Publications by authors named "Yukihiko Sugimoto"

Article Synopsis
  • Embryo implantation is essential for a healthy pregnancy and is influenced by changes in gene expression and metabolism in the uterus, which respond to hormones and embryo signals.
  • Researchers used spatial transcriptomic analysis to identify that lipid metabolism, particularly pathways related to arachidonic acid, is important in the uterus during implantation.
  • The study found that the COX2 enzyme plays a crucial role in successful implantation, while the absence of COX1 or COX2 leads to impaired pregnancy or infertility, highlighting the distinct functions of each enzyme in this process.*
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Key Points: Omega-3 polyunsaturated fatty acids prevent AKI to CKD transition and renal fibrosis. Eicosapentaenoic acid metabolites 18-hydroxyeicosapentaenoic acid, 17,18-epoxyeicosatetraenoic acid, and 17,18-dihydroxyeicosatetraenoic acid have antifibrotic effects.

Background: AKI is an established risk factor for developing CKD.

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  • Researchers examined the roles of prostaglandins (PGs) in the uterus by studying various PG receptor expressions during pregnancy, finding key receptors in luminal and stromal cells.
  • The expression of the DP receptor was notably induced in stromal cells after embryo attachment, aligning with COX-2 expression, while both PGD and PGE were synthesized in significant amounts during implantation.
  • The study revealed that the DP and EP4 receptors play crucial roles in the process of decidualization, with pharmacological interventions suggesting their coordinated functions despite the lack of impact from DP/EP2 double deficiency.
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  • Prostaglandins are compounds that affect biological rhythms by activating specific receptors, but the relationship between the prostaglandin F receptor and these rhythms is not well understood.
  • Research on mutant mice showed that their locomotor period lengths were longer in constant dark conditions compared to normal mice, along with altered expression of clock genes in the suprachiasmatic nucleus and liver.
  • The study suggests that plasma levels of prostaglandin F exhibit a circadian rhythm, which may influence the expression of clock genes, indicating that drugs targeting this pathway could impact biological clock cycles.
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  • The Concise Guide to PHARMACOLOGY 2023/24 offers a summarized overview of approximately 1800 drug targets and around 6000 interactions with 3900 ligands, mostly in a tabular format.
  • It focuses on selective pharmacology and includes links to an open access knowledgebase for more detailed drug information.
  • The guide divides drug targets into six major categories, providing essential summaries and guidance based on the latest pharmacological data available as of mid-2023, while serving as an official resource by the International Union of Basic and Clinical Pharmacology.
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In vertebrates, female receptivity to male courtship is highly dependent on ovarian secretion of estrogens and prostaglandins. We recently identified female-specific neurons in the medaka (Oryzias latipes) preoptic area that express Npba, a neuropeptide mediating female sexual receptivity, in response to ovarian estrogens. Here we show by transcriptomic analysis that these neurons express a multitude of neuropeptides, in addition to Npba, in an ovarian-dependent manner, and we thus termed them female-specific, sex steroid-responsive peptidergic (FeSP) neurons.

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  • Prostanoids are lipid mediators derived from arachidonic acid through cyclooxygenase activity, influencing various biological functions by interacting with specific cell receptors.
  • They are known for roles in fever, pain, and inflammation, but also significantly contribute to processes like female reproduction and maintaining vascular and gut health.
  • Recent studies using mice without prostanoid receptors have revealed new functions of these mediators, highlighting their potential as targets for treating metabolic disorders through mechanisms related to fat cell regulation.
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  • The study investigates the impact of ω3 polyunsaturated fatty acids (PUFAs) on female reproduction by comparing mice fed with linseed oil (ω3-rich) and soybean oil (ω6-rich).
  • Results show that while the levels of certain fatty acids and prostaglandins vary between the two diets, no significant differences in fertility indicators like luteolysis and parturition were observed in the ω3 diet group.
  • The findings imply there is a mechanism in linseed oil-fed mice that maintains sufficient levels of 'luteolytic' prostaglandin (PGF) for reproductive processes, even with lower ω6 PUFA availability.
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A simple methylenedioxy dibromoindole alkaloid, amakusamine (), was isolated from a marine sponge of the genus , and its structure was determined from spectroscopic data, time-dependent density-functional theory calculations, and synthesis. Compound inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinuclear osteoclasts with an IC value of 10.5 μM in RAW264 cells.

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  • The Concise Guide to Pharmacology 2021/22 offers a streamlined overview of nearly 1900 human drug targets, focusing on selective pharmacology and organized mainly in tables for quick reference.
  • The guide serves as a reliable, citable resource that distills extensive online content while ensuring it reflects the status as of mid-2021, distinct from ongoing database updates.
  • Key pharmacological targets include G protein-coupled receptors, ion channels, and enzymes, with official nomenclature and references provided to assist further research and understanding.
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  • - Fifteen new isopimarane-type diterpenes (taichunins E-S) and one new 20-isopimarane (taichunin T) were isolated from a specific strain (IBT 19404), alongside four known compounds.
  • - The structures of these new compounds were identified using NMR and mass spectroscopy, with their configurations analyzed through NOESY and TDDFT calculations of ECD spectra.
  • - Taichunins G, K, and N showed complete inhibition of RANKL-induced osteoclast formation in RAW264 cells at 5 μM, and one compound exhibited 92% inhibition at just 0.2 μM.
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  • Epicutaneous (e.c.) allergen exposure plays a crucial role in developing allergic diseases, and proteases in allergens, like those from house dust mites, contribute to this process while being regulated by prostanoids from cyclooxygenase (COX) pathways.
  • In an experiment with mice, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) during e.c. sensitization to a protease allergen, papain, showed increased immune responses, including higher IgE levels and cytokine production linked to allergic reactions.
  • The study concludes that COX-derived prostanoids have a suppressive effect on the immune response, particularly on Th2 and Th17 cells, suggesting that inhibiting COX pathways
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  • * The study identifies the role of the adipocyte prostaglandin E-EP4 receptor signaling in regulating basal lipolysis and fat distribution, especially during periods of feeding and fasting.
  • * The PGE-EP4 pathway interacts with insulin to maintain balanced lipolysis, and disturbances in this signaling may contribute to a condition known as "metabolically healthy obesity."
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  • BLT1 is a chemotactic receptor found in certain immune cells, including granulocytes and macrophages, but its function in dendritic cells (DCs) is not well understood.
  • Researchers identified two distinct subsets of DCs defined by BLT1 expression and observed that these subsets migrate differently in response to specific chemical signals (LTB and CCL21).
  • Their studies suggest that BLT1 DCs play a significant role in aggravating allergic responses and influence T cell activity by producing specific cytokines, revealing important insights into the regulatory functions of these immune cells.
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  • Mice lacking the protein PACAP have reduced ability to adjust their internal clocks in response to light.* -
  • Gene analysis of specific brain regions revealed that a protein called L-PGDS plays a role in their impaired response to light during late night.* -
  • Mice without the DP2/CRTH2 receptor also show difficulties in advancing their internal clocks with light, suggesting that L-PGDS signals through this receptor for light-induced phase adjustment.*
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  • * PGI and PGE interact with specific receptors (IP and EP1-4), which are prevalent throughout the body and impact various physiological and pathological processes.
  • * Recent research highlights differences between humans and rodents regarding the functions of these receptors, suggesting their potential as therapeutic targets in various diseases based on recent scientific findings.
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  • The study explores the relationship between changes in fatty acid (FA) composition and renal proximal tubulopathy, which is significant in kidney disease.
  • Researchers used mouse models of acute kidney injury (AKI) and chronic kidney disease (CKD) to conduct their analysis and measured renal FA composition using GC-MS.
  • Results indicated that increased levels of stearic acid (C18:0) contribute to tubular toxicity and renal stress, with potential therapeutic implications involving targeting the AOPPs-Elovl6 system to treat tubulopathy.*
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  • Thymic involution, characterized by a decrease in thymus size and function, can lead to immunodeficiency disorders, prompting research into its underlying molecular mechanisms.
  • A study using a murine model of acute diet restriction showed that this dietary change alters cytokine expression, promoting a shift from T helper 1 (Th1) to T helper 2 (Th2) cell phenotypes.
  • The increased production of prostanoids during thymic involution was linked to these changes in T cell polarization, and inhibiting prostanoid synthesis with non-steroidal anti-inflammatory drugs modified cytokine expression in the thymus without stopping its size reduction.
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Cell competition is a biological process by which unfit cells are eliminated from "cell society." We previously showed that cultured mammalian epithelial Madin-Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by "normal" MDCK cells. However, the molecular mechanism underlying the elimination of active YAP-expressing cells was unknown.

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  • The study compared the effects of omidenepag (OMD) and prostaglandin F receptor agonists (FP agonists) on fat cell formation (adipogenesis) in mouse cells (3T3-L1).
  • It was found that while FP agonists like latanoprost free acid (LAT-A) and prostaglandin F (PGF) significantly reduced fat droplet accumulation and gene expression during fat cell differentiation, OMD did not show any noticeable effect even at higher concentrations.
  • The research concluded that OMD, acting as a selective EP2 receptor agonist, does not influence adipocyte differentiation, contrasting with the significant inhibitory effects of FP agonists.
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  • Parturition, the process of giving birth in placental mammals, involves complex molecular mechanisms that are not yet fully understood, particularly regarding the role of oxytocin and the PGF2α receptor.
  • In experiments with mice lacking oxytocin receptors, researchers found that certain genes crucial for uterine contractions were not properly induced, but the PGF2α receptor expression remained unaffected.
  • Further testing with double knockout mice revealed that while pregnancy rates were normal, these mice could not undergo successful parturition due to high progesterone levels; however, the administration of a progesterone antagonist allowed some to deliver, highlighting the critical roles of both oxytocin/oxytocin receptor and PGF2α receptor in the bir
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Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear.

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  • - The study explores the role of p38 mitogen-activated protein kinase in psoriasis, showing that its activation can lead to psoriatic inflammation in mouse models.
  • - Daily application of the p38 activator anisomycin on mouse skin resulted in psoriatic traits, such as skin thickening and increased inflammatory markers, but these effects were reduced after using a p38 inhibitor, BIRB796.
  • - The findings suggest that targeting p38 could be a promising therapeutic approach for treating psoriasis, as the skin responses were similar to those observed in human psoriasis cases.
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  • Lymphatic endothelial cells originate from venous endothelial cells during embryonic development, but the exact molecular processes are not fully understood.
  • This study reveals that prostaglandin E (PGE) plays a crucial role in lymphatic development via the EP3 receptor; interfering with this pathway disrupts lymphatic specification in zebrafish.
  • The research also indicates that the EP3 receptor is necessary for the expression of key factors like sox18 and nr2f2, which are vital for lymphatic development, highlighting the importance of the COX1-derived PGE-EP3 signaling pathway.
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  • - Prostaglandins (PGs), primarily derived from arachidonic acid via COX enzymes, play a key role in various physiological and pathological processes, with Prostaglandin E2 (PGE2) being the most prevalent type across tissues.
  • - PGE2 influences inflammation and immune responses through its interaction with four receptor subtypes (EP1-4), where it exacerbates conditions by activating mast cells and promoting specific T cell responses.
  • - Recent studies in mice lacking specific PG receptors have enhanced our understanding of how PGE2 contributes to inflammation and autoimmune diseases, leading to discussions on potential drug development targeting these receptors for treatment.
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