bims-polyam 2025-01-05 papers

Issue of 2025–01–05
three papers selected by
Sebastian J. Hofer, University of Graz

BMC Oral Health. 2025 Jan 02. 25(1): 2

Salivary microbiota dysbiosis and elevated polyamine levels contribute to the severity of periodontal disease.

Md Haroon Rashid, Sandhya Pavan Kumar, Resma Rajan, Anitha Mamillapalli.

BACKGROUND: The oral cavity is a complex environment which harbours the second largest and most diverse microflora after the gastrointestinal tract. The bacteriome in the oral cavity plays a pivotal role in promoting the health and well-being of human beings. Gingivitis, an inflammation of the gingival tissue, arises due to plaque accumulation on the teeth, often leads to periodontitis. Progression of periodontitis resulting in clinical attachment loss, bone loss and eventually the tooth loss is poorly understood. The present study explores the transitions in microbioata, oxidative stress and polyamine levels during the disease evolution which can contribute to developing effective therapeutic approaches.
METHODS: Saliva samples were collected from seventy-two individuals after procuring informed consent who were either healthy, gingivitis or stage-specific periodontitis patients. Periodontitis stage was confirmed by clinical and radiographic analysis. Microbiota analysis was carried out by 16S rRNA sequencing on the Nanopore PromethIONsystem platform of Oxford Nanopore technologies. Polyamine levels were quantified with fluorescence spectrophotometer. Ornithine decarboxylase quantification was evaluated by ELISA method. Antioxidant levels of the salivary samples were measured by DPPH, SOD, and catalase assays. Autophagy was measured by acid phosphatase assay.
RESULT: The salivary microbiota exhibited significant changes in their abundance and diversity between healthy individuals and those with conditions such as gingivitis, and chronic periodontitis. A significant increase in polyamines and ornithine decarboxylase was found in gingivitis and various stages of periodontitis. Elevated oxidative stress observed in gingivitis and periodontitis could have resulted in cell death.
CONCLUSION: The current study shows the role of salivary microbiota and polyamines in gingivitis and different periodontitis stages. The progressive elevation of Streptococcus levels from gingivitis to periodontitis, coupled with polyamine concentrations, may serve as a promising identification marker for assessing the severity of periodontal disease. Insight into the oral bacterial flora and associated physiological changes provide a foundation for targeted therapeutic interventions in gingivitis and periodontitis diseases emphasising the importance of personalised oral health management strategies.

Keywords: Gingivitis; Oral microbiota; Oxidative stress; Periodontitis; Polyamines

DOI: https://doi.org/10.1186/s12903-024-05381-5

Alzheimers Dement. 2024 Dec;20 Suppl 1 e084861

Basic Science and Pathogenesis.

Wasana Pratchayasakul, Busarin Arunsak, Wichida Kaorop, Chayadom Maneechote, Suriphan Donchada, Aphisek Kongkaew, Titikorn Chunchai, Nipon Chattipakorn, Siriporn C Chattipakorn.

BACKGROUND: An increase in the development of learning deficit occurred during estrogen-deprived periods via the increment of systemic and brain oxidative stress, brain apoptosis, and synaptic dysplasticity. Although estrogen supplementation has been shown to improve the brain function in estrogen-deprived conditions, it can lead to several adverse effects. Therefore, the novel therapeutic approach with minimal side effects to protect brain function in estrogen-deprived conditions should be further investigated. Spermidine is a natural polyamine, which can be obtained orally from diet. In the brain, spermidine attenuated age-induced memory impairment and age-related locomotor activity loss via the modulation of autophagic process. However, the effects of spermidine on brain function in estrogen-deprived conditions have never been investigated.
METHOD: Eighteen female rats were assigned to sham-operated (Sham; n = 6), or estrogen-deprived group by ovariectomy (OVX; n = 12). Twelve weeks after surgery period, sham was received vehicle (normal saline; SV; n = 6) for additional 8 weeks. OVX groups were divided into two subgroups to receive either vehicle (normal saline; OV; n = 6) or spermidine (20 mg/kg/day; OS; n = 6) for an additional 8 weeks. At the end of the experimental period, all animals were taken to test the learning process with a novel objective location test. After that, blood and brain were collected to determine systemic and brain parameters.
RESULT: Ovariectomized rats showed the characteristic of estrogen deprivation, as indicated by decreased estradiol level when compared with those of sham rats (p<0.05, Figure 1). Spermidine did not increase the estradiol level of ovariectomized rats. Furthermore, systemic oxidative stress, hippocampal ROS production, hippocampal apoptosis, hippocampal autophagic imbalance, dendritic spine loss, synaptic dysplasticity, and learning deficit were observed in ovariectomized rats (p<0.05, Figure 1). Interestingly, spermidine attenuated these systemic and brain pathologies, which lead to improved learning process in ovariectomized rats (p<0.05, Figure 1).
CONCLUSION: These findings suggest that spermidine may be another therapeutic approach for improving systemic and brain functions in the case of estrogen deprivation.

DOI: https://doi.org/10.1002/alz.084861

Nature. 2025 Jan 01.

Aspartate signalling drives lung metastasis via alternative translation.

Lung metastases occur in up to 54% of patients with metastatic tumours1,2. Contributing factors to this high frequency include the physical properties of the pulmonary system and a less oxidative environment that may favour the survival of cancer cells3. Moreover, secreted factors from primary tumours alter immune cells and the extracellular matrix of the lung, creating a permissive pre-metastatic environment primed for the arriving cancer cells4,5. Nutrients are also primed during pre-metastatic niche formation6. Yet, whether and how nutrients available in organs in which tumours metastasize confer cancer cells with aggressive traits is mostly undefined. Here we found that pulmonary aspartate triggers a cellular signalling cascade in disseminated cancer cells, resulting in a translational programme that boosts aggressiveness of lung metastases. Specifically, we observe that patients and mice with breast cancer have high concentrations of aspartate in their lung interstitial fluid. This extracellular aspartate activates the ionotropic N-methyl-D-aspartate receptor in cancer cells, which promotes CREB-dependent expression of deoxyhypusine hydroxylase (DOHH). DOHH is essential for hypusination, a post-translational modification that is required for the activity of the non-classical translation initiation factor eIF5A. In turn, a translational programme with TGFβ signalling as a central hub promotes collagen synthesis in lung-disseminated breast cancer cells. We detected key proteins of this mechanism in lung metastases from patients with breast cancer. In summary, we found that aspartate, a classical biosynthesis metabolite, functions in the lung environment as an extracellular signalling molecule to promote aggressiveness of metastases.

DOI: https://doi.org/10.1038/s41586-024-08335-7