Biology subjects

Sano, Y.

Publications and source records attributed to Sano, Y..

6 recordsLinked to original sources

bioRxiv2026

Compact serum miRNA qPCR model for pancreatic cancer discrimination with independent and clinical validation

BackgroundFor pancreatic cancer, practical blood-based tests for early detection and postoperative surveillance remain elusive. We sought to develop a qPCR-measurable serum microRNA (miRNA) panel that robustly discriminates pancreatic cancer from non-cancer controls and other malignancies. MethodsWe profiled 255 serum miRNAs in batch 1 (n=72) and selected 27 candidates. Candidates were refined in batch 2 (n=552) and cross-batch evaluation was performed with batch 3 (n=391) to derive a miRNA model. Independent validation used batch 4 (n=616). Clinical relevance was assessed in an independent clinical cohort of resection patients with samples obtained preoperatively and at 1 and 12 months postoperatively. ResultsThe miRNA model trained on batches 2 and 3 achieved an area under the curve (AUC) of 0.91 and 0.83 for pancreatic cancer versus non-cancer controls and non-cancer plus other cancers, respectively, when independently validated in batch 4. Stage-wise AUCs in batch 4 were 0.91 (I), 0.94 (II), 0.86 (III) and 0.90 (IV). In the clinical batch, the score decreased postoperatively (preoperative vs month 1; p<0.01) and was higher in recurrence than non-recurrence (p<0.001). ConclusionsThe developed compact miRNA qPCR assay discriminated pancreatic cancer across independent assay batches and showed clinical relevance for postoperative surveillance. Clinical Trial RegistrationNot applicable.

cancer biology↗

bioRxiv2024

Wild gut microbiome suppresses the opportunistic pathogen Aeromonas in medaka under domesticated rearing conditions

BackgroundThe gut microbiome plays a crucial role in the metabolic health and pathogen resistance of various host animals. It is also well established that external environmental factors can influence the gut microbiome, leading to differences in its composition. However, the functional implications of these differences remain poorly understood. This study examined the gut microbiome of medaka (Oryzias latipes species complex) by comparing domesticated and wild populations, with the aim of gaining insights into the functional significance of their specific characteristics, particularly those of the wild-type microbiome. ResultsFor the comparative analysis of the gut microbiome, 48 domesticated and 122 wild medaka were collected from multiple laboratories, pet stores and streams across Japan. The results showed that wild medaka exhibited significantly higher gut microbiome diversity, with a broader range of bacterial members. In contrast, the gut microbiome of domesticated medaka harbored lower microbial diversity and was consistently dominated by Aeromonas, a typical opportunistic pathogen in fish. Additionally, 88.6% of Aeromonas isolates from domesticated medaka exhibited haemolytic activity. Moreover, a domesticated rearing experiment with wild populations showed no proliferation or dominance of Aeromonas in their gut, as observed in domesticated medaka. A further rearing experiment revealed that pre-exposing antibiotic-treated medaka to sediments from their natural habitats prevented Aeromonas colonisation, even when reared under domesticated conditions. ConclusionsThese findings suggest that the habitat-derived wild gut microbiome can inhibit Aeromonas proliferation in domesticated fish, highlighting its potential to mitigate opportunistic diseases in aquaculture.

microbiology↗

bioRxiv2021

IL-6 blockade suppresses the blood-brain barrier disorder, leading to prevention of onset of NMOSD

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy caused by antibodies against the aquaporin 4(AQP4) in end-feet of astrocytes. Breakdown of the blood-brain barrier (BBB) allowing ingress of AQP4 antibodies into the central nervous system (CNS) plays a key role in NMOSD. Although IL-6 blockade therapies such as satralizumab are effective in NMOSD, the therapeutic mechanism of IL-6 blockade, especially with respect to BBB disruption, are not fully understood because of the lack of the human models that are specialized to evaluate the BBB function. We constructed new in vitro human BBB models for evaluating continued barrier function, leukocyte transmigration and intracerebral transferability of IgGs utilizing the newly established triple co-culture system. In vitro and vivo experiments revealed that NMO-IgG increased intracerebral transferability of satralizumab, and that satralizumab suppressed the NMO-IgG-induced transmigration of T cells and barrier dysfunction. These results suggest that satralizumab, which can pass through the BBB in the presence of NMO-IgG, suppresses the barrier dysfunction and the disrupting controlled cellular infiltration at the BBB, leading to prevention of onset of NMOSD. One sentence summarySatralizumab and IL-6 blockade prevent lymphocyte migration and barrier dysfunction induced by NMO-IgG in EAE and novel triple co-culture BBB models.

immunology↗

bioRxiv2020

Suppression of amyloid-β secretion from neurons by cis-9, trans-11-octadecadienoic acid, an isomer of conjugated linoleic acid

Conjugated linoleic acid (CLA) comprises several geometric and positional isomers of the parental linoleic acid (LA). Two of the isomers, cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA) exert various biological activities. However, the effect of CLA on generation of neurotoxic amyloid-{beta} (A{beta}) protein remains unclear. We found that c9,t11CLA significantly suppressed generation of A{beta} in primary cultures of mouse neurons. CLA treatment did not affect the levels of {beta}-site APP-cleaving enzyme 1 (BACE1), a component of active {gamma}-secretase complex presenilin 1 amino-terminal fragment (PS1 NTF), or A{beta} protein precursor (APP) in cultured neurons. BACE1 activity in lysate of neurons treated with c9,t11 CLA, but not t10,c12 CLA, decreased slightly, although c9,t11 CLA did not directly affect the activity of recombinant BACE1. Interestingly, localization of BACE1 and APP in early endosomes increased in neurons treated with c9,t11 CLA; concomitantly, the localization of both proteins was reduced in late endosomes, where APP is predominantly cleaved by BACE1. c9,t11 CLA and t10,c12 CLA appeared to be incorporated into membrane phospholipids, as the level of CLA-containing lysophosphatidylcholine (CLA-LPC) increased dramatically in neurons incubated with CLA. Taken together, our findings indicate that accumulation of c9,t11 CLA-LPC, but not t10,c12 CLA-LPC, in neuronal membranes suppresses amyloidogenic cleavage of APP, thereby contributing to preservation of brain neurons by suppressing neurotoxic A{beta} production in aged subjects.

biochemistry↗

bioRxiv2020

Multi-organ signaling mobilizes tumor-associated erythroid cells expressing immune checkpoint molecules

Hematopoietic-derived cells are integral components of the tumor microenvironment and serve as critical mediators of tumor-host interactions. Cells derived from myeloid and lymphoid lineages perform well-established functions linked to cancer development, progression and response to therapy. It is unclear whether erythroid cells exert such host cell functions in cancer, but emerging evidence points to this possibility. Here we show that tumor-promoting environmental stress and tumor-induced physiological disruption trigger renal erythropoietin production and erythropoietin-dependent expansion of splenic erythroid cell populations in mice. These erythroid cells display molecular features indicative of an immature erythroid phenotype and express immune checkpoint molecules. Erythroid cells with similar properties are present in mouse and human tumor tissues. Antibody-mediated erythropoietin blockade or erythroid cell depletion reduces tumor growth. These findings reveal the potential of erythropoietin and erythroid cells as targets for cancer treatment.

cancer biology↗

bioRxiv2020

An in-vitro BBB-on-a-chip open model of human blood-brain barrier enabling advanced optical imaging

ABSTRACTWe describe here the design and implementation of an in-vitro BBB-on-a-chip open model system capable of reconstituting the microenvironment of the blood brain barrier. This system allows controlled unidirectional flow of nutrients and biologicals on the lumen of the artificial microvessel. This BBB-on-a-chip is suitable for high resolution electron microscopy and it is amenable for quantitative 3D live fluorescence imaging using spinning confocal disk or lattice light sheet microscopy (LLSM) to follow, for example the transcytosis across the BBB-like barrier of fluorescently-tagged biological, viruses or nanoparticles.Competing Interest StatementG.M. and B.O. are employees and shareholders of Biogen. T.K. is a visiting scientist at Biogen.View Full Text

bioengineering↗