Histology and histopathology最新文献

{"title":"Hsa_circ_0088036 promotes tumorigenesis and chemotherapy resistance in hepatocellular carcinoma via the miR-140-3p/KIF2A axis.","authors":"Zhong Wang, Lei Wang, Guoqing Yin, Heng Li, Rong Zhang, Yuan Feng, Wen Chang","doi":"10.14670/HH-18-849","DOIUrl":"10.14670/HH-18-849","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. There are limited treatment options, particularly for chemotherapy-resistant HCC patients. Circular RNA hsa_circ_0088036 was associated with the development of bladder cancer and non-small cell lung cancer. However, whether it might be a potential therapeutic target for HCC remains elusive.</p><p><strong>Methods: </strong>Hsa_circ_0088036 expression was detected in HCC tumor tissues and cell lines using real-time PCR. The influences of hsa_circ_0088036 on proliferation and invasion as well as chemotherapy sensitivity in HCC cells were investigated by gain- and loss-of-function analyses. Associations among hsa_circ_0088036, miR-140-3p, and KIF2A were validated by real-time PCR, miRNA pull-down assay, dual-luciferase reporter assay, and western blot. Furthermore, a rescue experiment using KIF2A overexpression was performed to evaluate the regulatory mechanism of hsa_circ_0088036 in HCC cells. Additionally, the effect and mechanism of hsa_circ_0088036 were confirmed in a xenograft mouse model.</p><p><strong>Results: </strong>Hsa_circ_0088036 was highly expressed in HCC tissues and cells, with even higher expression in oxaliplatin-resistant cells. This expression was positively correlated with tumor size and TNM stage of the patients. Overexpression of hsa_circ_0088036 promoted the proliferation and invasion of HCC cells, while silencing mediated the opposite effects. Meanwhile, knockdown of hsa_circ_0088036 enhanced chemotherapy sensitivity, including oxaliplatin, doxorubicin, and sorafenib, in HCC cells. Furthermore, hsa_circ_0088036 silencing inhibited tumor growth and increased oxaliplatin sensitivity <i>in vivo</i>. Mechanically, hsa_circ_0088036 functioned via the miR-140-3p/KIF2A axis with the activation of PI3K/Akt and Notch signaling pathways.</p><p><strong>Conclusions: </strong>Hsa_circ_0088036 promoted HCC tumorigenesis and chemotherapy resistance by activating the PI3K/Akt and Notch pathways through regulating miR-140-3p/KIF2A signaling. Thus, hsa_circ_0088036 may be a potential therapeutic target in chemotherapy-resistant HCC.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1239-1251"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM22 mechanism promoting KAT2A ubiquitination degradation to regulate ferroptosis in hepatocellular carcinoma cell invasion and metastasis.","authors":"Wei Wang, Xiaoshan Chen, Wei Wei","doi":"10.14670/HH-18-856","DOIUrl":"10.14670/HH-18-856","url":null,"abstract":"<p><strong>Objective: </strong>Hepatocellular carcinoma (HCC) is a highly fatal cancer. This study aims to investigate the underlying mechanism of tripartite motif-containing 22 (TRIM22) in HCC cell invasion and metastasis through the K (lysine) acetyltransferase 2A (KAT2A)/glutathione peroxidase 4 (GPX4) axis.</p><p><strong>Methods: </strong>Human HCC cells BEL7405 were cultured <i>in vitro</i> and treated with MG-132, Ferrostain-1, pcDNA3.1-TRIM22, pcDNA3.1-KAT2A, or pcDNA3.1-NC. TRIM22-KAT2A interaction and KAT2A ubiquitination level, cell proliferation, invasion, migration, and histone H3 lysine 9 acetylation (H3K9ac) enrichment level on the GPX4 promoter were assessed by Co-IP, CCK-8, Transwell, and ChIP-qPCR assays. Mice were injected subcutaneously with Lv-oe-NC or Lv-oe-TRIM22 BEL7405 cells via the tail vein. Tumor proliferation and levels of TRIM22, KAT2A, GPX4, Fe²⁺, malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) in tissues and cells were evaluated by immunohistochemistry, RT-qPCR, western blot, and kits.</p><p><strong>Results: </strong>oe-TRIM22-treated BEL7405 cells exhibited increased TRIM22 expression, and abated KAT2A protein expression and malignant cell biological behaviors, which were partially reversed by upregulating KAT2A or suppressing ferroptosis. TRIM22 interacted with KAT2A, which was ubiquitinated to regulate GPX4 histone acetylation. TRIM22 overexpression elevated Fe²⁺, MDA, and ROS levels and cell death, and diminished GSH, GPX4, and H3K9ac enrichment levels, whereas further overexpression of KAT2A brought about opposite trends. TRIM22 suppressed HCC growth and metastasis by mediating ferroptosis through the KAT2A/GPX4 axis.</p><p><strong>Conclusions: </strong>TRIM22 promoted KAT2A ubiquitination degradation to reduce H3K9ac enrichment levels in the GPX4 promoter region, and facilitated ferroptosis, thereby inhibiting HCC cell invasion and metastasis and <i>in vivo</i> growth and metastasis.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1295-1307"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of the dopaminergic system in toxoplasmic encephalitis neuroimmunopathogenesis.","authors":"Tuğçe Anteplıoğlu, Gungor Cagdas Dincel, Mehmet Eray Alçiğir, Merve Bışkın Türkmen, Tilbe Su Yapici, Oğuz Kul, Ebtsam Al-Olayan, Mohammad Y Alshahrani, Saeed El-Ashram","doi":"10.14670/HH-18-877","DOIUrl":"10.14670/HH-18-877","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i> (<i>T. gondii</i>), a parasitic intracellular protozoan, can establish a chronic infection in the host brain and cause significant neuropathology. The current study aimed to determine the role of Tyrosine Hydroxylase (TH), Dopamine Receptor D1 (D1R), Nuclear Receptor Related-1 (Nurr1), and Dopamine Transporter (DAT) expression in the neuroimmunopathogenesis of toxoplasmic encephalitis (TE) at 15, 30, 45, and 60 days after infection with <i>T. gondii</i>. Additionally, the study investigated whether there was a correlation between the markers on these critical days, which had yet to be explored. The results showed that TH expression in brain tissue of BALB/c mice was significantly increased in all infected groups compared with healthy controls (<i>p</i><0.05). However, other striking findings of the study were that D1R, DAT, and Nurr1 expression were significantly decreased in all infected groups compared with healthy controls, in contrast to TH expression (<i>p</i><0.05). Study findings regarding behavioral changes in chronic <i>T. gondii</i>-infected laboratory animals and humans with TE provide important evidence of the relationship between neuropsychiatric diseases and <i>T. gondii</i> infection. By elucidating the pathogenesis of the disease in detail, treatment protocols that consider these coordinated changes in expression that vary from day to day can be developed.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1227-1237"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of TBRG4 suppresses the migration, invasion, and epithelial-to-mesenchymal transition of pancreatic cancer cells via TGF-β/smad3 signaling.","authors":"Xiao Ye, Xiaolin Zheng, Ling Zhu","doi":"10.14670/HH-18-871","DOIUrl":"10.14670/HH-18-871","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, with a low five-year survival rate of less than 10%. Transforming growth factor β regulator 4 (TBRG4) is differentially expressed in PC tissues, but its specific functions and regulatory role in PC have not been clarified.</p><p><strong>Methods: </strong>TBRG4 mRNA expression in PC cells was measured by qRT-PCR. Protein levels of TBRG4, key markers related to the epithelial-mesenchymal transition (EMT) process, and factors related to the TGF-β/smad3 pathway were quantified by western blot. The migratory and invasive abilities of PC cells were evaluated by wound healing and Transwell assays, respectively. Spearman's correlation analysis was performed to analyze the expression correlation between TBRG4 and TGF-β1 (or SMAD3). Xenograft mouse models were established to explore the <i>in vivo</i> role of TBRG4.</p><p><strong>Results: </strong>The mRNA and protein expression of TBRG4 were elevated in PC cells. TBRG4 knockdown repressed PC cell migration, invasion, and the EMT process. Moreover, TBRG4 activated TGF-β/smad3 signaling in PC cells and positively correlated with TGF-β1 (or SMAD3) expression in PC tissues based on bioinformatics analysis. Furthermore, SRI-011381 (an agonist of TGF-β1) counteracted the inhibitory influence of TBRG4 knockdown on PC cellular behaviors, and SB431542 (an inhibitor of the TGF-β type I receptor) treatment countervailed the promoting influence of TBRG4 overexpression on PC cell invasion, migration, and EMT. Results of <i>in vivo</i> assays verified that TBRG4 silencing inhibited tumorigenesis and TGF-β/smad3 signaling.</p><p><strong>Conclusion: </strong>The silencing of TBRG4 inhibits PC cell invasion, migration, EMT, and tumorigenesis by inactivating TGF-β/smad3 signaling.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1309-1319"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin inhibits the activation of microglia and cough sensitivity of guinea pigs exposed to PM2.5.","authors":"Shu Zhang, Li Long, Senlin Chai, Mingtong Lin, Hankun Lu, Xuemei Liu, Yaowei He, Rong Dong, Zhe Chen","doi":"10.14670/HH-18-850","DOIUrl":"10.14670/HH-18-850","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed to examine the impact of melatonin on mitigating brain inflammation and cough sensitivity resulting from exposure to particulate matter 2.5 (PM2.5).</p><p><strong>Methods: </strong>Guinea pigs were randomly assigned to the blank control group, normal saline group, PM2.5 exposure group, and PM2.5 exposure + melatonin group. The PM2.5 exposure and PM2.5 exposure + melatonin groups were given intranasal instillations of PM2.5 suspension twice daily for 28 consecutive days. Starting on day 21, the PM2.5 exposure + melatonin group was treated with an intraperitoneal injection of melatonin at 10 pm. Cough sensitivity to citric acid, microglia activation, IL-1β and TNF-α levels in the airway and dorsal vagal complex (DVC), and ultrastructural changes in neurons within the DVC were assessed.</p><p><strong>Results: </strong>The PM2.5 exposure group exhibited a significantly higher cough count to citric acid challenge (29.1±5.7 coughs) compared with the PM2.5 exposure + melatonin group (18.8±4.1 coughs), normal saline group (8.4±2.1 coughs), and blank control group (7.7±1.8 coughs). In addition, cough latency was shorter in the PM2.5 exposure group (26.9±6.5 seconds) than in the PM2.5 exposure + melatonin group (36.6±12.4 seconds), normal saline group (43.4±14.7 seconds), and blank control group (47.0±13.0 seconds). The PM2.5 exposure + melatonin group showed significantly reduced IL-1β (105.3±14.3 pg/ml) and TNF-α levels (113.0±23.5 pg/ml) in the DVC, as well as in the bronchoalveolar lavage fluid (IL-1β: 24.92±5.14 pg/ml, TNF-α: 12.72±3.99 pg/ml) compared with the PM2.5 exposure group (in the DVC: IL-1β: 132.7±17.6 pg/ml, TNF-α: 143.8±30.4 pg/ml; in the bronchoalveolar lavage fluid: IL-1β: 34.0±5.3 pg/ml; TNF-α: 15.8±0.8 pg/ml). Microglia in the DVC were less activated in the PM2.5 exposure + melatonin group (25.1±5.4) than in the PM2.5 exposure group (54.6±9.9). Furthermore, the PM2.5 exposure group exhibited an impaired blood-brain barrier in the DVC, which tended to alleviate the PM2.5 exposure + melatonin group.</p><p><strong>Conclusions: </strong>Exposure to PM2.5 induces airway inflammation, central facilitation, and heightened cough sensitivity in guinea pigs. Melatonin significantly inhibits microglia activation and reduces airway and DVC inflammation, which might contribute to attenuated cough hypersensitivity.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1253-1260"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental regulation of GABA_B receptors and downstream molecules in the mouse brain.","authors":"Carolina Aguado, Ana Fajardo-Serrano, Rocío Alfaro-Ruiz, María Llanos Martínez-Poyato, Ana Esther Moreno-Martínez, Sebastián García-Madrona, Alberto Roldán-Sastre, Pablo Alonso-Gómez, Miriam Fernández, Ricardo Puertas-Avendaño, Ryuichi Shigemoto, Kirill A Martemyanov, Rafael Luján","doi":"10.14670/HH-18-970","DOIUrl":"https://doi.org/10.14670/HH-18-970","url":null,"abstract":"<p><p>Metabotropic GABA (GABA_B) receptors have modulatory functions on neuronal excitability and neurotransmitter release. To fulfil these functions, GABA_B receptors form macromolecular signaling complexes with G proteins, effectors, and other associated proteins. Here we investigated the postnatal development of GABA_B receptors (GABA_B1 and GABA_B2 subunits) in mouse brain, focusing on potential similarities in the spatial and temporal expression pattern of their associated proteins Ca_V2.1, Gα_o, Gβ5, and RGS7, using histoblots, immunofluorescence, and immunoelectron microscopic techniques. At all ages analyzed, histoblot showed that the six proteins were widely expressed in the brain, with mostly an overlapping pattern throughout postnatal development. In the hippocampus, immunoelectron microscopy and quantitative analysis of immunoparticles for GABA_B1, GABA_B2, Gα_o, Gβ5, and RGS7 revealed their progressive enrichment around excitatory synapses on dendritic spines of CA1 pyramidal cells toward P15. At presynaptic sites, GABA_B receptors colocalize with Ca_V2.1, Gα_o, Gβ5, and RGS7 in the active zone and extrasynaptic membranes of axon terminals, establishing synapses on dendritic spines of CA1 pyramidal cells. In the cerebellum, double immunofluorescence at P7 and P10 revealed the colocalization of GABA_B1 and Ca_V2.1 in the whole dendritic tree of developing Purkinje cells. Immunoelectron microscopy at P15 showed that GABA_B1, GABA_B2, Ca_V2.1, Gα_o, Gβ5, and RGS7 are distributed along the dendritic surface of Purkinje cells, enriched close to excitatory synapses in spines. Altogether, these data suggest that macromolecular complexes composed of GABA_B1/GABA_B2/Ca_V2.1/Gα_o/Gβ5/RGS7 are pre-assembled during key stages of postnatal development in hippocampal and cerebellar neurons.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18970"},"PeriodicalIF":2.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncocytic salivary gland carcinomas.","authors":"Ziyad Alsugair, Anne Champagnac, Nazim Benzerdjeb","doi":"10.14670/HH-18-969","DOIUrl":"https://doi.org/10.14670/HH-18-969","url":null,"abstract":"<p><p>Oncocytic carcinomas of the salivary glands represent a rare and diverse group of malignancies characterised by granular eosinophilic cytoplasm due to abundant mitochondria. This review provides a comprehensive overview of oncocytic salivary gland carcinomas, categorised by their morphological patterns: monophasic, biphasic, and complex. Monophasic entities include oncocytic intraductal carcinoma (OIDC), oncocytic salivary duct carcinoma (OSDC), acinic cell carcinoma (ACC), and secretory carcinoma (SC). These tumours vary significantly in histological architecture, immunohistochemical profiles, and genetic alterations, ranging from <i>TRIM33::RET</i> fusions and <i>BRAF</i> V600E mutations in OIDC to <i>NR4A3</i> rearrangements in ACC and <i>ETV6::NTRK3</i> fusions in SC. Biphasic tumours, such as oncocytic epithelial-myoepithelial carcinoma (OEMC) and oncocytic adenocarcinoma not otherwise specified (OANOS), further complicate diagnosis due to dual cellular composition and overlapping features with other neoplasms. Complex-pattern tumours, particularly oncocytic mucoepidermoid carcinoma (OMEC), highlight diagnostic challenges and underscore the need for advanced molecular diagnostics. This article emphasises the critical role of integrated histopathological examination, immunohistochemical staining, and molecular profiling in the accurate classification of these neoplasms. Despite diagnostic advancements, some entities, like OANOS, remain provisional, pending widespread access to transcriptomic tools. Recognising the molecular heterogeneity and clinicopathologic nuances of oncocytic carcinomas is essential for improving diagnostic precision, prognostication, and guiding targeted therapy.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18969"},"PeriodicalIF":2.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of the protective effect of 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside on MPTP-induced Parkinson's disease mice.","authors":"Gang Wu, Xiaolin Dong, Qingyun Li, Yanping Li, Furong Jin, Jingting Lu, Chengda Han, Lianbing Lin","doi":"10.14670/HH-18-968","DOIUrl":"https://doi.org/10.14670/HH-18-968","url":null,"abstract":"<p><strong>Background and purpose: </strong>Parkinson's disease (PD) is a common neurodegenerative disorder with a complex pathogenesis. 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) is one of the main active components of <i>Polygonum multiflorum</i> Thunb., which has therapeutic effects in various neurodegenerative diseases. The aim of this study was to explore the influence of TSG on the PD process.</p><p><strong>Methods: </strong>The PD mouse model was constructed via the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD process was evaluated via behavioral tests, HE staining, immunohistochemistry, and immunofluorescence. The levels of related proteins and inflammatory factors were detected via western blotting and ELISA. The effect of TSG on the intestinal flora of MPTP-induced PD mice was evaluated through 16S rDNA sequencing.</p><p><strong>Results: </strong>TSG intervention can significantly alleviate motor dysfunction in PD mice, increase the number of TH-positive neurons in the substantia nigra, inhibit the accumulation of α-syn and glial cell activation, reduce the expression of the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and COX2 proteins in the substantia nigra and colon, inhibit neuroinflammation and intestinal inflammation, decrease the levels of LPS, LBP, TNF-α, IL-1β, and IL-6 in the serum, suppress systemic inflammation, reduce damage to the blood-brain barrier (BBB) and intestinal barrier in PD mice, and restore species diversity and abundance of the intestinal flora in PD mice to a certain extent.</p><p><strong>Conclusion: </strong>TSG can improve motor coordination ability, systemic and neuroinflammatory levels, BBB injury, intestinal barrier injury, and the intestinal flora composition of PD mice, suggesting that TSG has a protective effect on MPTP-induced PD mice.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18968"},"PeriodicalIF":2.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric neoplasm with foveolar-cell differentiation in <i>Helicobacter pylori</i>-naïve patients.","authors":"Satoshi Kotani, Kotaro Shibagaki, Ryoji Kushima, Tsuyoshi Mishiro, Kenichi Kishimoto, Yusuke Takahashi, Norihisa Ishimura, Asuka Araki, Mamiko Nagase, Daisuke Niino, Shunji Ishihara","doi":"10.14670/HH-18-966","DOIUrl":"https://doi.org/10.14670/HH-18-966","url":null,"abstract":"<p><p>The incidence of <i>Helicobacter pylori (Hp)</i>-naïve gastric neoplasms (HpNGNs) is increasing due to a growing <i>Hp</i>-naïve population and improved recognition. Among these, HpNGNs that predominantly exhibit foveolar-cell differentiation include foveolar-type gastric adenomas (FGA) and fundic gland polyps with dysplasia (FGPD). Traditionally, FGAs have been considered large, whitish, flat lesions (flat-type FGA), primarily associated with syndromic conditions, such as familial adenomatous polyposis (FAP) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), while sporadic cases are rare. This type exhibits a gastric immunophenotype with diverse differentiation, mainly toward foveolar cells, and harbors APC and KRAS mutations in all sporadic and most syndromic cases. A distinct subset of FGAs, termed foveolar-type gastric adenoma with a raspberry-like appearance (FGA-RA), has been identified. It presents as small, reddish polyps with unique macroscopic and microscopic features and only occurs sporadically. FGA-RA often mimics gastric hyperplastic polyps macroscopically and typically exhibits low-grade dysplasia, making biopsy-based diagnosis challenging and leading to its historical underrecognition. It shows pure foveolar differentiation and consistently harbors Krüppel-like factor 4 (KLF4) mutations. FGPD primarily develops sporadically in <i>Hp</i>-naïve individuals with long-term proton pump inhibitor use. A syndromic form, resembling flat-type FGAs, is also associated with FAP and GAPPS. Histologically, FGPD features dysplasia confined to the superficial foveolar epithelium and mucus neck cells overlying fundic gland polyps, with APC mutations detected in approximately 50% of cases. This review explores the clinicopathological and molecular characteristics of HpNGNs with predominant foveolar cell differentiation, emphasizing the need for an updated histological diagnostic framework.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18966"},"PeriodicalIF":2.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NeuN expression in health and disease: A histological perspective on neuronal heterogeneity.","authors":"Joongbum Moon, Ji Hyeon Ahn, Moo-Ho Won","doi":"10.14670/HH-18-965","DOIUrl":"https://doi.org/10.14670/HH-18-965","url":null,"abstract":"<p><p>Neuronal nuclei (NeuN), also known as Rbfox3, is a widely used neuronal marker for identifying postmitotic neurons in both basic neuroscience and diagnostic neuropathology. Since its discovery, NeuN immunoreactivity has enabled accurate neuron counting, injury assessment, and anatomical mapping. However, accumulating evidence demonstrates that NeuN is not universally expressed across all mature neurons. Specific neuron types, such as olfactory mitral cells, cerebellar Purkinje cells, and retinal photoreceptors, consistently lack NeuN immunostaining despite functional maturity. Moreover, NeuN expression is dynamically regulated under pathological conditions. In ischemia-reperfusion (I/R) injury, neurodegenerative diseases (e.g., Alzheimer's and Parkinson's), and traumatic brain injury or epilepsy-selected for their representative diversity in pathophysiological stress (ischemic, degenerative, and mechanical)-NeuN downregulation may reflect functional compromise, stress responses, or reversible transcriptional changes rather than irreversible cell loss. These findings highlight the limitations of interpreting NeuN negativity as neuronal death. This review synthesizes recent findings on NeuN expression patterns, molecular mechanisms regulating its presence or absence, and the implications for research and diagnosis. We propose that NeuN should not be regarded as a binary marker but rather as a dynamic indicator of neuronal state. Multi-marker strategies and molecular tools such as spatial transcriptomics and RNA sequencing are suggested to improve the resolution of neuronal analysis. As histological and transcriptomic approaches converge, NeuN's role will likely expand from a structural identifier to a contextual readout of neuronal integrity and function.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18965"},"PeriodicalIF":2.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}