{"title":"Effect of combination of osteoblasts and octacalcium phosphate collagen composite on bone regeneration in rat calvarial bone defect.","authors":"Hiroshi Kato, Satoki Nishimura, Shoko Onodera, Akira Watanabe","doi":"10.1007/s00795-026-00465-3","DOIUrl":"10.1007/s00795-026-00465-3","url":null,"abstract":"<p><p>This study aimed to assess the effect of a combination of osteoblasts and octacalcium phosphate collagen composite (OCP/Col) on bone regeneration. In oral and maxillofacial surgery, OCP/Col has been clinically used as artificial bone. Although OCP/Col was reported to promote osteoblast differentiation, few studies have reported on its use in combination with cell transplantation. Moreover, its effects are not fully clarified. Therefore, we evaluated the osteogenic properties of a combination of OCP/Col and osteoblasts. We found that osteoblasts cultured in OCP/Col differentiated toward osteolineage, expressing several osteoblast markers. In animal experiments, the cell transplantation group showed promotion of osteoblast differentiation and stromal formation in the tissues compared with the OCP/Col group. These findings indicate that combining osteoblasts and OCP/Col would be beneficial for bone regeneration therapy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"180-188"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Significance of p53-binding protein 1 as an in situ DNA damage marker for ulcerative colitis.","authors":"Nazigul Zhumagazhiyeva, Miho Doo, Yerkezhan Sailaubekova, Yoshiyuki Matsumoto, Iori Fujisawa, Eri Yoshioka, Masanobu Ikeda, Keiichi Hasiguchi, Maiko Tabuchi, Yasuaki Shibata, Takahiro Motoyama, Yuki Matsuoka, Katsuya Matsuda, Hisamitsu Miyaaki, Yuko Akazawa","doi":"10.1007/s00795-026-00462-6","DOIUrl":"10.1007/s00795-026-00462-6","url":null,"abstract":"<p><p>Ulcerative colitis is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. The extensive and persistent mucosal damage associated with ulcerative colitis (UC) can contribute to carcinogenesis, thereby underscoring the significant clinical interest in identifying an in situ marker. p53-binding protein (53BP1) is a DNA damage response (DDR) molecule that localizes at sites of double-strand breaks. Herein, we investigated the in situ DDR in UC by evaluating 53BP1 immunofluorescence. Our study revealed a significant increase in abnormal 53BP1 foci, defined as three or more foci and/or foci larger than 1 µm within the nucleus, in patients with UC compared to controls. Furthermore, the presence of abnormal 53BP1 foci in UC correlated with the severity of symptoms, endoscopic gradings, serological and histopathological inflammation. Of note, 53BP1 foci were observed in the colon mucosa of patients in remission, indicating that 53BP1 is a sensitive DDR marker. In addition, large 53BP1 foci, indicative of a severe DDR, were more prevalent in patients with colitic cancer than in controls. In conclusion, our findings suggest that 53BP1 may serve as a in situ marker reflecting the extent of the DDR in UC.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"200-208"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aggressive multiple myeloma with lymph node involvement, loss of CD138, and adipophilin-positive cytoplasmic vacuolization: a case report.","authors":"Yoshihiko Kondo, Seiichiro Nakabeppu, Hiromu Yano, Kenji Ishitsuka, Tadahito Urakado, Yukio Fujiwara, Masahiro Yamamoto, Kennosuke Karube, Yoshihiro Komohara","doi":"10.1007/s00795-026-00460-8","DOIUrl":"10.1007/s00795-026-00460-8","url":null,"abstract":"<p><p>We describe a rare and aggressive case of multiple myeloma (MM) characterized by extensive lymph node involvement, loss of CD138 expression, and adipophilin (ADP)-positive cytoplasmic vacuolization, highlighting the role of lipid metabolism in disease aggressiveness. An 83-year-old woman presented with painless cervical lymphadenopathy and widespread osteolytic lesions. Bone marrow examination confirmed MM, while lymph node biopsy showed diffuse infiltration of atypical lymphoid cells with numerous tingible body macrophages, initially mimicking a high-grade lymphoma. Immunophenotyping showed CD3/CD5/CD20/CD23 negativity, focal CD138/CD79a positivity, diffuse MUM1 and κ-light chain positivity, and a high Ki-67 index. Compared with bone marrow plasma cells, lymph node MM cells exhibited prominent cytoplasmic vacuoles and nuclear enlargement. Immunohistochemistry demonstrated ADP positivity in lymph node lesions but not in bone marrow MM cells, suggesting metabolic reprogramming toward lipid utilization. Despite anti-myeloma therapy, the disease rapidly progressed, and the patient died within two months. This case underscores the clinical significance of CD138 down-regulation as a marker of dedifferentiation and poor prognosis, and suggests that altered lipid metabolism may contribute to the aggressiveness of metastatic MM. To the best of our knowledge, this is the first MM case with lymph node involvement showing CD138 down-regulation and ADP positivity.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"235-240"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Eldegwi, Basma Gadelhak, Nadia Bassiouny, Mohamed Fawzy, Khadiga M Ali
{"title":"Integration of L1CAM and β-catenin immunohistochemistry for prognostic risk stratification of endometrial carcinoma: a practical approach for resource-limited settings.","authors":"Sara Eldegwi, Basma Gadelhak, Nadia Bassiouny, Mohamed Fawzy, Khadiga M Ali","doi":"10.1007/s00795-026-00464-4","DOIUrl":"10.1007/s00795-026-00464-4","url":null,"abstract":"<p><p>Accurate prognostic stratification of endometrial carcinoma (EC) remains challenging in resource-limited settings lacking molecular sequencing. We investigated whether immunohistochemical (IHC) assessment of combined L1CAM/β-catenin expression, integrated with mismatch repair (MMR) status and p53 expression, could refine prognostic risk stratification in EC in absence of POLE sequencing. A retrospective cohort study evaluated 140 surgically staged EC cases for L1CAM, β-catenin MMR, and p53 IHC expression with clinicopathological correlation. Survival analysis was performed on 111 cases (median follow up:38 months). L1CAM and β-catenin demonstrated mutually exclusive expression patterns (27.1% and 6.4% respectively; 66.5% double negative). L1CAM + tumors demonstrated significantly worse disease specific survival (DSS) (HR:4, 95%CI: 1.6-9.9) and disease-free survival (DFS) (HR:4.9, 95%CI: 2.2-11.4), compared to double-negative (64.5% vs 90.3% DSS, 41.9% vs 12.5% relapse rate). β-catenin alone didn't predict outcome but contributed to prognostic refinement when combined with L1CAM status. This prognostic gradient persisted in the pMMR/p53wt subgroup (L1CAM + mean DFS: 21.7 months vs double-negative: 69.6 months; p ≤ 0.001). The combined L1CAM/β-catenin IHC profile categorized patients into prognostically distinct categories and offers pragmatic prognostic refinement, particularly for pMMR/p53wt tumors in centers lacking POLE sequencing. This approach doesn't replace comprehensive molecular testing and requires prospective validation before clinical implementation.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"209-225"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of S1P/S1PR on bone metabolism in bisphosphonate-related osteonecrosis of the jaws.","authors":"Ting Guo, Yuhao Wang, Dianri Wang, Wenbin Yang, Xiye Sun, Jiyuan Liu, Jian Pan","doi":"10.1007/s00795-026-00461-7","DOIUrl":"10.1007/s00795-026-00461-7","url":null,"abstract":"<p><p>Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a major adverse effect of bisphosphonates, yet its underlying pathogenesis remains poorly understood. Bone metabolism and remodeling relies on the interaction between osteoblasts (OBs) and osteoclasts (OCs). Sphingosine 1-phosphate (S1P), a bioactive sphingolipid metabolite, is an important mediator of OC-OB communication. In this study, we aimed to investigate the role of the S1P/S1P receptor (S1PR) axis in the development of BRONJ. A co-culture system was used to examine the interaction between OCs and OBs. Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of related proteins and messenger ribonucleic acids (mRNAs). Finally, an in vivo BRONJ mouse model was used to validate the role of S1P/S1PR axis in disease progression. In our study, we showed that zoledronate (ZOL) promoted S1P secretion from OCs and enhanced the migration of osteoclast precursor cells (OCPs) through S1PR signaling. In addition, OCs promoted the excessive osteogenic differentiation and migration of OBs via S1P/S1PR axis. Importantly, pharmacological inhibition of S1PR facilitated the recovery of BRONJ-like lesions in vivo. In conclusion, these findings indicate that the S1P/S1PR axis plays an important role in the pathogenesis of BRONJ and may represent a potential therapeutic target for its treatment.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"189-199"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acute liver failure as the first symptom of childhood systemic lupus erythematosus: a case report and review of the literature.","authors":"Yutong Song, Jing Hao","doi":"10.1007/s00795-025-00452-0","DOIUrl":"10.1007/s00795-025-00452-0","url":null,"abstract":"<p><p>Although systemic lupus erythematosus (SLE) can affect multiple organ systems, manifestations within the digestive tract are not typically conspicuous during the early phase of the disease. The liver damage caused by SLE is mild and insidious. Patients with SLE presenting with acute liver failure as the primary manifestation are significantly rarer in clinical diagnosis. The absence of diagnostic criteria for digestive system manifestation in SLE complicates the diagnosis of lupus as the underlying cause, particularly during the initial presentation. Timely recognition of the disease and commencement of immunosuppressive treatment are crucial for enhancing clinical outcomes. This article reports a rare case of SLE in a 9-year-old Chinese girl presenting with acute liver failure as the initial symptom. The child lacked typical lupus features such as skin and joint manifestations, making the initial diagnosis extremely challenging. The diagnosis relied on key liver pathological examinations and positive serological lupus-specific antibodies, and gene sequencing identified the c.740C > T (p.A247V) mutation of the TREX1 gene. After treatment, her condition improved. This case highlights the importance of early immunological and genetic screening in pediatric patients with unexplained acute liver failure to identify potential SLE. This case represents the first reported instance of pediatric SLE presenting with acute liver failure as the initial manifestation, associated with the c.740C > T (p.A247V) mutation. These findings highlight the critical importance of a multi-modal diagnostic approach-encompassing immunological, pathological (biopsy), and genetic assessments-for the evaluation of children with such atypical presentations.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"226-234"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"APC in the nervous system.","authors":"Takao Senda, Nami O Yamada, Takanori Onouchi","doi":"10.1007/s00795-026-00463-5","DOIUrl":"10.1007/s00795-026-00463-5","url":null,"abstract":"<p><p>The APC (adenomatous polyposis coli) gene, which was first discovered as a colorectal cancer suppressor gene, is highly expressed in the nervous system. The Apc gene/Apc protein is deeply involved in brain development and morphogenesis. In the postnatal brain, Apc/Apc is involved in synaptic transmission, axon growth, and intracellular transport. Apc/Apc expressed in glial cells is involved in glial cell differentiation and neural circuit formation through glial cell functions. Reports from disease model animals and familial adenomatous polyposis (FAP) patients suggest that APC may be involved in the onset of autism, cognitive impairment, and schizophrenia.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"161-168"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased density of CD103-positive tissue-resident memory T cells predicts favorable response to immunotherapy in oral cancers.","authors":"Mayuko Yamashita, Hiromu Yano, Yoshihiro Komohara, Rin Yamada, Daiki Yoshii, Yukio Fujiwara, Yuki Seki, Masatoshi Hirayama, Kenta Kawahara, Akiyuki Hirosue, Ryoji Yoshida, Hideki Nakayama","doi":"10.1007/s00795-026-00473-3","DOIUrl":"https://doi.org/10.1007/s00795-026-00473-3","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have become an important therapeutic option for oral cancers; however, reliable biomarkers predicting treatment efficacy remain limited. In this study, we investigated the association between intratumoral immune cell subsets, regional lymph node (RLN) immune status, and clinical responses to ICIs in patients with recurrent oral cancer. Pretreatment tumor tissues and RLNs were analyzed by immunohistochemistry to evaluate tumor-infiltrating lymphocytes, including CD8<sup>+</sup>, CD103<sup>+</sup>, CD3<sup>+</sup>, ICOS<sup>+</sup>, and CD163<sup>+</sup> cells, as well as programmed death-ligand 1 (PD-L1) expression and CD169<sup>+</sup> sinus macrophages. Treatment responses were assessed according to RECIST version 1.1. Responders to ICIs exhibited higher densities of CD8<sup>+</sup> and CD103<sup>+</sup> T cells compared with non-responders, whereas no significant associations were observed for CD3<sup>+</sup>, ICOS<sup>+</sup>, CD163<sup>+</sup> cells, or PD-L1 expression. Elevated pretreatment serum C-reactive protein (CRP) levels were associated with poorer responses. CD169<sup>+</sup> sinus macrophages in RLNs did not correlate significantly with treatment efficacy or T-cell infiltration. These findings suggest that intratumoral effector and tissue-resident memory-like T-cell infiltration, together with systemic inflammatory status, may influence ICI efficacy in recurrent oral cancer, and could improve patient stratification for immunotherapy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lipid metabolic reprogramming in ovarian cancer: molecular mechanisms and therapeutic implications.","authors":"Naomi Nakayama, Daisaku Asai, Tomoka Ishibashi, Tsubasa Maejima, Kentaro Nakayama","doi":"10.1007/s00795-026-00469-z","DOIUrl":"https://doi.org/10.1007/s00795-026-00469-z","url":null,"abstract":"<p><p>Lipids play diverse roles in cellular homeostasis, and dysregulation of lipid metabolism is implicated in a wide spectrum of diseases, including cancer. Ovarian cancer cells exhibit profound metabolic alterations that support autonomous proliferation under conditions of hypoxia and nutrient limitation. Although tumor angiogenesis occurs, insufficient and fragile neovasculature often limits nutrient supply, necessitating metabolic adaptation. Among these adaptations, lipid metabolic reprogramming has emerged as a critical feature that supports tumor growth, survival, invasion, and therapeutic resistance. Alterations in fatty acid synthesis, β-oxidation, lipid uptake, and inflammatory lipid metabolism collectively contribute to the malignant phenotype. This review summarizes current knowledge of lipid metabolic regulation in ovarian cancer, with particular emphasis on key enzymes and their regulatory mechanism and discusses potential implications for therapeutic targeting from a molecular and morphological perspective.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}