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Renal and ovarian clear cell carcinoma (CCC) are both characterized by a clear cytoplasm and exhibit similar genomic alterations and clinical characteristics. We hypothesized that both CCCs may share clinical biomarker. Tissue factor pathway inhibitor 2 (TFPI2), a serine protease inhibitor, has emerged as a promising serum biomarker for ovarian CCC, and we evaluated the efficacy of TFPI2 as a biomarker for renal cell carcinoma (RCC). Serum samples were collected from patients with RCC and healthy volunteers, and TFPI2 levels were measured. Expression of TFPI2 in each cell type was evaluated using single-cell RNA sequencing. Survival analyses according to TFPI2 expression levels were performed based on publicly available databases. Serum TFPI2 was significantly elevated in patients with RCC compared to healthy volunteers, particularly those with clear cell histology. Metastatic RCC tumors exhibited higher TFPI2 than localized RCCs. Moreover, higher TFPI2 correlated with higher Fuhrman grades in clear cell RCC. Publicly available databases showed an association between TFPI2 expression and overall survival, particularly in clear cell RCC. Single-cell RNA sequencing confirmed TFPI2 expression in clear cell RCC and normal kidney tubular epithelial cells. TFPI2 has emerged as a potential serum biomarker for RCC, offering avenues for improved detection and prognostication., Competing Interests: Competing interests The authors declare no competing interests. Ethical approval This study was performed in accordance with the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects, after approval by the Institutional Ethics Committee of Yokohama City University (B181100031, B200800009, and B210300038). Informed consent Written informed consent was obtained from all patients for their data to be used for research purposes., (© 2024. The Author(s).)

Aging is closely associated with the increased morbidity and mortality of ischemic cardiovascular disease, at least partially through impaired angiogenic capacity. Endothelial cells (ECs) play a crucial role in angiogenesis, and their angiogenic capacity declines during aging. Spermidine is a naturally occurring polyamine, and its dietary supplementation has exhibited distinct anti-aging and healthy lifespan-extending effects in various species such as yeast, worms, flies, and mice. Here, we explore the effects of spermidine supplementation on the age-related decline in angiogenesis both in vitro and in vivo. Intracellular polyamine contents were reduced in replicative senescent ECs, which were subsequently recovered by spermidine supplementation. Our findings reveal that spermidine supplementation improved the declined angiogenic capacity of senescent ECs, including migration and tube-formation, without affecting the senescence phenotypes. Mechanistically, spermidine enhanced both autophagy and mitophagy, and improved mitochondrial quality in senescent ECs. Ischemia-induced neovascularization was assessed using the hind-limb ischemia model in mice. Limb blood flow recovery and neovascularization in the ischemic muscle were considerably impaired in aged mice compared to young ones. Of note, dietary spermidine significantly enhanced ischemia-induced angiogenesis, and improved the blood flow recovery in the ischemic limb, especially in aged mice. Our results reveal novel proangiogenic functions of spermidine, suggesting its therapeutic potential against ischemic disease., (© 2023. The Author(s).)

The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains to spread worldwide. COVID-19 is characterized by the striking high mortality in elderly; however, its mechanistic insights remain unclear. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Here, we experimentally investigated the SARS-CoV-2 infection in cultured human ECs, and performed a comparative analysis for post-infection molecular events using early passage and replicative senescent ECs. We found that; (1) SARS-CoV-2 infects ECs but does not replicate and disappears in 72 hours without causing severe cell damage, (2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, (3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, (4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in early passage ECs, which might causes further exacerbated dysfunction in senescent ECs. These data suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients., (© 2022. The Author(s).)

Threespine sticklebacks of the genus Gasterosteus, are small teleost fish that are widely distributed across the northern hemisphere. The fish is believed to have two major types of life history, freshwater resident and anadromous; however little is known about their migration ecology. Comprehensive research on the migratory history, habitat use and relative composition of migratory types was conducted by analysing the otolith strontium and calcium concentrations collected in various environments of northern Japan. The present study first demonstrated that approximately 90% of morphologically anadromous sticklebacks had estuarine resident migration pattern, consistently living in brackish water and/or marine environments through their life cycle without any time spent in freshwater. The dominant occurrence of the estuarine resident was temporally and spatially consistent with their general migration ecology. The estuarine resident is thought to be the ancestral migrations of G. aculeatus and G. nipponicus, which thereafter gradually immigrated into freshwater habitats and settled in the anadromous form in both species and finally became the freshwater resident G. aculeatus. Thus, this study provides novel insights into the evolutionary migration of these fish, as well as a new discovery regarding the dominant migratory history and habitat use in threespine sticklebacks.