{"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<sup>high</sup> than in CD169<sup>low</sup> 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}
Xvni Tang, Liyan Ye, Ting Yan, Xiujuan Zheng, Lichao Yuan
{"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}
{"title":"Loss of miR-424 and miR-503 promotes decidualization of human endometrial stromal cells by increasing SCARA5 expression.","authors":"Tetsu Yamaguchi, Masashi Takamura, Hideno Tochigi, Yumi Mizuno, Yosuke Mizuno, Tomomi Sato, Shunsuke Tamaru, Kazuya Kusama, Kazuhiro Tamura, Yoshimasa Kamei, Takeshi Kajihara","doi":"10.1007/s00795-025-00431-5","DOIUrl":"https://doi.org/10.1007/s00795-025-00431-5","url":null,"abstract":"<p><p>This study aims to investigate the function of miR-424 and miR-503, identified as putative regulatory miRNAs of FOXO1, a key factor for decidualization. The expression of both miR-424 and miR-503 in human endometrial stromal cells (HESCs) were measured before and after decidualization. Then, HESCs were transfected with both miR-424 and miR-503 before decidualization. Quantitative reverse transcription PCR, actin staining analysis, migration assay, fluorescence immunostaining, and luciferase assay were performed. MiR-424 and miR-503 expression was decreased after decidualization. Overexpression of both miR-424 and miR-503 inhibited major decidual maker genes, including FOXO1, PRL, IGFBP1, WNT4, and SCARA5, and altered F-actin's subcellular distribution from the periphery to all over the cytoplasm, concomitantly increasing cell mobility. Moreover, immunohistochemical analysis revealed overexpression of both miRNAs resulted in FOXO1 protein accumulation in the cytoplasm. Knocking down FOXO1 decreased SCARA5 expression, revealing SCARA5 is a downstream target of FOXO1. In addition, a luciferase reporter assay confirmed that the 3'-untranslated region of FOXO1 mRNA is targeted by miR-424. These results suggest that both miRNAs may play an important role in endometrial decidualization by regulating transcriptional activity of FOXO1, which alters decidualization-related gene expression such as SCARA5.Abstract: Journal standard instruction requires an unstructured abstract; hence structured abstract changed to unstructured.Thank you for the correction. I approve this change.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630601","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":"Large number of CD68<sup>+</sup>/CD163<sup>+</sup> Hofbauer cells and characteristic vascular structural alterations in the placental villi of cases with placenta accreta spectrum.","authors":"Hazuki Kashiwagi, Kengo Shigehara, Terufumi Kubo, Yoshihiko Hirohashi, Tasuku Mariya, Kazuhiko Matsuo, Tomoyuki Minowa, Shin-Ichi Ishioka, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Toshihiko Torigoe","doi":"10.1007/s00795-025-00432-4","DOIUrl":"https://doi.org/10.1007/s00795-025-00432-4","url":null,"abstract":"<p><p>Placenta accreta spectrum (PAS) is a serious disease leading to complications and maternal death. The objective of the study was to characterize the placental villi and blood vessels of PAS villi histopathologically. We investigated 10 cases of PAS (five cases of placenta increta, two cases of placenta accreta, and three cases of placenta percreta) histologically. Immunohistochemical staining using anti-CD68 or anti-CD163 antibodies was performed to detect and count Hofbauer cells. Immunohistochemical staining with an anti-CD34 antibody was used to detect vascular endothelial cells, and the number and area of vessels were analyzed. The numbers of CD68-positive or CD163-positive Hofbauer cells were larger in PAS cases compared with control cases. The vascular area in villi was smaller in PAS cases compared with control cases. The number of blood vessels in villi was slightly higher in PAS cases than in control cases. The numbers of Hofbauer cells and vessels in villi were larger in PAS cases compared with control cases, whereas the area of vessels in villi was smaller in PAS cases compared with control cases. Although their biological meaning is elusive, these findings provide novel insights into the pathogenesis of PAS, particularly regarding the role of Hofbauer cells in immune-suppressive role and angiogenesis and the alterations in vascular structure and hemodynamics in the chorionic villi.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625313","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":"Mixed hepatocellular carcinoma and high-grade neuroendocrine neoplasm with ambiguous histopathological features: a case report.","authors":"Kentaro Tsuji, Makoto Abe, Saho Wakamatsu, Sayuri Hoshi, Nobuo Hoshi, Chisato Takagi, Noriyoshi Fukushima, Kaoru Hirabayashi","doi":"10.1007/s00795-024-00396-x","DOIUrl":"10.1007/s00795-024-00396-x","url":null,"abstract":"<p><p>Well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC) are distinct entities with different biological behavior. However, difficult cases showing equivocal morphology have been reported in some organs. Herein, we report a case of primary hepatic neuroendocrine neoplasm (NEN) with ambiguous histopathological features admixed with conventional hepatocellular carcinoma (HCC). A 70-year-old man with untreated chronic hepatitis B underwent left medial sectionectomy because of two incidental liver masses. On pathological examination, one of the resected tumors had intermingling NEN and HCC components. The NEN component consisted of relatively uniform tumor cells proliferating in trabecular, cord-like, or solid patterns with peripheral nuclear palisading. The tumor cells were immunopositive for synaptophysin, chromogranin A, cluster of differentiation 56 (CD56), and focally hepatocyte paraffin 1. p53 showed wild-type expression. The Ki-67 labeling index was 27% at the hot spot. Eleven months after the surgery, he died of a cerebral hemorrhage without evidence of recurrent liver cancer. The intermediate degree of differentiation and the modest proliferative activity can challenge the distinction between NEC and NET G3. While the coexisting HCC indicates NEC rather than NET in a pathogenetic viewpoint, such ambiguous tumor may not be as aggressive as typical NECs.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"62-68"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036288","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}
Solimar Ribeiro Carlete Filho, Luana Amorim Morais da Silva, Caio Rodrigues Maia, Paulo Roberto de Andrade Santos, Pollianna Muniz Alves, Pedro Paulo de Andrade Santos
{"title":"Oral pemphigus vulgaris diagnostic characteristics and treatment: a systematic review.","authors":"Solimar Ribeiro Carlete Filho, Luana Amorim Morais da Silva, Caio Rodrigues Maia, Paulo Roberto de Andrade Santos, Pollianna Muniz Alves, Pedro Paulo de Andrade Santos","doi":"10.1007/s00795-024-00414-y","DOIUrl":"10.1007/s00795-024-00414-y","url":null,"abstract":"<p><p>Pemphigus vulgaris (PV) is a rare, potentially fatal, immune-mediated chronic disease characterized by the presence of bullous intraepithelial lesions on mucous membranes and skin. This study aimed to perform a systematic literature review covering PV clinical and histopathological aspects and treatment. The literature searches were carried out in the Pubmed, Periódicos Capes, Scopus, Science Direct, Web of Science and Scielo databases. Articles in English or Spanish published from 2000 to 2022 comprising case reports, case series and literature reviews with case report were included. After the analyses, 21 articles were selected. PV generally presents in the third to sixth decades of life and exhibits no gender predilection. The disease manifests itself clinically through irregular and painful blisters that rupture, resulting in erosion and ulceration areas. Histopathologically, the presence of an intraepithelial cleft located above the basal layer and acantholysis are observed. Standard treatment encompasses systemic and topical corticosteroids, with prednisolone being widely employed. Management consists of a remission induction phase and a maintenance phase. An early and accurate diagnosis is paramount to quickly initiate treatment, resulting in more favorable prognoses, as the choice of treatment and responses depend on the severity of the disease. Registered at the International Prospective Register of Systematic Reviews (PROSPERO): Number CRD42024497313.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"1-22"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829248","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}
Yi Liu, XuanPeng Li, HaiWen Xu, Ke Sun, Hui Jun Gong, Cheng Luo
{"title":"Spinal cord stimulation induces Neurotrophin-3 to improve diabetic foot disease.","authors":"Yi Liu, XuanPeng Li, HaiWen Xu, Ke Sun, Hui Jun Gong, Cheng Luo","doi":"10.1007/s00795-024-00410-2","DOIUrl":"10.1007/s00795-024-00410-2","url":null,"abstract":"<p><p>Low-extremity ischemic disease is a common complication in diabetic patients, leading to reduced quality of life and potential amputation. This study investigated the therapeutic effect of spinal cord stimulation (SCS) on patients with diabetic foot disease and a rat model of diabetic foot injury. SCS was applied to patients with diabetic foot disease, with clinical assessments performed before and after therapy. Blood levels of NGF, BDNF, and NT-3 were determined by ELISA. A rat model of diabetic foot injury was established to validate NT-3's role in SCS therapy. SCS therapy improved the condition of patients with diabetic ischemic foot disease and promoted wound healing in the rat model. NT-3 levels significantly increased after SCS therapy in both patients and rats. Recombinant NT-3 administration improved wound healing and re-vascularization in the rat model, while NT-3 neutralization abrogated SCS's therapeutic effect. SCS improves the condition of patients with diabetic ischemic foot disease by inducing NT-3 production. Both SCS and NT-3 supplementation show therapeutic potential for ameliorating diabetic foot disease.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"43-52"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644472","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":"Morphological aberration of corneal nerves in hyposecretory dry eye guinea pigs.","authors":"Takeshi Kiyoi, Qiang He, Li Liu, Shijie Zheng, Hitomi Nakazawa, Junsuke Uwada, Takayoshi Masuoka","doi":"10.1007/s00795-024-00407-x","DOIUrl":"10.1007/s00795-024-00407-x","url":null,"abstract":"<p><p>Dry eye, a common ocular surface disease associated with tear film instability and corneal impairment, is frequently accompanied by ocular discomfort and pain. Recent research has shown that corneal nerve dysfunction may play a role in certain pathologies of dry eye; however, the details remain unclear. To clarify the aberration in corneal nerves underlying sensory abnormalities, in addition to corneal impairment in dry eye, we examined the morphological alterations of nerve fibers in the corneas excised from guinea pigs with dry eye, where the lacrimal glands were surgically excised. Guinea pigs with dry eye exhibited reduced tear volume, increased spontaneous blink frequency, and corneal epithelial damage. Simultaneously, the subbasal nerve plexus in the cornea visualized using an anti-tubulin βIII antibody partially outgrew and became convoluted. The morphology of peptidergic nerves containing calcitonin gene-related peptide, which may function as a polymodal nociceptor, was also altered. These results indicate that guinea pigs with excised lacrimal glands can serve as useful tools for investigating the neuronal mechanisms underlying corneal pathology in dry eyes. Additionally, chronic tear deficiency may considerably alter nerve structure, including peptidergic nerves in the cornea, accompanied by epithelial damage and increased blink frequency.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"34-42"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623548","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}