Journal of Physiological Sciences最新文献

{"title":"Orai1- and STIM1-mediated calcium signaling controls PD-L1 expression and modulates antitumor immunity in oral cancer.","authors":"Eriko Yamashita, Soichiro Ishikawa, Yuto Mizuno, Yu Iida, Mio Mochizuki, Akane Nagasako, Michiko Endo, Kohei Osawa, Yayoi Kimura, Takayuki Fujita, Utako Yokoyama, Kenji Mitsudo, Yoshihiro Ishikawa, Masanari Umemura","doi":"10.1016/j.jphyss.2026.100063","DOIUrl":"10.1016/j.jphyss.2026.100063","url":null,"abstract":"<p><p>This study investigated the regulation of PD-L1 expression by calcium signaling in oral squamous cell carcinoma (OSCC). We found that IFN-γ stimulation markedly altered the intracellular proteome and activated calcium-associated pathways. Pharmacological inhibition of store-operated calcium entry (SOCE) using the Orai1 inhibitor Synta66 suppressed IFN-γ-induced PD-L1 expression in a dose-dependent manner. Consistently, knockdown of Orai1 or STIM1 attenuated PD-L1 induction under IFN-γ stimulation, while basal expression remained unchanged. Inhibition of CaMK2 and CaMKK2 also reduced PD-L1 expression, indicating involvement of calmodulin-dependent kinase pathways. Functionally, Orai1 or STIM1 knockdown enhanced CD8⁺ T cell-mediated suppression of OSCC cell proliferation. Collectively, these results demonstrate that SOCE-mediated calcium signaling and downstream kinases regulate IFN-γ-induced PD-L1 expression and suggest that targeting SOCE components could represent a novel therapeutic approach to overcoming tumor immune evasion in OSCC. (132 words).</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100063"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Task-related attentional processes are distinctly modulated by respiration and RR interval variability.","authors":"Nozomu H Nakamura, Kohzoh Yoshino, Masaki Fukunaga","doi":"10.1016/j.jphyss.2025.100053","DOIUrl":"10.1016/j.jphyss.2025.100053","url":null,"abstract":"<p><p>Changes in reaction times (RTs) during attentional processing may be associated with the state of breathing. Although breathing and cardiac activity interact, the functional importance of the cardiorespiratory system for modulating attentional processing remains unclear. To determine the involvement of respiration and RR interval (RRI) variability in successful task performance, thirty-six healthy participants performed a short-term memory task. For RTs limited to correct responses, increases were observed under two conditions: i) when inspiratory onset (or exhalation-to-inhalation transition) occurred and ii) when RRI velocity increased during retrieval. Importantly, multilevel model analysis revealed that the timing of inspiratory onset and the increase in RRI velocity were temporally mismatched, suggesting that at least two independent mechanisms may prolong RT. These findings contribute to a better understanding of how respiration and RRI variability may be functionally differentiated and how each could be linked to attentional processes that influence performance.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100053"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic blackout in dynamic apnea: A case report.","authors":"Eric Mulder, Isak Löfquist, Felix Schagatay, Arne Sieber, Erika Schagatay","doi":"10.1016/j.jphyss.2026.100060","DOIUrl":"10.1016/j.jphyss.2026.100060","url":null,"abstract":"<p><p>Blackout (BO) in breath-hold diving is attributed to cerebral hypoxia, yet direct observations are rare. We continuously recorded arterial oxygen saturation (SpO₂) and heart rate (HR) in 11 trained freedivers (5 females) performing two dynamic apneas (75 m, 100 m) using a waterproof forehead oximeter. One diver experienced BO at the end of a 100 m dive (SpO₂ 51 %), recovering within 5 s. Group SpO₂ fell from 98 ± 1 % to 77 ± 9 % (75 m) and 68 ± 9 % (100 m; range 51-83 %), while mean HR declined from 83 ± 12 to 43 ± 8 and 40 ± 4bpm, respectively. No arrhythmias were detected. Within-diver SpO₂ nadirs were consistent between distances (r = 0.93), whereas HR nadirs were not (r = 0.40). This case confirms BO can occur at SpO₂ values around 50 %, even in the absence of arrhythmia. The BO diver consistently showed the lowest SpO₂, indicating profound hypoxemia as the most likely contributing factor. Findings support individualized risk screening based on early desaturation patterns in submaximal dives.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100060"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT3-dependent enhancement of apelinergic signaling mediates the cardioprotective effects of late-life high-intensity interval training.","authors":"Qiaowei Li, Yanmei Song, Qin Liu, Zhong Lin, Wenwen Lin, Feng Huang, Pengli Zhu","doi":"10.1016/j.jphyss.2026.100061","DOIUrl":"10.1016/j.jphyss.2026.100061","url":null,"abstract":"<p><strong>Background: </strong>Deficiency in apelinergic signaling (APJ/Apelin) has been shown to accelerate cardiac aging. Given our observation that high-intensity interval training (HIIT) upregulates APJ and Apelin in aged mouse hearts, this study aimed to investigate whether apelinergic signaling mediates the cardioprotective effects of exercise.</p><p><strong>Methods: </strong>Naturally aged (20-month-old) C57BL/6 mice were subjected to an 8-week HIIT regimen. To elucidate the role of APJ in HIIT-induced cardiac adaptions, mice were randomly assigned to one of three groups: HIIT with cardiomyocyte-specific APJ knockdown via adeno-associated virus, HIIT with an empty vector, and a sedentary control group. Senescent cardiomyocytes were employed to assess the impact of Apelin-13 and SIRT3 modulation on mitochondrial function. Additionally, a pharmacological study was conducted in aged mice using the APJ agonist AMG986, with or without the SIRT3 inhibitor 3TYP, to evaluate its therapeutic potential.</p><p><strong>Results: </strong>In aged mice, HIIT elevated myocardial APJ expression, resulting in improved cardiac function, reduced fibrosis and senescence, and preserved mitochondrial structure. Disruption of APJ/Apelin signaling pathway blunted these benefits, particularly impairing mitochondrial biogenesis, motility, mitophagy, and energy metabolism. In vitro, SIRT3 deficiency abolished Apelin-13-induced enhancements in mitochondrial membrane potential, respiratory capacity and morphology. In vivo, pharmacological activation of APJ reproduced key anti-aging cardiac effects, which were negated by SIRT3 inhibition.</p><p><strong>Conclusions: </strong>These findings suggested that HIIT exerted cardioprotective effects, at least in part, by enhancing apelinergic signaling and potentially modulating mitochondrial function through a SIRT3-dependent pathway. Targeting this pathway may provide potential therapeutic avenues for age-related cardiac dysfunction.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100061"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward the promotion of \"One Health\" - part I: How do humans work to live together with humans, other organisms, and xenobiotics on Earth?","authors":"Yumiko Imai, Shunsuke Kimura, Satoshi Kitajima, Norihiro Sadato, Ryosuke Chiba, Hiroshi Hibino, Satomi Adachi-Akahane","doi":"10.1016/j.jphyss.2025.100050","DOIUrl":"10.1016/j.jphyss.2025.100050","url":null,"abstract":"<p><p>Thirty years from now, society will be transformed by dramatic advances in digital transformation, life infrastructure, and personalized medicine. People will communicate seamlessly in virtual spaces, and older adults will enjoy more fulfilling lives. Nevertheless, increasingly complex lifestyles will place immense pressure on ecosystems, affecting the environment and organisms and leading to serious health challenges. To address these issues, the Japanese Association of Anatomists, the Physiological Society of Japan (PSJ), and the Japanese Pharmacological Society have launched a collaborative initiative on \"One Health\". This framework aims to integrate the protection of flora and fauna with the health of humans, animals, and the planet, extending even to outer space. In the symposium held at 2025 APPW congress cohosted by PSJ, experts from multiple disciplines discussed how humans can coexist with microbes, xenobiotics, humans, and robots on Earth, fostering a sustainable and resilient future. This article summarizes this One Health symposium.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100050"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12681810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of purinergic activation and TRPC3 channels in the Frank-Starling mechanism.","authors":"Yumiko Chiba, Keiko Kaihara, Gentaro Iribe","doi":"10.1016/j.jphyss.2025.100052","DOIUrl":"10.1016/j.jphyss.2025.100052","url":null,"abstract":"<p><p>TRPC3 channels are involved in the physiological and pathological myocardial responses to mechanical loads. However, the involvement of TRPC3 in the response to acute stretch, that is, the Frank-Starling mechanism, has not been comprehensively elucidated. To elucidate this, we analyzed the response to stretch in isolated mouse ventricular cardiomyocytes. Our analysis revealed that TRPC3-deficient cells exhibited significantly lower cellular end-systolic elastance, an index of contractility, than wild-type cells owing to the absence of acute stretch-induced reactive oxygen species (ROS) production. Subsequently, we demonstrated that ATP released from pannexin-1 during stretch activates the TRPC3-NOX2 complex via P2Y signaling, thereby increasing ROS production. The results of this study show that TRPC3 plays a role in the Frank-Starling mechanism by mediating the mechanotransduction pathway of stretch-induced ROS production, which is a novel physiological role for TRPC3 in the heart.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100052"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of local skeletal muscle cooling prior to acute exercise and endurance training on mitochondrial adaptation in mice.","authors":"Ryotaro Kano, Tatsuya Kusano, Taichi Ando, Reo Takeda, Ryui Natsuyama, Ryo Takagi, David C Poole, Yutaka Kano, Daisuke Hoshino","doi":"10.1016/j.jphyss.2026.100059","DOIUrl":"10.1016/j.jphyss.2026.100059","url":null,"abstract":"<p><p>While post-exercise cooling is known to enhance skeletal muscle adaptations, the effects of pre-exercise cooling remain unclear. This study investigated whether local muscle cooling immediately before exercise augments training-induced mitochondrial biogenesis in male C57BL/6 mice. Pre-exercise cooling involved 6 cycles of 6 min at 13°C followed by 4 min at 35°C on one hindlimb for 60 min before treadmill running. Acutely, this pre-cooling protocol increased exercise-induced PGC-1α mRNA expression by ∼13 % (p < 0.05) compared to exercise alone; this effect was abolished when cooling and exercise were separated by 3 h. Chronically, over 4 weeks, combined pre-cooling and exercise training significantly enhanced mitochondrial enzyme activities: citrate synthase (both main effects) and β-hydroxyacyl-CoA dehydrogenase (+23.9 % compared with exercise alone). However, mitochondrial structural protein levels remained unchanged. These results indicate that pre-exercise cooling promotes mitochondrial enzymatic adaptations in skeletal muscle, potentially offering a practical strategy to optimize the outcomes of endurance training.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100059"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of the association between blood glucose homeostasis and social hierarchy among co-housed mice by diet and amygdala activities.","authors":"Rikako Ukichi, Yukari Takahashi, Momoyo Ibukuro, Yae K Sugimura, Keiichiro Matoba, Rimei Nishimura, Fusao Kato","doi":"10.1016/j.jphyss.2026.100058","DOIUrl":"10.1016/j.jphyss.2026.100058","url":null,"abstract":"<p><p>Recent clinical studies suggest that individual psychosocial traits play a significant role in the onset and progression of diabetes. To examine whether glucose homeostasis depends on the social rank of individual mice, we analyzed the effects of dietary fat content on the hierarchy formed among co-housed mice and evaluated how perturbing rank by inhibiting amygdala neuronal activity influences glucose regulation. Social rank among four co-housed mice was assessed using the tube test. Switching to a high-fat diet altered blood glucose homeostasis, particularly by affecting rapid responses, and disrupted the established hierarchy, with the degree of disruption varying according to each mouse's rank. In contrast, chemogenetic inhibition of neuronal activities in the basolateral amygdala and surrounding area in the lowest-ranking mice modified both glucose homeostasis and its association with social rank. These findings provide mechanistic insight into the interaction between glucose regulation and psychosocial status.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100058"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian feeding promotion by Ninjin'yoeito counteracts frailty in aged mice.","authors":"Lei Wang, Yermek Rakhat, Masanori Nakata, Katsuya Dezaki, Hitoshi Kuwata, Boyang Zhang, Wanxin Han, Seiya Banno, Chikara Abe, Noboru Ogiso, Takashi Sakurai, Shin Tsunekawa, Daisuke Yabe, Yusaku Iwasaki, Yutaka Seino, Toshihiko Yada","doi":"10.1016/j.jphyss.2026.100062","DOIUrl":"10.1016/j.jphyss.2026.100062","url":null,"abstract":"<p><p>Frailty in aging is a major health challenge, requiring solution. Older people with frailty often exhibit malnutrition and dysregulated feeding. Feeding behavior displays circadian rhythm, while aging and frailty involve rhythm disorders, suggesting possible role of circadian feeding in frailty and treatment. Herbal medicine, Ninjin'yoeito (NYT), reportedly ameliorates frail symptoms. The present study explored impacts of NYT on circadian feeding and psychological/physical functions in aged mice. Here, we report that oral NYT independent of administration timing increases food intake specifically in 18:00-20:00, the pre-active phase, in aged and young mice, an effect mimicked by Chenpi and hesperidin. NYT altered appetite-regulating hormones and neuropeptides in pre-active phase. Repeated NYT administration restored anti-anxiety behavior, memory, and grip strength that declined in aged mice. These effects were blocked by food deprivation and pair-fed to control selectively in 18:00-20:00. These results reveal pre-active phase feeding promotion as a novel avenue to intervene aging-related frailty.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100062"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The intake of monosodium aspartate attenuates aggression induced by post-weaning social isolation in an ADHD rat model.","authors":"Yu Nishimura, Dewi Mustika, Shinya Ueno, Shiori Tominaga, Mariko Shindo, Naoki Tajiri, Cha-Gyun Jung, Hideki Hida","doi":"10.1016/j.jphyss.2026.100056","DOIUrl":"10.1016/j.jphyss.2026.100056","url":null,"abstract":"<p><p>We investigated whether monosodium aspartate (MSA), an umami compound structurally analogous to monosodium glutamate (MSG), influences aggressive behavior in a rat model of attention-deficit/hyperactivity disorder. Spontaneously hypertensive rats (SHR/Izm) were subjected to post-weaning social isolation and assessed using the resident-intruder paradigm. MSA ingestion significantly reduced aggression, particularly the frequency and duration of attacks, while the open field test showed no differences in anxiety-like behavior. c-Fos immunohistochemistry revealed increased neuronal activation in the intermediate nucleus of the solitary tract (iNTS) and decreased activation in the central amygdala (CeA) following MSA ingestion. This effect, along with the reduction in aggression, was abolished by vagotomy, suggesting gut-brain involvement. These findings indicate that MSA, like MSG, can reduce aggression via the gut-brain axis, implicating the vagus nerve, iNTS and CeA as key mediators. This highlights that the modulation of aggression by ingested amino acids is a broader effect acting through shared mechanisms.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100056"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}