Pub Date : 2026-02-01DOI: 10.1016/j.job.2026.100747
Yixin Hu , Teng Xu , Chenfei Wang , Guijuan Feng
Background
Radiation-induced salivary gland dysfunction (RSGD) is a common complication of radiotherapy in patients with head and neck cancers that leads to xerostomia and related oral complications. It reduces treatment tolerance and quality of life, while current clinical interventions only alleviate superficial symptoms and fail to restore salivary gland function. This highlights the necessity to explore the pathogenesis of RSGD and to identify targets; existing studies have focused on DNA damage, oxidative stress, and fibrosis, but lack insights into emerging mechanisms such as ferroptosis, and therapies require improvement.
Conclusions
Based on models of radiation-induced salivary gland injury, this review had two core tasks: 1) to systematically explore multi-dimensional injury mechanisms, including existing and latest findings, and 2) to summarize current RSGD-related clinical drug regimens and stem cell/exosome-mediated therapies. The aims were to clarify core molecular mechanisms and potential targets, provide theoretical/practical references for novel effective therapies, overcome limitations in symptomatic treatment, and provide insights into how to improve outcomes and quality of life for patients with RSGD.
{"title":"Study on the mechanism of radioactive salivary gland injury: a relatively comprehensive statement","authors":"Yixin Hu , Teng Xu , Chenfei Wang , Guijuan Feng","doi":"10.1016/j.job.2026.100747","DOIUrl":"10.1016/j.job.2026.100747","url":null,"abstract":"<div><h3>Background</h3><div>Radiation-induced salivary gland dysfunction (RSGD) is a common complication of radiotherapy in patients with head and neck cancers that leads to xerostomia and related oral complications. It reduces treatment tolerance and quality of life, while current clinical interventions only alleviate superficial symptoms and fail to restore salivary gland function. This highlights the necessity to explore the pathogenesis of RSGD and to identify targets; existing studies have focused on DNA damage, oxidative stress, and fibrosis, but lack insights into emerging mechanisms such as ferroptosis, and therapies require improvement.</div></div><div><h3>Conclusions</h3><div>Based on models of radiation-induced salivary gland injury, this review had two core tasks: 1) to systematically explore multi-dimensional injury mechanisms, including existing and latest findings, and 2) to summarize current RSGD-related clinical drug regimens and stem cell/exosome-mediated therapies. The aims were to clarify core molecular mechanisms and potential targets, provide theoretical/practical references for novel effective therapies, overcome limitations in symptomatic treatment, and provide insights into how to improve outcomes and quality of life for patients with RSGD.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100747"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.job.2026.100749
Yi-Ying Hsieh , Chun-Jung Lin , Chia-Li Chi , Kuan-Yu Lin
Objectives
In this study, the effect of different rice-flour mixtures,used to modify steamed-bread texture, on swallowing-related muscle activity in older people, was explored. The objective was to identify the texture associated with reduced swallowing-related muscular activation accompanied by reduced bread hardness.
Methods
Sixty-eight community-dwelling people aged ≥65 years were recruited. Swallowing ability was assessed using the eating assessment tool 10 (EAT-10) swallowing screening tool, and each participant consumed 5 g of steamed bread containing 0 %, 10 %, 20 %, or 30 % rice flour in a randomized order. Suprahyoid muscle activity during swallowing was recorded using surface electromyography (sEMG), and peak swallowing-related EMG amplitude, extracted from the swallowing-related burst, was analyzed.
Results
Bread containing 20 % rice flour had the lowest hardness (199 × 103 N/m2) and required the least suprahyoid muscle activation (F = 4.26, p = 0.007). Regression analysis confirmed that rice-flour percentage was significantly associated with peak swallowing-related EMG amplitude (β = 0.41, p = 0.01; adjusted R2 = 0.717). Among participants with an EAT-10 score ≥3, the Wilcoxon signed-rank test indicated a significant reduction in peak swallowing-related EMG amplitude when consuming 20 % rice-flour bread (p = 0.01).
Conclusions
A 20 % rice-flour substitution provided a favorable steamed-bread texture associated with reduced swallowing-related muscular activation in older people. This simple dietary modification may facilitate safer swallowing by lowering the demand for muscle activation.
目的：在本研究中，探讨不同的米粉混合物，用于改善馒头的质地，对老年人吞咽相关的肌肉活动的影响。目的是确定与吞咽相关的肌肉活动减少以及面包硬度降低有关的质地。方法招募68名≥65岁的社区居民。使用进食评估工具10 （EAT-10）吞咽筛选工具评估吞咽能力，每个参与者按随机顺序食用5 g含0%、10%、20%或30%米粉的馒头。使用表面肌电图（sEMG）记录吞咽过程中舌骨上肌的活动，并分析从吞咽相关爆发中提取的吞咽相关肌电振幅峰值。结果含米粉20%的面包硬度最低（199 × 103 N/m2），舌骨上肌激活最少（F = 4.26, p = 0.007）。回归分析证实，米粉含量与吞咽相关肌电波幅峰显著相关（β = 0.41, p = 0.01；调整后R2 = 0.717）。在EAT-10评分≥3的参与者中，Wilcoxon符号秩检验表明，当食用20%米粉面包时，吞咽相关肌电波峰显著降低（p = 0.01）。结论20%的米粉替代品提供了良好的馒头质地，并减少了老年人吞咽相关肌肉活动。这种简单的饮食调整可以通过降低对肌肉激活的需求来促进更安全的吞咽。
{"title":"Effect of differences in food texture on swallowing-related muscle activity in older people","authors":"Yi-Ying Hsieh , Chun-Jung Lin , Chia-Li Chi , Kuan-Yu Lin","doi":"10.1016/j.job.2026.100749","DOIUrl":"10.1016/j.job.2026.100749","url":null,"abstract":"<div><h3>Objectives</h3><div>In this study, the effect of different rice-flour mixtures,used to modify steamed-bread texture, on swallowing-related muscle activity in older people, was explored. The objective was to identify the texture associated with reduced swallowing-related muscular activation accompanied by reduced bread hardness.</div></div><div><h3>Methods</h3><div>Sixty-eight community-dwelling people aged ≥65 years were recruited. Swallowing ability was assessed using the eating assessment tool 10 (EAT-10) swallowing screening tool, and each participant consumed 5 g of steamed bread containing 0 %, 10 %, 20 %, or 30 % rice flour in a randomized order. Suprahyoid muscle activity during swallowing was recorded using surface electromyography (sEMG), and peak swallowing-related EMG amplitude, extracted from the swallowing-related burst, was analyzed.</div></div><div><h3>Results</h3><div>Bread containing 20 % rice flour had the lowest hardness (199 × 10<sup>3</sup> N/m<sup>2</sup>) and required the least suprahyoid muscle activation (F = 4.26, p = 0.007). Regression analysis confirmed that rice-flour percentage was significantly associated with peak swallowing-related EMG amplitude (β = 0.41, p = 0.01; adjusted R<sup>2</sup> = 0.717). Among participants with an EAT-10 score ≥3, the Wilcoxon signed-rank test indicated a significant reduction in peak swallowing-related EMG amplitude when consuming 20 % rice-flour bread (p = 0.01).</div></div><div><h3>Conclusions</h3><div>A 20 % rice-flour substitution provided a favorable steamed-bread texture associated with reduced swallowing-related muscular activation in older people. This simple dietary modification may facilitate safer swallowing by lowering the demand for muscle activation.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100749"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.job.2026.100743
Mayu Onishi , Akihiro Yamaguchi , Yuka Abe , Taro Sato , Miho Fujishima , Wado Akamatsu , Kazuyoshi Baba
Objectives
Sleep bruxism (SB) involves involuntary jaw movements during sleep and has been linked to impaired inhibitory regulation of brainstem circuits (particularly those involving GABAergic neurons). While previous studies using patch-clamp electrophysiology have demonstrated intrinsic hyperexcitability in neurons differentiated from SB patient-derived human induced pluripotent stem cells (hiPSCs), the low-throughput nature of this technique limits large-scale phenotypic screening. We aimed to establish a robust, high-throughput, multielectrode array (MEA)-based platform capable of quantitatively assessing electrophysiological phenotypes of SB-derived neurons.
Methods
hiPSCs from three patients with SB and three healthy controls were differentiated to become ventral brainstem-like neurons. Their neuronal composition was evaluated using immunocytochemistry for total neurons (TUBB3+) and GABAergic neurons (GAD1/2+). Spontaneous neuronal firing was assessed using MEA under steady-state conditions and immediately after medium change. Extracellular GABA levels were quantified via ELISA to indirectly assess GABAergic hyperexcitability.
Results
Differentiation efficiency to TUBB3+ or GAD1/2+ neurons did not differ among cell lines. Under steady-state conditions, the weighted mean firing rate (wMFR) did not differ between groups. The SB group showed significantly elevated extracellular GABA concentrations and a significant increase in wMFR immediately after medium change (GABA removal), suggesting that GABA hypersecretion concealed the underlying hyperexcitability of SB-derived neurons.
Conclusions
We developed a robust, high-throughput MEA platform that reliably quantifies SB-related electrophysiological phenotypes. Our findings indicate that SB-derived GABAergic neurons exhibit constitutive hyperexcitability and excessive GABA release, providing mechanistic insights and a scalable framework for therapeutic discovery.
{"title":"Modeling GABAergic hyperexcitability in sleep bruxism patient-derived brainstem neurons using a multielectrode array platform","authors":"Mayu Onishi , Akihiro Yamaguchi , Yuka Abe , Taro Sato , Miho Fujishima , Wado Akamatsu , Kazuyoshi Baba","doi":"10.1016/j.job.2026.100743","DOIUrl":"10.1016/j.job.2026.100743","url":null,"abstract":"<div><h3>Objectives</h3><div>Sleep bruxism (SB) involves involuntary jaw movements during sleep and has been linked to impaired inhibitory regulation of brainstem circuits (particularly those involving GABAergic neurons). While previous studies using patch-clamp electrophysiology have demonstrated intrinsic hyperexcitability in neurons differentiated from SB patient-derived human induced pluripotent stem cells (hiPSCs), the low-throughput nature of this technique limits large-scale phenotypic screening. We aimed to establish a robust, high-throughput, multielectrode array (MEA)-based platform capable of quantitatively assessing electrophysiological phenotypes of SB-derived neurons.</div></div><div><h3>Methods</h3><div>hiPSCs from three patients with SB and three healthy controls were differentiated to become ventral brainstem-like neurons. Their neuronal composition was evaluated using immunocytochemistry for total neurons (TUBB3<sup>+</sup>) and GABAergic neurons (GAD1/2<sup>+</sup>). Spontaneous neuronal firing was assessed using MEA under steady-state conditions and immediately after medium change. Extracellular GABA levels were quantified via ELISA to indirectly assess GABAergic hyperexcitability.</div></div><div><h3>Results</h3><div>Differentiation efficiency to TUBB3<sup>+</sup> or GAD1/2<sup>+</sup> neurons did not differ among cell lines. Under steady-state conditions, the weighted mean firing rate (wMFR) did not differ between groups. The SB group showed significantly elevated extracellular GABA concentrations and a significant increase in wMFR immediately after medium change (GABA removal), suggesting that GABA hypersecretion concealed the underlying hyperexcitability of SB-derived neurons.</div></div><div><h3>Conclusions</h3><div>We developed a robust, high-throughput MEA platform that reliably quantifies SB-related electrophysiological phenotypes. Our findings indicate that SB-derived GABAergic neurons exhibit constitutive hyperexcitability and excessive GABA release, providing mechanistic insights and a scalable framework for therapeutic discovery.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100743"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Remimazolam, a novel ultra-short-acting benzodiazepine anesthetic, provides rapid recovery with minimal circulatory depression, making it a promising agent for procedural sedation. However, differences in regulatory approvals and safety requirements across countries limit its clinical use. Therefore, its pharmacological properties and safety should be clarified in further studies. In this study, jugular vein-cannulated model mice were administered intravenous anesthetic, and the sedative effects of remimazolam were compared with those of midazolam and propofol.
Methods
Following jugular vein cannulation, each mouse was administered a single intravenous dose of remimazolam or midazolam, and changes in sedation levels were assessed using a sedation scale. In another test, continuous infusion of propofol or remimazolam was administered using a precise microflow pump and sedation scale scores, defensive reflexes, and vital signs were analyzed.
Results
The sedation scale score increased after a single administration of remimazolam or midazolam in a concentration-dependent manner, followed by gradual recovery, whereas continuous administration caused a gradual increase that stabilized over time. Continuous remimazolam administration (30 mg/kg/h) produced sedation comparable to that produced by propofol administration (120 mg/kg/h), although with much smaller decreases in heart and breathing rates. Defensive reflex reactivity in mice administered remimazolam exhibited a shorter time to reflex extinction than in those administered propofol, with repeated extinction and recovery cycles.
Conclusions
Our findings suggest that the jugular vein-cannulated mouse model is useful for evaluating time-dependent sedative effects. Continuous remimazolam administrationmaintained stable sedation with minimal vital depression and faster defensive reflex suppression than propofol administration.
{"title":"Evaluation of anesthetic effects of remimazolam using mouse model with jugular vein cannulation","authors":"Aoi Ikuse-Oshio , Yuki Azetsu , Aiko Hirayama , Akiko Karakawa , Masahiro Chatani , Akiko Nishimura , Rikuo Masuda , Masamichi Takami","doi":"10.1016/j.job.2026.100741","DOIUrl":"10.1016/j.job.2026.100741","url":null,"abstract":"<div><h3>Objective</h3><div>Remimazolam, a novel ultra-short-acting benzodiazepine anesthetic, provides rapid recovery with minimal circulatory depression, making it a promising agent for procedural sedation. However, differences in regulatory approvals and safety requirements across countries limit its clinical use. Therefore, its pharmacological properties and safety should be clarified in further studies. In this study, jugular vein-cannulated model mice were administered intravenous anesthetic, and the sedative effects of remimazolam were compared with those of midazolam and propofol.</div></div><div><h3>Methods</h3><div>Following jugular vein cannulation, each mouse was administered a single intravenous dose of remimazolam or midazolam, and changes in sedation levels were assessed using a sedation scale. In another test, continuous infusion of propofol or remimazolam was administered using a precise microflow pump and sedation scale scores, defensive reflexes, and vital signs were analyzed.</div></div><div><h3>Results</h3><div>The sedation scale score increased after a single administration of remimazolam or midazolam in a concentration-dependent manner, followed by gradual recovery, whereas continuous administration caused a gradual increase that stabilized over time. Continuous remimazolam administration (30 mg/kg/h) produced sedation comparable to that produced by propofol administration (120 mg/kg/h), although with much smaller decreases in heart and breathing rates. Defensive reflex reactivity in mice administered remimazolam exhibited a shorter time to reflex extinction than in those administered propofol, with repeated extinction and recovery cycles.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that the jugular vein-cannulated mouse model is useful for evaluating time-dependent sedative effects. Continuous remimazolam administrationmaintained stable sedation with minimal vital depression and faster defensive reflex suppression than propofol administration.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100741"},"PeriodicalIF":2.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The nose and mouth are the primary entry points for upper respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, the influence of different entry routes on viral spread remains unclear. Oral and nasal infection routes in terms of viral distribution and presence of inflammation were compared.
Methods
Syrian hamsters were inoculated with SARS-CoV-2 via three routes: nasal inoculation (NI), simulating conventional upper respiratory infection; lingual (supra-lingual) inoculation (LI), simulating exposure during speaking and eating; and sublingual inoculation (SI), simulating exposure to the salivary glands. After three days, the lungs, submandibular glands, nasal turbinates, liver, and brain were examined histologically and immunohistochemically. To assess direct access to the lungs, India ink was administered via each route and analyzed after tissue clearing.
Results
NI resulted in infection in the nasal olfactory sensory epithelium of the nasal cavity and in the lungs. India ink studies suggest that the virus is likely to have infected the nasal mucosa first, followed by secondary infection of the lungs. LI resulted in marked infection of the submandibular glands with vascular involvement. In the LI and SI groups, no viral antigen was detected in the lungs; however, there was inflammation of the lungs, suggesting cytokine-mediated effects.
Conclusion
Different upper respiratory entry routes produced distinct pathological patterns. While nasal infection is well recognized, our findings indicate that salivary gland infection via SI may suggest an alternative pathway for systemic viral dissemination.
{"title":"Oral SARS-CoV-2 inoculation leads to distinct viral distribution compared to nasal inoculation in a Syrian hamster model","authors":"Nao Gojo , Yu Usami , Katsutoshi Hirose , Satoru Toyosawa , Shintaro Shichinohe , Tokiko Watanabe , Chikako Ono , Tsuyoshi Inoue , Takayoshi Sakai","doi":"10.1016/j.job.2026.100746","DOIUrl":"10.1016/j.job.2026.100746","url":null,"abstract":"<div><h3>Objectives</h3><div>The nose and mouth are the primary entry points for upper respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, the influence of different entry routes on viral spread remains unclear. Oral and nasal infection routes in terms of viral distribution and presence of inflammation were compared.</div></div><div><h3>Methods</h3><div>Syrian hamsters were inoculated with SARS-CoV-2 via three routes: nasal inoculation (NI), simulating conventional upper respiratory infection; lingual (supra-lingual) inoculation (LI), simulating exposure during speaking and eating; and sublingual inoculation (SI), simulating exposure to the salivary glands. After three days, the lungs, submandibular glands, nasal turbinates, liver, and brain were examined histologically and immunohistochemically. To assess direct access to the lungs, India ink was administered via each route and analyzed after tissue clearing.</div></div><div><h3>Results</h3><div>NI resulted in infection in the nasal olfactory sensory epithelium of the nasal cavity and in the lungs. India ink studies suggest that the virus is likely to have infected the nasal mucosa first, followed by secondary infection of the lungs. LI resulted in marked infection of the submandibular glands with vascular involvement. In the LI and SI groups, no viral antigen was detected in the lungs; however, there was inflammation of the lungs, suggesting cytokine-mediated effects.</div></div><div><h3>Conclusion</h3><div>Different upper respiratory entry routes produced distinct pathological patterns. While nasal infection is well recognized, our findings indicate that salivary gland infection via SI may suggest an alternative pathway for systemic viral dissemination.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100746"},"PeriodicalIF":2.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
While commensal microbiota are known to play essential roles in functional maturation of the innate immune system, the mechanisms by which microbial signals shape pulmonary immunity remain unclear. We performed single-cell RNA sequencing of lung immune cells from germ-free (GF) and conventional (CV) mice under normal physiological and LPS-induced septic conditions.
Methods
Lung immune cells were isolated from GF and CV mice exposed to normal or septic conditions. Single-cell RNA sequencing data were analyzed using standard pipelines with cell-type annotation and pathway profiling based on enrichment analyses.
Results
In GF mice, innate immune cell populations, including neutrophils, macrophages, and natural killer cells, exhibited an altered baseline transcriptional state characterized by reduced inflammatory readiness and a shift toward metabolic and stress-associated programs relative to these cell populations in CV mice. Neutrophils from GF mice exhibited a disrupted maturation trajectory with loss of transitional states and immature cell accumulation, suggesting that microbiota-derived cues are necessary to complete peripheral maturation and support a conserved systemic mechanism of microbiota-dependent innate immune differentiation. The lipopolysaccharide-responsive sub-cluster of macrophages exhibited high CCAAT enhancer-binding protein beta (Cebpb) expression in CV mice, which was linked to preferential engagement of inflammatory rather than homeostatic programs, whereas these macrophages in GF mice failed to induce Cebpb. During LPS-induced sepsis, lack of microbial priming results in blunted inflammatory responses and inadequate transcriptional network activation.
Conclusions
Commensal microbiota influence transcriptional activity and maturation of pulmonary innate immune cells under experimental conditions, thereby influencing susceptibility to LPS-induced lung injury. Targeting microbiota-guided immune training pathways may allow modulation of pulmonary host defenses.
{"title":"Microbiota-dependent transcriptional priming of lung innate immune cells in a mouse model of LPS-induced sepsis-associated lung injury","authors":"Kota Iioka , Hirobumi Morisaki , Tomoki Makiura , Haruka Fukamachi , Mie Kurosawa , Armelia Sari Widyarman , Ayako Sato , Mariko Kikuchi , Manami Hayashi , Hiroki Ishikawa , Masayuki Iyoda , Rikuo Masuda , Hirotaka Kuwata","doi":"10.1016/j.job.2026.100742","DOIUrl":"10.1016/j.job.2026.100742","url":null,"abstract":"<div><h3>Objectives</h3><div>While commensal microbiota are known to play essential roles in functional maturation of the innate immune system, the mechanisms by which microbial signals shape pulmonary immunity remain unclear. We performed single-cell RNA sequencing of lung immune cells from germ-free (GF) and conventional (CV) mice under normal physiological and LPS-induced septic conditions.</div></div><div><h3>Methods</h3><div>Lung immune cells were isolated from GF and CV mice exposed to normal or septic conditions. Single-cell RNA sequencing data were analyzed using standard pipelines with cell-type annotation and pathway profiling based on enrichment analyses.</div></div><div><h3>Results</h3><div>In GF mice, innate immune cell populations, including neutrophils, macrophages, and natural killer cells, exhibited an altered baseline transcriptional state characterized by reduced inflammatory readiness and a shift toward metabolic and stress-associated programs relative to these cell populations in CV mice. Neutrophils from GF mice exhibited a disrupted maturation trajectory with loss of transitional states and immature cell accumulation, suggesting that microbiota-derived cues are necessary to complete peripheral maturation and support a conserved systemic mechanism of microbiota-dependent innate immune differentiation. The lipopolysaccharide-responsive sub-cluster of macrophages exhibited high CCAAT enhancer-binding protein beta (<em>Cebpb</em>) expression in CV mice, which was linked to preferential engagement of inflammatory rather than homeostatic programs, whereas these macrophages in GF mice failed to induce <em>Cebpb</em>. During LPS-induced sepsis, lack of microbial priming results in blunted inflammatory responses and inadequate transcriptional network activation.</div></div><div><h3>Conclusions</h3><div>Commensal microbiota influence transcriptional activity and maturation of pulmonary innate immune cells under experimental conditions, thereby influencing susceptibility to LPS-induced lung injury. Targeting microbiota-guided immune training pathways may allow modulation of pulmonary host defenses.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100742"},"PeriodicalIF":2.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
After direct pulp capping with mineral trioxide aggregate (MTA), osteopontin (OPN) deposition occurs beneath the exposed pulp before the differentiation of odontoblast-like cells. This study aims to determine whether OPN is directly required for dentin bridge formation following direct pulp capping.
Methods
Pulp exposures were made on the occlusal surface of maxillary first molars of five to six week-old, wild-type (WT) and Opn knockout (KO) mice. The cavity was filled with MTA and then with glass ionomer cement. One to 28 days (PODs 1–28), specimens were subjected to immunohistochemistry for evaluating nestin, OPN, Ki67, dentin matrix protein (DMP)-1, F4/80, and CD206; and quantitative real-time polymerase-chain reaction was performed for evaluating nestin (Nes), dentin sialophosphoprotein (Dspp), Dmp-1, and Opn mRNA.
Results
In WT mice, OPN was deposited just beneath the exposed pulp after odontoblast degeneration on POD 3, followed by an increase in Nes mRNA expression and CD206 immunoreactivity on POD 5. Nestin-positive odontoblast-like cells aligned on POD 14, resulting in dentin bridge formation on POD 28. Conversely, the arrangement of nestin-positive odontoblast-like cells was disrupted in Opn KO mice, with decreased expression levels of Nes mRNA, Dspp mRNA, and CD206-immunoreactivity on PODs 3–7. Eventually, dentin bridge formation was suppressed, resulting in pulp necrosis on POD 28.
Conclusions
Following direct pulp capping with MTA, Opn KO mice exhibited impaired arrangement of nestin-positive odontoblast-like cells and failed to form a dentin bridge, indicating that OPN contributes remarkably to these responses.
{"title":"Osteopontin deficiency disturbs dentin bridge formation after direct pulp capping with mineral trioxide aggregate","authors":"Risa Ohshima , Angela Quispe-Salcedo , Hayato Ohshima , Nobuyuki Kawashima , Takashi Okiji , Yoshio Yahata","doi":"10.1016/j.job.2026.100740","DOIUrl":"10.1016/j.job.2026.100740","url":null,"abstract":"<div><h3>Objectives</h3><div>After direct pulp capping with mineral trioxide aggregate (MTA), osteopontin (OPN) deposition occurs beneath the exposed pulp before the differentiation of odontoblast-like cells. This study aims to determine whether OPN is directly required for dentin bridge formation following direct pulp capping.</div></div><div><h3>Methods</h3><div>Pulp exposures were made on the occlusal surface of maxillary first molars of five to six week-old, wild-type (WT) and <em>Opn</em> knockout (KO) mice. The cavity was filled with MTA and then with glass ionomer cement. One to 28 days (PODs 1–28), specimens were subjected to immunohistochemistry for evaluating nestin, OPN, Ki67, dentin matrix protein (DMP)-1, F4/80, and CD206; and quantitative real-time polymerase-chain reaction was performed for evaluating <em>nestin (Nes</em>), <em>dentin sialophosphoprotein</em> (<em>Dspp</em>), <em>Dmp-1</em>, <em>and Opn</em> mRNA.</div></div><div><h3>Results</h3><div>In WT mice, OPN was deposited just beneath the exposed pulp after odontoblast degeneration on POD 3, followed by an increase in <em>Nes</em> mRNA expression and CD206 immunoreactivity on POD 5. Nestin-positive odontoblast-like cells aligned on POD 14, resulting in dentin bridge formation on POD 28. Conversely, the arrangement of nestin-positive odontoblast-like cells was disrupted in <em>Opn</em> KO mice, with decreased expression levels of <em>Nes</em> mRNA, <em>Dspp</em> mRNA, and CD206-immunoreactivity on PODs 3–7. Eventually, dentin bridge formation was suppressed, resulting in pulp necrosis on POD 28.</div></div><div><h3>Conclusions</h3><div>Following direct pulp capping with MTA, <em>Opn</em> KO mice exhibited impaired arrangement of nestin-positive odontoblast-like cells and failed to form a dentin bridge, indicating that OPN contributes remarkably to these responses.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100740"},"PeriodicalIF":2.3,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salivary gland secretory function is impaired by tissue injury, but subsequently recovers if the damage is not severe. We previously reported that tissue injury can cause secretory granule loss and ectopic expression of claudins and stem cell markers including nestin in parotid acinar cells. Such alterations may indicate acinar cell dedifferentiation contributing to cell survival. We investigated transforming growth factor (TGF)-β superfamily member expression profiles and functions to identify tissue injury responsive signals.
Methods
Acinar cells were isolated from the rat parotid glands via extracellular matrix digestion with collagenase and hyaluronidase and cultured in the absence or presence of the Src kinase inhibitor PP1. TGF-β superfamily expression was determined by reverse transcription quantitative PCR (RT-qPCR). Acinar cells were then cultured with inhibitors of bone morphogenetic protein (BMP) or TGF-β. A Cell Counting Kit-8 was used to assess cell proliferation, and immunoblotting was used to examine the expression of cell adhesion molecules and the stem cell marker nestin.
Results
Increased BMP-2, BMP-6, and TGF-β1 expression was observed in primary culture of parotid acinar cells. Their expression decreased under Src inhibitor treatment. BMP-2/4 and TGF-β signaling inhibitors suppressed cell proliferation. These inhibitors also decreased claudin-4 and nestin expression, which was absent in intact acinar tissue, but present after cell isolation.
Conclusions
BMP-2 and TGF-β1 may contribute to tissue regeneration and protection by enhancing paracellular barrier function.
{"title":"Bone morphogenetic protein-2 and transforming growth factor-β1 regulate cell proliferation and ectopic claudin-4 expression in parotid acinar cells","authors":"Katsumasa Ueki, Megumi Yokoyama, Osamu Katsumata-Kato, Junko Fujita-Yoshigaki","doi":"10.1016/j.job.2026.100735","DOIUrl":"10.1016/j.job.2026.100735","url":null,"abstract":"<div><h3>Objectives</h3><div>Salivary gland secretory function is impaired by tissue injury, but subsequently recovers if the damage is not severe. We previously reported that tissue injury can cause secretory granule loss and ectopic expression of claudins and stem cell markers including nestin in parotid acinar cells. Such alterations may indicate acinar cell dedifferentiation contributing to cell survival. We investigated transforming growth factor (TGF)-β superfamily member expression profiles and functions to identify tissue injury responsive signals.</div></div><div><h3>Methods</h3><div>Acinar cells were isolated from the rat parotid glands via extracellular matrix digestion with collagenase and hyaluronidase and cultured in the absence or presence of the Src kinase inhibitor PP1. TGF-β superfamily expression was determined by reverse transcription quantitative PCR (RT-qPCR). Acinar cells were then cultured with inhibitors of bone morphogenetic protein (BMP) or TGF-β. A Cell Counting Kit-8 was used to assess cell proliferation, and immunoblotting was used to examine the expression of cell adhesion molecules and the stem cell marker nestin.</div></div><div><h3>Results</h3><div>Increased BMP-2, BMP-6, and TGF-β1 expression was observed in primary culture of parotid acinar cells. Their expression decreased under Src inhibitor treatment. BMP-2/4 and TGF-β signaling inhibitors suppressed cell proliferation. These inhibitors also decreased claudin-4 and nestin expression, which was absent in intact acinar tissue, but present after cell isolation.</div></div><div><h3>Conclusions</h3><div>BMP-2 and TGF-β1 may contribute to tissue regeneration and protection by enhancing paracellular barrier function.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100735"},"PeriodicalIF":2.3,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.job.2026.100733
Jose Francisco Rodríguez-Vázquez , Kenta Abe , Kazuma Morita , Yuki Yoshihashi , Masahito Yamamoto , Shin-ichi Abe
Objectives
The hyoid lesser horn (LH) forms a transient joint with the greater horn in human fetuses. The chondroglossus muscle attaches to the LH; however, its morphology remains unclear. We hypothesized that the muscles involved in LH accelerate joint formation.
Methods: We examined 34 human fetuses with crown-rump length of 39–230 mm.
Results
The LH joint was bilaterally absent in eight fetuses; the largest specimen “without” joints was 110 mm crown-rump length, whereas the smallest specimen “with” joints was 55 mm. The chondroglossus was identified as oblique muscle fibers attached to the LH medial aspect (23/34). The chondroglossus, Adjacent to the transverse lingual muscle (TLM), the chondroglossus ran supero-antero-medially to join the genioglossus. The TLM (21/34) and middle pharyngeal constrictor (pars chondropharyngica; 21/34) originated from the LH. The latter ran posteriorly from the LH medial to the hypoglossal nerve, whereas the middle constrictor arose largely from the greater horn. Notably, without LH attachment, the anterior margin of the mylohyoideus muscle (MPCM) was connected to the TLM using thick fascia wrapped around the LH. Therefore, LH disrupts the muscular ring surrounding the oropharynx.
Conclusions
The variation in joint formation timing (9–16 weeks gestational age) suggests that the chondroglossus, TLM, and MPCM development do not require joint movement. Alternatively, an elongated greater horn may provide joint-like space.
{"title":"Growing lesser horn of the hyoid in human fetuses with special references to muscles attaching to it","authors":"Jose Francisco Rodríguez-Vázquez , Kenta Abe , Kazuma Morita , Yuki Yoshihashi , Masahito Yamamoto , Shin-ichi Abe","doi":"10.1016/j.job.2026.100733","DOIUrl":"10.1016/j.job.2026.100733","url":null,"abstract":"<div><h3>Objectives</h3><div>The hyoid lesser horn (LH) forms a transient joint with the greater horn in human fetuses. The chondroglossus muscle attaches to the LH; however, its morphology remains unclear. We hypothesized that the muscles involved in LH accelerate joint formation.</div><div>Methods: We examined 34 human fetuses with crown-rump length of 39–230 mm.</div></div><div><h3>Results</h3><div>The LH joint was bilaterally absent in eight fetuses; the largest specimen “without” joints was 110 mm crown-rump length, whereas the smallest specimen “with” joints was 55 mm. The chondroglossus was identified as oblique muscle fibers attached to the LH medial aspect (23/34). The chondroglossus, Adjacent to the transverse lingual muscle (TLM), the chondroglossus ran supero-antero-medially to join the genioglossus. The TLM (21/34) and middle pharyngeal constrictor (pars chondropharyngica; 21/34) originated from the LH. The latter ran posteriorly from the LH medial to the hypoglossal nerve, whereas the middle constrictor arose largely from the greater horn. Notably, without LH attachment, the anterior margin of the mylohyoideus muscle (MPCM) was connected to the TLM using thick fascia wrapped around the LH. Therefore, LH disrupts the muscular ring surrounding the oropharynx.</div></div><div><h3>Conclusions</h3><div>The variation in joint formation timing (9–16 weeks gestational age) suggests that the chondroglossus, TLM, and MPCM development do not require joint movement. Alternatively, an elongated greater horn may provide joint-like space.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100733"},"PeriodicalIF":2.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to evaluate the effects of long-term administration of Ninjin'yoeito, a traditional Japanese Kampo medicine, on age-related salivary hypofunction in mice.
Methods
Male senescence-accelerated mice (SAMP1) were divided into two groups and fed either a control diet, or a diet containing 3 % Ninjin'yoeito extract for four months. Salivary gland function was assessed by measuring the flow rate after muscarinic stimulation of the submandibular glands perfused ex vivo. Additional analysis included histological and immunohistochemical evaluations, blood tests, and real-time PCR to investigate gland morphology, immune cell profiles, gene expression, and inflammation/aging markers.
Results
Long-term Ninjin'yoeito administration significantly increased salivary secretion after stimulation and decreased the number of vacuoles in acinar cells as compared to the controls. Ninjin'yoeito improved the plasma albumin levels and increased the lymphocyte ratio in the white blood cell count. Furthermore, real-time PCR revealed decreased levels of inflammatory cytokine and senescence-associated genes. No significant changes were detected in the expression or localization of the main salivary secretion-related channels, such as transmembrane protein 16A and aquaporin 5.
Conclusions
Ninjin'yoeito enhances salivary secretion from the submandibular glands of aged mice by improving nutritional status, modulating immune function, suppressing chronic inflammation, and attenuating cellular aging. These results suggest that Ninjin'yoeito has potential applications as a complementary therapy for age-related dry mouth.
{"title":"Ninjin'yoeito enhances saliva secretion in aged mice via nutritional, immune, anti-inflammatory, and anti-aging effects","authors":"Tomoki Kurakata, Yusuke Kondo, Akihiro Nakamura, Yui Hirata Obikane, Tomotaka Nodai, Takashi Munemasa, Taro Mukaibo, Ryuji Hosokawa, Chihiro Masaki","doi":"10.1016/j.job.2026.100739","DOIUrl":"10.1016/j.job.2026.100739","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to evaluate the effects of long-term administration of Ninjin'yoeito, a traditional Japanese Kampo medicine, on age-related salivary hypofunction in mice.</div></div><div><h3>Methods</h3><div>Male senescence-accelerated mice (SAMP1) were divided into two groups and fed either a control diet, or a diet containing 3 % Ninjin'yoeito extract for four months. Salivary gland function was assessed by measuring the flow rate after muscarinic stimulation of the submandibular glands perfused ex vivo. Additional analysis included histological and immunohistochemical evaluations, blood tests, and real-time PCR to investigate gland morphology, immune cell profiles, gene expression, and inflammation/aging markers.</div></div><div><h3>Results</h3><div>Long-term Ninjin'yoeito administration significantly increased salivary secretion after stimulation and decreased the number of vacuoles in acinar cells as compared to the controls. Ninjin'yoeito improved the plasma albumin levels and increased the lymphocyte ratio in the white blood cell count. Furthermore, real-time PCR revealed decreased levels of inflammatory cytokine and senescence-associated genes. No significant changes were detected in the expression or localization of the main salivary secretion-related channels, such as transmembrane protein 16A and aquaporin 5.</div></div><div><h3>Conclusions</h3><div>Ninjin'yoeito enhances salivary secretion from the submandibular glands of aged mice by improving nutritional status, modulating immune function, suppressing chronic inflammation, and attenuating cellular aging. These results suggest that Ninjin'yoeito has potential applications as a complementary therapy for age-related dry mouth.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"68 1","pages":"Article 100739"},"PeriodicalIF":2.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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