Medical Molecular Morphology最新文献

{"title":"HIFU induces reprogramming of the tumor immune microenvironment in a pancreatic cancer mouse model.","authors":"Toshihiro Yamaguchi, Shuji Kitahara, Aya Matsui, Jun Okamoto, Yoshihiro Muragaki, Ken Masamune","doi":"10.1007/s00795-025-00419-1","DOIUrl":"10.1007/s00795-025-00419-1","url":null,"abstract":"<p><p>This study evaluates the effects of different high-intensity focused ultrasound irradiation (HIFU) methods on local tumor suppression and systemic antitumor effects, including the abscopal effect, in a mouse model of pancreatic cancer. To ascertain the efficacy of the treatment, pancreatic cancer cells were injected into the thighs of mice and HIFU was applied on one side using continuous waves or trigger pulse waves. Then, tumor volume, tissue changes, and immune marker levels were analyzed. Both the irradiation methods suppressed tumor growth, with the trigger pulse wave showing stronger effects and the difference being significant. Tumor suppression was also observed on the non-irradiated side, suggesting an abscopal effect. These effects vary depending on the irradiation method used. We conclude that HIFU induces both local tumor suppression and a systemic immune response, suggesting its potential for combination with immunotherapy for the treatment of pancreatic cancer.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"137-148"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052984","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":"Investigation of the molecular mechanism of quercetin in inhibiting ankylosing spondylitis ossification via the bone morphogenetic protein/smad signaling pathway.","authors":"Zhenyu Li","doi":"10.1007/s00795-024-00417-9","DOIUrl":"10.1007/s00795-024-00417-9","url":null,"abstract":"<p><p>Ankylosing spondylitis (AS) is a chronic inflammatory disease involving the spine and bone joints, which is characterized by hyperosteogeny, ossification of ligaments, and ankylosis. Quercetin is a natural polyphenolic compound with various biological activities such as antioxidant, anti-inflammatory, and anti-tumor. It was to explore the effect of quercetin on AS ossification and its molecular mechanism. In vitro culture of AS mesenchymal stem cells was conducted. Cells were treated with 0, 10, 30, 60, and 80 μM quercetin, divided into control, 10 μM, 30 μM, 60 μM, and 80 μM groups. Alkaline phosphatase (ALP) staining, Alizarin Red staining, real-time quantitative polymerase chain reaction (qRT-PCR), and Western blot (WB) were employed to investigate the effect of quercetin on the expression of osteogenic-related genes and proteins. Additionally, bone morphogenetic protein (BMP) and Smad genes were knocked out to explore quercetin's regulation of BMP/Smad. In vivo experiments were conducted using 50 mice, including 10 in the normal group. An AS model was established in 36 mice, divided into negative control (n = 18, 0.9% saline) and quercetin groups (n = 18, quercetin). Safranin O-fast green (HE) staining and MicroCT scanning were performed before and 4 weeks after injection. In the 60 μM and 80 μM quercetin groups, ALP activity, Ca²⁺ deposition area, and relative protein/mRNA levels of BMP-1, BMP-2, Smad1, Smad4, and Smad5 in AS mesenchymal stem cells were significantly lower compared to the control, 10 μM, and 30 μM groups (P < 0.05). The 80 μM group exhibited lower levels than the 60 μM group (P < 0.05). In the siRNA + 80 μM group, the reduction in mRNA expression of BMP1, BMP2, Smad1, Smad4, and Smad5 was significantly greater compared to the siRNA group and the 80 μM group (P < 0.05). At 4 weeks post-injection, mice in the quercetin group showed significantly reduced severity of articular cartilage lesions, lymphocyte infiltration, and tissue edema, with no significant increase in sacroiliac joint fusion. Quercetin downregulates the expression of BMP and Smad-related proteins, inhibiting osteogenic differentiation of AS mesenchymal stem cells and effectively reducing ALP activity and Ca²⁺ deposition levels. These findings suggest that quercetin holds potential application value in the control and treatment of AS disease.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"114-125"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895381","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":"Ultrastructure of the small vessels in the myocardium in a patient with fatal systemic capillary leak syndrome.","authors":"Hiroaki Kawano, Koichi Kawamura, Koji Maemura, Shinji Okano","doi":"10.1007/s00795-025-00439-x","DOIUrl":"https://doi.org/10.1007/s00795-025-00439-x","url":null,"abstract":"<p><p>A 29-year-old Japanese woman was admitted to our hospital with fever, cardiogenic shock, and cardiac arrest and died 18 h after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019. Electron microscopy of the biopsied right-ventricular myocardium revealed extensive interstitial leakage of blood cells and plasma, damaged capillaries, and reticular vessel drainage into the Thebesian vein. These findings indicate that severe capillary leak and lumen occlusion due to damaged capillaries are the main features of systemic capillary leak syndrome.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989646","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":"Minichromosome maintenance 4 is associated with poor survival and stemness of patients with pancreatic cancer.","authors":"Yuto Fujiki, Akira Ishikawa, Narutaka Katsuya, Yuki Shiwa, Takafumi Fukui, Kazuya Kuraoka, Takeshi Sudo, Sho Tazuma, Yasutaka Ishii, Shiro Oka, Wataru Yasui, Shinji Mii","doi":"10.1007/s00795-025-00438-y","DOIUrl":"https://doi.org/10.1007/s00795-025-00438-y","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most well-known cancer types, with a persistently poor 5-year survival rate. We previously reported MCM4 as a molecule associated with cancer stem cells; however, its role in PDAC has not been reported. Therefore, in this study, we aimed to fill this gap in the literature. We analyzed MCM4 expression in 81 PDAC samples using immunohistochemistry (IHC). The functional role of MCM4 in PDAC was investigated using RNA interference in PDAC cell lines. Additionally, a single-cell analysis was conducted by downloading data from six PDAC cases. On IHC, high MCM4 expression was observed in 42 out of 81 (51.9%) PDAC cases. MCM4-positive PDAC was significantly associated with a higher pN grade. Furthermore, high MCM4 expression was linked to a significantly poorer prognosis and was identified as an independent prognostic factor in multivariate analysis. In PDAC cell lines, MCM4 knockdown impairs cell growth and spheroid formation. Single-cell analysis also revealed that MCM4-expressing cells were located upstream of the trajectory, with a cluster showing a correlation with KIFC1, which has been reported to be associated with cancer stemness. These results indicated the significance of MCM4 expression in PDAC and its association with cancer stemness.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022025","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":"Effects of platelet-rich plasma, platelet-rich fibrin and concentrated growth factor on flap survival: a study in a rat dorsal cross-region perforator flap model.","authors":"Peiwen Li, Ruiqi Jin","doi":"10.1007/s00795-025-00436-0","DOIUrl":"https://doi.org/10.1007/s00795-025-00436-0","url":null,"abstract":"<p><strong>Background: </strong>With the extensive application of flap surgery in clinical practice, it has been a matter of great concern to improve the survival rate of flap surgery for a long time. This study compared and explored the effect of the three generations of platelet concentrates (PCs), including platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF), on flap survival.</p><p><strong>Methods: </strong>After PRP, PRF, and CGF gels were observed by scanning electron microscope (SEM), their vascularizing effect were assessed by infrared thermal imager, flap survival experiment, arterial perfusion angiography, and immunohistochemical staining in a rat dorsal cross-region perforator flap model.</p><p><strong>Results: </strong>The fibrin of PRP gel showed irregular clumps and loose structure, while that of PRF and CGF gels formed 3D network structure with orderly arrangement and compact structure. In animal models, the use of all the three PCs can increase the number of vessels and the amount of blood perfusion in choke zones (all P < 0.05), thus improving the flap survival rate. Moreover, the effects of CGF and PRF were obviously better than those of PRP (all P < 0.05), but there was no significant difference between CGF and PRF (P > 0.05).</p><p><strong>Conclusions: </strong>PRP, PRF, and CGF all have a good effect on promoting vascularization, and can significantly improve the survival rate of dorsal cross-region perforator flap in rat model. Besides, PRF and CGF have greater potential in promoting vascularization than PRP.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009241","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":"Immunohistochemical investigation of the transcription factor PROX1 emphasizing on neuroendocrine neoplasms.","authors":"Kanata Kojima, Kouhei Sakurai, Tatsuya Ando, Yasuhiro Sakai, Mako Ochiai, Taku Kato, Hiroyasu Ito","doi":"10.1007/s00795-025-00437-z","DOIUrl":"https://doi.org/10.1007/s00795-025-00437-z","url":null,"abstract":"<p><p>Prospero homeobox protein 1 (PROX1) is aberrantly expressed in tumors, including neuroendocrine neoplasms (NENs); however, the detailed expression pattern remains elusive. This study aimed to immunohistochemically assess PROX1 expression. Immunohistochemistry (IHC) for PROX1 was performed on tissue microarrays of normal tissues (n = 107), NENs (n = 152) (small cell lung carcinoma [SCLC], lung carcinoid [LC], gastroenteropancreatic-NEN [GEP-NEN], esophageal neuroendocrine carcinoma [ENEC], medullary thyroid carcinoma [MTC], neuroblastoma [NB], and pheochromocytoma [PHEO]), and non-NENs (n = 469). In normal tissues, PROX1 was expressed in lymphatic endothelial cells and a subset of epithelial cells in the gastrointestinal tract and the distal convoluted tubules. In NENs, the positive expression was observed in the nucleus of tumor cells in 19/26 SCLC (73.1%), 13/16 LC (81.3%), 10/15 GEP-NEN (66.7%), 2/2 ENEC (100%), 17/43 MTC (39.5%), 1/25 NB (4.0%), and 0/25 PHEO (0%). Although PROX1 was negative in many non-NENs, our analysis revealed high expression in certain cases with medulloblastoma and one case with juvenile granulosa cell tumor. PROX1 was expressed in specific cases with epithelial NENs and some cases with non-NENs. Analysis of PROX1 should provide insights into the molecular characteristics of distinct tumors.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034515","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":"Transmission electron microscopic analysis of pancreatic ductal adenocarcinoma cell spheres formed in 3D cultures.","authors":"Yuuki Shichi, Masakazu Fujiwara, Fujiya Gomi, Keisuke Nonaka, Fumio Hasegawa, Seiichi Shinji, Hirofumi Rokutan, Tomio Arai, Kimimasa Takahashi, Toshiyuki Ishiwata","doi":"10.1007/s00795-025-00435-1","DOIUrl":"https://doi.org/10.1007/s00795-025-00435-1","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) cell lines are classified into two types: epithelial and mesenchymal protein-expressing. Using scanning electron microscopy, we reported that these two groups differ in terms of morphology when they formed tumor spheres under three-dimensional (3D) culturing. In this study, we used transmission electron microscopy (TEM) to examine the intracellular microstructures of five epithelial and three mesenchymal PDAC cell lines in 3D culture, and compared them to the morphologies of the same cell types in two-dimensional (2D) cultures. Microvilli were present in all PDAC cells cultured in 2D and 3D, and were well developed in epithelial PDAC cells. Desmosome-like structures were only observed in epithelial PDAC cells, and were more common in 3D cultures. Secretory granules were observed in epithelial PDAC and mesenchymal PANC-1 cells, and were more common in 3D cultures. Intracytoplasmic lumina were only observed in epithelial PK-59 and T3M-4 cells cultured in 3D. Abundant filamentous aggregates were observed in 2D-cultured T3M-4 and MIA PaCa-2 cells. By contrast, entosis was observed in 3D-cultured PK-59, PK-1, and KP4 cells. Microstructural differences enhanced by 3D culturing revealed significant phenotypic diversity among PDAC cells, and may provide key insights into curing intractable pancreatic cancer.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780173","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":"Aging potentially reduces CD169 expression in sinus macrophages of pelvic lymph nodes.","authors":"Yuki Ibe, Yojiro Ozaki, Toshiki Anami, Hiromu Yano, Yukio Fujiwara, Hidekazu Nishizawa, Ryoma Kurahashi, Takanobu Motoshima, Yoji Murakami, Junji Yatsuda, Yoshihiro Komohara, Tomomi Kamba","doi":"10.1007/s00795-025-00433-3","DOIUrl":"https://doi.org/10.1007/s00795-025-00433-3","url":null,"abstract":"<p><p>The number of patients with prostate cancer has been increasing around the world. Although anticancer immunotherapy targeting the immune checkpoint molecules has been approved for many types of cancer, no significant anti-cancer effects have been observed in patients with prostate cancer. Lymph node sinus macrophages (LSMs) are known to work as antigen-presenting cells, which are critical for anticancer immune responses. Previous studies have suggested that CD169 expression in LSMs affects anticancer immune responses in several cancers, including prostate cancer. In the present study, we aimed to examine the correlation between the tumor immune microenvironment and activation status of LSMs in patients with prostate cancer. Forty-two cases of high-risk localized prostate cancer treated using robot-assisted laparoscopic radical prostatectomy and lymph node dissection between 2017 and 2021 were enrolled. CD169 expression in LSMs was examined by immunohistochemistry. The results indicated that CD169 expression in LSMs was significantly decreased in older (≥ 75 years) compared with younger patients. However, no significant correlation was found between CD169 expression and any other clinicopathological factors. In addition, CD3- and CD8-postitive lymphocytes in primary cancer tissues were evaluated in the same cases, and their correlations with CD169 expression in LSMs were tested. Although these lymphocytes tended to be higher in CD169^high than in CD169^low cases, the difference was not statistically significant. In conclusion, we found that CD169 expression was upregulated in older patients and tended to be related to T cell infiltration in cancer tissues. Therefore, the downregulation of CD169 in LSMs might be involved in the reduced anticancer immune response in prostate cancer.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700596","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":"The cross-talk between NRF2 and apoptosis in cancer.","authors":"Elmira Aboutalebi Vand Beilankouhi, Bahareh Yousefi, Niloofar Sadat Hadian, Reza Safaralizadeh, Mohammad Valilo","doi":"10.1007/s00795-025-00434-2","DOIUrl":"https://doi.org/10.1007/s00795-025-00434-2","url":null,"abstract":"<p><p>Cancer is one of the common diseases that affects people in the society, the prevalence of which has decreased somewhat in recent years. Various genetic and environmental factors play a role in the development and progression of cancer. NRF2 is a transcriptional regulator that controls the expression of antioxidant response element-related genes. It plays an important role in regulating the physiological and pathophysiological consequences of oxidant exposure. NRF2 is also responsible for regulating the expression of various cellular protective genes. NRF2 activity is regulated at multiple levels including protein stability, transcription, and post-transcription. The Keap1-Cul3-Rbx1 axis is the most prominent regulator of NRF2 activity. Apoptosis is a type of programmed cell death that is initiated by two intrinsic and extrinsic pathways. Caspases play a major role in this cell death pathway. Apoptosis pathway is related to many cells signaling pathways that are interconnected. Disruption in one pathway affects the other pathway. One of these signaling pathways is the NRF2 pathway, which is associated with apoptosis, which are interconnected and play an important role in disease prevention or progression. Therefore, in this study, we decided to investigate the relationship between NRF2 and apoptosis in cancer.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700600","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":"Expression of Bax and Bcl-2 in the placenta from pre-term, term, and post-term deliveries: immunohistochemical analysis.","authors":"Xvni Tang, Liyan Ye, Ting Yan, Xiujuan Zheng, Lichao Yuan","doi":"10.1007/s00795-025-00429-z","DOIUrl":"https://doi.org/10.1007/s00795-025-00429-z","url":null,"abstract":"<p><p>The placenta is the most critical organ during pregnancy and its developmental status directly impacts fetal health. Placental dysfunction is associated with various pregnancy complications, including preterm birth, fetal growth restriction, and premature rupture of membranes (PROM). This study aimed to elucidate the expression changes of Bax and Bcl-2 and their association with pregnancy-related complications, providing new insights into placental dysfunction during pregnancy and offering a theoretical foundation for clinical diagnosis and prevention. The placental samples from 118 late pregnant women were retrospectively analyzed. They were assigned into pre-term, term, post-term, PROM, and non-PROM groups based on gestational age and the occurrence of PROM. Immunohistochemistry (IHC) staining was performed to gauge the Bax and Bcl-2 expressions in placenta. Receiver operating characteristic (ROC) curve was subsequently conducted to assess their associated with efficacy for PROM. The weight and volume of placentas in the pre-term group were sharply smaller to those in the term and post-term groups, with no apparent fibrosis or calcification observed. The term and post-term groups exhibited marked elevated Bax expression in the parturient group in contrast to the non-parturient group (P < 0.05), while there existed no substantial significance in Bcl-2 expression. The area under the curve (AUC) for Bax and Bcl-2 was 0.975 and 0.596, respectively, with a combined associated with value of 0.978, higher to single predictions. Bax and Bcl-2 expressions in late pregnancy placentas were associated with the onset of parturient status and PROM and their combined prediction exhibited accurate PROM predicted. These findings offered a new perspective for understanding the physiological and pathological changes of the placenta during pregnancy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657627","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}