bims-polyam 2024-09-22 papers

Issue of 2024–09–22
three papers selected by
Sebastian J. Hofer, University of Graz

Proc Natl Acad Sci U S A. 2024 Sep 24. 121(39): e2404781121

The telencephalon is a neuronal substrate for systemic inflammatory responses in teleosts via polyamine metabolism.

Amir Mani, Farah Haddad, Daniel R Barreda, Irene Salinas.

Systemic inflammation elicits sickness behaviors and fever by engaging a complex neuronal circuitry that begins in the preoptic area of the hypothalamus. Ectotherms such as teleost fish display sickness behaviors in response to infection or inflammation, seeking warmer temperatures to enhance survival via behavioral fever responses. To date, the hypothalamus is the only brain region implicated in sickness behaviors and behavioral fever in teleosts. Yet, the complexity of neurobehavioral manifestations underlying sickness responses in teleosts suggests engagement of higher processing areas of the brain. Using in vivo models of systemic inflammation in rainbow trout, we find canonical pyrogenic cytokine responses in the hypothalamus whereas in the telencephalon and the optic tectum il-1b and tnfa expression is decoupled from il-6 expression. Polyamine metabolism changes, characterized by accumulation of putrescine and decreases in spermine and spermidine, are recorded in the telencephalon but not hypothalamus upon systemic injection of bacteria. While systemic inflammation causes canonical behavioral fever in trout, blockade of bacterial polyamine metabolism prior to injection abrogates behavioral fever, polyamine responses, and telencephalic but not hypothalamic cytokine responses. Combined, our work identifies the telencephalon as a neuronal substrate for brain responses to systemic inflammation in teleosts and uncovers the role of polyamines as critical chemical mediators in sickness behaviors.

Keywords: behavioral fever; polyamines; sickness behavior; telencephalon; teleosts

DOI: https://doi.org/10.1073/pnas.2404781121

Nutrients. 2024 Aug 29. pii: 2894. [Epub ahead of print]16(17):

Association of Polyamine Intake, Other Dietary Components, and Fecal Content of N-acetyl Putrescine and Cadaverine with Patients' Colorectal Lesions.

Eva Barreiro-Alonso, Paula Castro-Estrada, Manuel Sánchez, Pablo Peña-Iglesias, Lorena Suárez, Begoña Cantabrana.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection and the modification of risk factors, such as diet, can reduce its incidence. Among food components, polyamines are important for maintaining gastrointestinal health and are metabolites of gut microbiota. Their disruption is linked to CRC, making polyamines a potential marker of the disease. This study analyzed the relationship between dietary components, including polyamines, and the presence of polyamines in feces to determine whether their presence could contribute to predicting the occurrence of colorectal lesions in patients. In total, 59 participants of both sexes (aged 50 to 70 years) who had undergone colonoscopy screening for CRC (18 without and 41 with colorectal lesions) participated in the study. A nutritional survey and determination of fecal polyamine content were performed. Specific dietary components and putrescine levels were higher in patients with colorectal lesions. The diet ratio of putrescine-spermidine and the fecal content of N-acetyl putrescine and cadaverine were elevated in patients with precancerous lesions and adenocarcinomas, showing a potential predictive value for the presence of colorectal lesions. These findings suggest that N-acetyl putrescine and cadaverine could be complementary markers for the diagnosis of suspected colorectal lesions.

Keywords: colorectal cancer; feces N-acetyl putrescine; feces cadaverine; polyamine dietary intake

DOI: https://doi.org/10.3390/nu16172894

Adv Mater. 2024 Sep 17. e2409066

Multifunctional Copper-Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy.

Guoqing Zhu, Yulin Xie, Junrong Wang, Man Wang, Yanrong Qian, Qianqian Sun, Yunlu Dai, Chunxia Li.

The overexpression of polyamines in tumor cells contributes to the establishment of immunosuppressive microenvironment and facilitates tumor growth. Here, it have ingeniously designed multifunctional copper-piceatannol/HA nanopills (Cu-Pic/HA NPs) that effectively cause total intracellular polyamines depletion by inhibiting polyamines synthesis, depleting intracellular polyamines, and impairing polyamines uptake, resulting in enhanced pyroptosis and cuproptosis, thus activating a powerful immune response to achieve anti-tumor therapy. Mitochondrial dysfunction resulting from overall intracellular polyamines depletion not only leads to the surge of copper ions in mitochondria, thereby causing the aggregation of toxic proteins to induce cuproptosis, but also triggers the accumulation of reactive oxygen species (ROS) within mitochondria, which further upregulates the expression of zDHHC5 and zDHHC9 to promote the palmitoylation of gasdermin D (GSDMD) and GSDMD-N, ultimately inducing enhanced pyroptosis. Then the occurrence of enhanced pyroptosis and cuproptosis is conductive to remodel the immunosuppressive tumor microenvironment, thus activating anti-tumor immune responses and ultimately effectively inhibiting tumor growth and metastasis. This therapeutic strategy of enhanced pyroptosis and cuproptosis through comprehensive polyamines depletion provides a novel template for cancer immunotherapy.

Keywords: Cuproptosis; immunotherapy; metal‐phenolic; polyamines depletion; pyroptosis

DOI: https://doi.org/10.1002/adma.202409066