{"title":"Effects of systemic ventricular assist combined with fenestration in failing Fontan: A theoretical analysis.","authors":"Shuji Shimizu, Yasuhiro Kotani, Naohiro Horio, Eiri Kisamori, Yoshinori Miyahara, Koji Uemura, Toshiaki Shishido, Shingo Kasahara","doi":"10.1016/j.jphyss.2026.100065","DOIUrl":"10.1016/j.jphyss.2026.100065","url":null,"abstract":"<p><p>Biventricular assist for failing Fontan circulation remains challenging. Because fenestration effectively reduces stressed blood volume and central venous pressure in Fontan patients with increased pulmonary vascular resistance (PVR), systemic ventricular assist device (VAD) combined with fenestration may improve hemodynamics in failing Fontan patients with increased PVR who would require biventricular assist. To validate this hypothesis, we performed a computational hemodynamic simulation of the failing Fontan circulation using a lumped parameter model. We compared hemodynamic variables between the models with and without fenestration while the PVR index was increased sequentially from 3.01 to 6.81 Wood Units m<sup>2</sup>. Following VAD initiation and stressed blood volume reduction, central venous pressure was maintained at a lower level in the fenestration models. This positive effect was greater in the model with larger fenestration diameter. However, excessive fenestration caused significant desaturation. In failing Fontan circulation with elevated PVR, systemic VAD combined with fenestration significantly improved hemodynamics.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100065"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197856","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}
Alamgir Hossain, Aya Yamamura, Rie Takahashi, Takashi Iezaki, Hisaki Hayashi, Hiroyuki Hirano, Hiroyuki Osada, Kazuo Umezawa, Motohiko Sato
{"title":"Identification of a small molecule that targets activator of G-protein signaling 8.","authors":"Alamgir Hossain, Aya Yamamura, Rie Takahashi, Takashi Iezaki, Hisaki Hayashi, Hiroyuki Hirano, Hiroyuki Osada, Kazuo Umezawa, Motohiko Sato","doi":"10.1016/j.jphyss.2026.100064","DOIUrl":"10.1016/j.jphyss.2026.100064","url":null,"abstract":"<p><p>Activator of G-protein signaling 8 (AGS8), also known as fibronectin type III domain containing 1 (FNDC1), is an accessory protein for heterotrimeric G-proteins involved in various cellular processes. The interaction between AGS8 and Gβγ subunit is a critical step in AGS8-mediated signaling, and a peptide that disrupts this interaction inhibited angiogenic events. To explore the broader potential of AGS8 biology, we investigated small molecules that block the AGS8-Gβγ interaction. Using a yeast-based system, in which cell growth depends on AGS8-mediated activation of G-protein pathway, we screened compounds from the RIKEN NPDepo library and identified one compound that effectively inhibited the formation of the AGS8-Gβγ complex. Consistent with the effects observed in AGS8 knockdown or peptide-treated cells, this compound attenuated VEGF-induced phosphorylation of signaling molecules and inhibited tube formation and migration of HUVECs. These data demonstrate the potential of the AGS8 inhibitor as a research tool and a therapeutic application.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100064"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157481","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":"EP4 stimulation promotes cell adhesion and migration via IL-6 signaling in oral squamous cell carcinoma.","authors":"Wakana Fukae, Soichiro Ishikawa, Yu Iida, Akane Nagasako, Michiko Endo, Chihiro Hayashi, Kagemichi Nagao, Sneri Oguri, Takayuki Fujita, Utako Yokoyama, Kenji Mitsudo, Yoshihiro Ishikawa, Masanari Umemura","doi":"10.1016/j.jphyss.2026.100057","DOIUrl":"10.1016/j.jphyss.2026.100057","url":null,"abstract":"<p><p>Oral squamous cell carcinoma cell (OSCC) comprises malignant neoplasms arising within the oral cavity. Early-stage detection is associated with favorable prognosis, whereas progression to advanced stages with lymph node metastasis significantly worsens outcomes. We previously reported that the prostaglandin E₂ (PGE₂) receptor EP4 regulates OSCC migration. RNA sequencing reanalysis suggested that EP4 stimulation is strongly associated with cell migration and adhesion, with interleukin-6 (IL-6) emerging as a central mediator of these processes. In OSCC cells, ONO-AE1-437 (EP4 agonist) increased IL-6 mRNA expression and protein secretion. EP4-overexpressing cells showed increased IL-6 expression without stimulation, further enhanced by ONO-AE1-437 or PGE₂. xCELLigence demonstrated that PGE₂ promoted cell adhesion, which was suppressed by ONO-AE3-208 (EP4 antagonist) and Tocilizumab (IL-6 inhibitor). Scratch and transwell assays revealed enhanced migration under PGE₂ and ONO-AE1-437, blocked by IL-6 inhibition. These results suggest that EP4 promotes cell adhesion and migration through IL-6 in OSCC cells. (147 words).</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100057"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12859506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029986","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}
Pauline Doussineau, Antoine Mariani, Laurent Reale, Chantal Verkindt, Florian Chouchou
{"title":"Interaction between respiration and central motor control in autonomic cardiac regulation.","authors":"Pauline Doussineau, Antoine Mariani, Laurent Reale, Chantal Verkindt, Florian Chouchou","doi":"10.1016/j.jphyss.2025.100054","DOIUrl":"10.1016/j.jphyss.2025.100054","url":null,"abstract":"<p><p>Adaptations in cardiac autonomic regulation induced by physical training are central to the health benefits of exercise. We investigated the interaction between central motor command, breathing rate, and expiration timing during an isolated joint movement. Fifteen volunteers (30.9 ± 7.2 years; 8 women) performed twelve 3-min leg extension tasks in a seated position under three randomized conditions: movement type (active vs. passive), breathing pattern (spontaneous, 12 or 6 cycles/min), and expiration timing (during extension vs. return). RR intervals and their variability were analyzed. Voluntary motor control reduced indices of autonomic and parasympathetic regulation (p < 0.05), whereas slow-paced breathing enhanced them. However, motor control exerted a dominant influence over cardiac autonomic regulation (p < 0.001), regardless of breathing rate. Expiration during the return phase was associated with greater parasympathetic activity (p < 0.05). These results highlight the central role of motor command in autonomic modulation and suggest that emphasizing expiration during recovery may help preserve parasympathetic regulation.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100054"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966277","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 coiled-coil domain of myosin-11 as a potential biomarker to detect patients with atherosclerotic cardiovascular disease risk.","authors":"Lisa Takahashi, Hirofumi Tomiyama, Hiroki Kobori, Yuko Hidaka, Shunichiro Orihara, Keiji Uchida, Kazuhiro Satomi, Masataka Taguri, Taishiro Chikamori, Utako Yokoyama","doi":"10.1016/j.jphyss.2026.100055","DOIUrl":"10.1016/j.jphyss.2026.100055","url":null,"abstract":"<p><p>Atherosclerosis leads to severe clinical complications, and biomarkers for asymptomatic atherosclerosis are desired. Plasma levels of myosin-11 have been reported to increase in patients with symptomatic atherosclerosis. To investigate the association between circulating myosin-11 levels and atherosclerotic cardiovascular disease (ASCVD) risk in patients without symptomatic atherosclerosis, this study recruited 161 participants: 80 patients with ASCVD risk, 50 patients with ischemic heart disease (IHD), and 31 control participants (Controls). We developed an ELISA that consists of rat monoclonal antibodies specific for the coiled-coil domain of myosin-11. Myosin-11 levels were highest in the IHD group, followed by the ASCVD risk group. The area under the receiver-operating characteristic curve of myosin-11 was 0.980 for IHD versus Controls and 0.874 for ASCVD risk versus Controls. The association between myosin-11 levels and hypertension remained significant after multivariate logistic regression analysis. Myosin-11 levels may be a biomarker for stratification of asymptomatic individuals with ASCVD risk.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100055"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985067","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":"Activation of aortic baroreceptors depresses the somato-lumbar sympathetic reflex, reducing hindlimb muscle contractile force.","authors":"Nobuhiro Watanabe, Kotaro Takeno, Naoko H Tomioka, Masamichi Moriya, Hiroshi Nishimune, Harumi Hotta","doi":"10.1016/j.jphyss.2025.100051","DOIUrl":"10.1016/j.jphyss.2025.100051","url":null,"abstract":"<p><p>We investigated whether the same sympathetic nerves innervate arteries and neuromuscular junctions and aortic baroreceptor stimulation reduces muscle force in rats. Histological analysis with fluorescent labeling revealed nicotinic acetylcholine receptors, motor nerves, adrenergic nerves, and arteries in gastrocnemius muscle tissue. Whole-mount preparations revealed a potential extension of adrenergic nerves around an artery connected to the neuromuscular junction. Physiological analysis under anesthesia was conducted to examine the effects of baroreceptor activation on muscle contractility and contraction-induced lumbar sympathetic reflex discharges following tetanic motor nerve stimulation. Intravenous phenylephrine injection increased mean arterial pressure to ∼150 mmHg and reduced both tetanic force and sympathetic reflex discharges when the aortic depressor nerves were intact. Bilateral aortic nerve denervation nearly abolished these effects. These findings indicate that aortic baroreceptor afferent signaling decreases hindlimb muscle contractility, most likely by inhibiting the contraction-induced sympathetic reflex. Sympathetic nerves distributed to arteries and neuromuscular junctions may underlie this modulation.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"76 1","pages":"100051"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634686","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":"LAMC1 aggravates diabetic retinopathy through PI3K/AKT signaling-regulated epithelial-mesenchymal transition in retinal pigment epithelial cells.","authors":"Lei Liu, Yanlin Gao, Shiqi Yao","doi":"10.1016/j.jphyss.2025.100045","DOIUrl":"10.1016/j.jphyss.2025.100045","url":null,"abstract":"<p><p>Diabetic retinopathy (DR), a leading cause of adult blindness, with LAMC1-mediated epithelial-mesenchymal transition (EMT) playing a key role. By analyzing DR-related microarray datasets (GSE60436/GSE102485) from GEO, we identified 685 differentially expressed genes (570 downregulated, 115 upregulated). Functional and WGCNA analyses linked these to PI3K/Akt signaling, revealing 11 diagnostic hub genes, including LAMC1. Western blot analysis confirmed that LAMC1 significantly upregulated in high glucose (HG)-treated ARPE-19 cells and diabetic mouse retinas. In vitro and in vivo experiments confirmed that LAMC1 promotes EMT in retinal pigment epithelial (RPE) cells via PI3K/Akt activation, enhancing migration and invasion. Conversely, LAMC1 knockdown alleviated retinal damage in diabetic mice. Our studies uncovered that LAMC1's role in DR progression through PI3K/Akt-driven EMT, suggesting its potential as a therapeutic target.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"75 3","pages":"100045"},"PeriodicalIF":3.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12550245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301680","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":"Podoplanin hetero-insufficiency mice with inflammation in the jejunum demonstrates a good animal model of congenital protein-losing enteropathy.","authors":"Toshio Ohhashi, Nagaharu Tsukiji, Moyuru Hayashi, Tomomi Watanabe-Asaka, Mieko Takasaka, Daisuke Maejima, Katsue Suzuki-Inoue, Yoshiko Kawai","doi":"10.1016/j.jphyss.2025.100031","DOIUrl":"10.1016/j.jphyss.2025.100031","url":null,"abstract":"<p><p>We have identified the Podoplanin expression in rat jejunal villi. We aimed to investigate the relationship between the Podoplanin expression in jejunal villi and the pathogenesis of congenital protein-losing enteropathy (PLE), using the Podoplanin heterozygous knock-out (Pdpn-het KO) mice and aspirin-induced inflammation of the jejunum. In the Pdpn-het KO mice the reticular and complexes distribution of Podoplanin was observed in the jejunal villi, resulting in be swollen of lamina propria. To confirm the abnormal distribution of small lymph vessels in the jejunal villi, the LYVE-1 immunohistochemical expression was investigated. The expression of Podoplanin and LYVE-1 in the jejunum of the Pdpn-het KO mice exhibited a distinct pattern. The intravenous administration of Evans blue dye appeared quickly into the mesenteric lymph vessels and lymph nodes in the wild-type but not observed in Pdpn-het KO mice. In the Pdpn-het KO mice, aspirin-induced jejunal inflammation produced a significant leakage of the intravenous administration of FITC-albumin into the jejunal lumen. The hypoalbuminemia in the blood and the marked distribution of FITC-albumin in the jejunal villi were also observed in the mice. In conclusion, we proposed that Pdpn-het KO mice with jejunal inflammation demonstrates a good animal model of the congenital PLE.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"75 3","pages":"100031"},"PeriodicalIF":3.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753647","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":"Incompleteness of the circle of Willis affects sleep quality, cognitive function and inflammation in patients with primary hypertension.","authors":"Ying Feng, Xueqi Yang, Yang Song, Yu Zhang, Tianning Zhang, Chenglong Yu","doi":"10.1016/j.jphyss.2025.100043","DOIUrl":"10.1016/j.jphyss.2025.100043","url":null,"abstract":"<p><p>To investigate whether incomplete Circle of Willis (Incomplete CoW) affects neuropsychological outcomes in patients with primary hypertension, a cross-sectional study was conducted involving 150 patients diagnosed with primary hypertension, a population at increased risk for neurovascular compromise. Magnetic Resonance Angiography was used to classify patients into two groups: Complete CoW (n = 41) and Incomplete CoW (n = 85). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and cognitive function was evaluated using the Mini-Mental State Examination (MMSE). PSQI scores were significantly higher in the Incomplete CoW group compared to the Complete CoW group, indicating poorer sleep quality in patients with an Incomplete CoW. A significant negative correlation was found between PSQI and MMSE scores in the Incomplete CoW group, linking poor sleep quality with cognitive impairment. These findings suggest that the incompleteness of the CoW may contribute to neuropsychological impairments in patients with hypertension, potentially mediated by enhanced inflammatory responses. DATA AVAILABILITY: The data used to support the findings of this study are available from the corresponding author upon request.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"75 3","pages":"100043"},"PeriodicalIF":3.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030125","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":"Estradiol enhances thermoregulation induced by ostruthin, a TREK channel agonist, in ovariectomized rats.","authors":"Yuki Uchida, Shotaro Kamijo, Yuki Samejima, Hiroshi Onimaru, Masahiro Hosonuma, Hikaru Isobe, Keiko Ikeda, Motoyasu Honma, Yuri Masaoka, Masahiko Izumizaki","doi":"10.1016/j.jphyss.2025.100044","DOIUrl":"10.1016/j.jphyss.2025.100044","url":null,"abstract":"<p><p>Menopausal women frequently report contradictory thermoregulatory symptoms (hot flashes and chills), believed to result from declining estradiol (E₂) levels; however, mechanisms remain unclear. TWIK-related (TREK) potassium channels function as cold receptors. Although E₂ enhances TREK1 activity in vitro, its effect on TREK-mediated thermoregulation has not been investigated in vivo. This study investigated whether E₂ facilitated TREK-mediated thermoregulation in ovariectomized rats using ostruthin, a TREK agonist. Rats were ovariectomized and implanted with silastic tubes with or without E₂, followed by ostruthin or vehicle injection. We measured thermoregulatory parameters, plasma hormones (triiodothyronine and thyroxine), and mRNA expression of cold receptors in dorsal root ganglia. Ventral root responses were examined in vitro. Ostruthin increased body temperature in E₂(+) versus E₂(-) groups, with increased triiodothyronine and upregulation of Trek1, Vgf, and Nos1. Ostruthin enhanced ventral root responses. These findings demonstrate that E₂ potentiates TREK-mediated thermoregulation through enhanced cold sensing, providing insights into menopausal disorders.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"75 3","pages":"100044"},"PeriodicalIF":3.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181934","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}