and discusses the underlying mechanisms of cuprotosis.In the second part,the authors focus on the functions of copper in liver diseases and other metabolic disorders,before discussing how this knowledge could contribute to the development of effective targets to treat such diseases.

Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Advances in Cuproptosis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) has already become a severe health risk and brings a lot of healthcare burden to the world. Apart from traditional HCC treatment strategies (surgery, liver transplantation, etc.), the emergence of immunotherapy targeting the immune microenvironment of HCC has brought new promise to patients with advanced HCC. However, adverse effects like drug resistance still exist. The liver is the main organ for storing copper ions, in copper overload can lead to liver function impairment and even the development of HCC. In recent years, a new mode of cell death has been identified, namely cuproptosis, a mode of programmed cell death that is dependent on copper ions and the tricarboxylic acid (TCA) cycle with mitochondria. Interestingly, a potential relationship between cuproptosis and the development of HCC has been found. Conclusively, this review provides an in-depth discussion of copper homeostasis in humans, the mechanism of cuproptosis, the potential impact of cuproptosis with HCC, and the therapeutic modalities of HCC that target cuproptosis, which provide new insights to promote the development of research targeting cuproptosis in HCC.

Review of copper and copper alloys as immune and antibacterial element

This review discussed the relationship among copper,human,and bacteria.Copper plays an important role in human immunity.Copper can boost human immune defense reactions at recommended intake level.The content mainly focused on copper antibacterial activity and copper antibacterial mechanisms.Conclusions stated that copper antibacterial activity is affected by copper homeostasis mechanisms in bacteria,adhesion,humidity,strain specificity,and manufacturing methods of antibacterial agents.For the preparation of particle antibacterial agents and surface antibacterial agents,this review discussed several manufacturing methods,such as sol−gel,cold spray,and biosynthesis belonging to chemical synthesis,physical synthesis,and biological synthesis,respectively.Sol−gel method contributes to the preparation of particle agents and surface agents.Cold spray technique is utilized in synthesis of surface copper agent.Biosynthesis is a novel technology which can be applied in nanoparticle agent preparation.

Copper Delivery by the Copper Chaperone for Chloroplast and Cytosolic Copper/Zinc- Superoxide Dismutases： Regulation and Unexpected Phenotypes in an Arabidopsis Mutant

Copper （Cu） is an important mineral nutrient found in chloroplasts as a cofactor associated with plastocyanin and Cu/Zn superoxide dismutase （Cu/ZnSOD）. Superoxide dismutases are metallo-enzymes found in most oxygenic organisms with proposed roles in reducing oxidative stress. Several recent studies in Arabidopsis have shown that microRNAs and a SQUAMOSA promoter binding protein-like7 （SPL7） transcription factor function to down-regulate the expression of many Cu-proteins, including Cu/ZnSOD in both plastids and the cytosol, during growth on low Cu. Plants contain the Cu Chaperone for SOD （CCS） that delivers Cu to Cu/ZnSODs, and, in Arabidopsis, both cytosolic and plastidic CCS versions are encoded by one gene. In this study, we demonstrate that Arabiclopsis CCS transcript levels are regulated by Cu, mediated by microRNA 398 that was not previously predicted to target CCS. The microRNA target site is conserved in CCS of Oryza sativa. The data suggest that Cu-regulated microRNAs may have more mRNA targets than was previously predicted. A CCS null mutant has no measurable SOD activity in the chloroplast and cytosol, indicating an absolute requirement for CCS. When the CCS null mutant was grown on high Cu media, it lacked both Fe superoxide dismutase （FeSOD） and Cu/ZnSOD activity. However, this did not lead to a visual phenotype and no photosynthetic deficiencies were detected, even after high light stress. These results indicate that Cu/ZnSOD is not a pivotal component of the photosynthetic anti-oxidant system during growth in laboratory conditions.