Histology and histopathology最新文献

{"title":"Wnt5a regulates the expression of developmental genes in the adult retina following optic nerve crush injury.","authors":"Gabrielle A Albano, Paola E Parrales, Abigail S Hackam","doi":"10.14670/HH-18-896","DOIUrl":"https://doi.org/10.14670/HH-18-896","url":null,"abstract":"<p><p>Canonical and non-canonical Wnt signaling pathways are well-characterized regulators of retinal development. Wnt signaling also promotes neuroprotection and regeneration in adult tissues, including retinal ganglion cell (RGC) survival and axonal regrowth after optic nerve injury. However, it is unknown whether Wnt-dependent neuroprotection after injury in the adult CNS is associated with altered expression of developmental genes. Muller glia are a prominent radial glia type in the retina that play critical roles in retinal neuron protection, RGC neurite growth, and axon regeneration by acting through Wnt and other signaling pathways. We recently used mass spectrometry to characterize proteins secreted from Muller glia in response to Wnt signaling. In this study, we investigated whether the Wnt-induced Muller glia secretome includes proteins involved in development and whether their corresponding genes are regulated by Wnt5a during axonal regeneration in a mouse model of optic nerve crush (ONC) injury. Adult mice received intravitreal injections of Wnt5a or saline at the time of ONC injury, and then retina tissue was collected at early time points post-injury. The expression of candidate Wnt-regulated developmental genes and related proteins were characterized by qPCR and immunohistochemistry. Our findings revealed that Wnt5a downregulated the expression of specific developmental genes, including cilia-related genes <i>Nphp4, INTU</i>, and <i>Jade1</i>, as well as transcriptional regulators <i>Pax6</i> and <i>Tsc1</i>, with time-dependent changes observed during axonal regrowth. Several of these genes were localized to RGCs and inner nuclear layer cells, suggesting direct effects in RGCs and contributions from Muller glia. These results demonstrate that specific developmental gene pathways are suppressed by Wnt5a in association with RGC survival and axon regrowth following injury. Therefore, this study adds to our knowledge of potential mechanisms of Wnt-mediated optic nerve regeneration and identifies new categories of putative regeneration-regulating genes for further study.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18896"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614798","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":"The prognostic value of adipokine receptors leptinR and adiponectinR1 in obesity-inducible solid tumours.","authors":"Isabella Bollen, Marit Bernhardt, Thore Thiesler, Franziska Isabelle Winterhagen, Andreas Türler, Manuel Ritter, Alexander Mustea, Glen Kristiansen","doi":"10.14670/HH-18-895","DOIUrl":"10.14670/HH-18-895","url":null,"abstract":"<p><strong>Background: </strong>With the rising incidence of life expectancy, obesity, and tumours, understanding the incretory influence of adipose tissue in tumorigenesis becomes increasingly important. As the adipokines leptin and adiponectin are released by fat tissue, we aimed to analyse the expression of their respective receptors in tumours for which an association with obesity is epidemiologically hypothesised.</p><p><strong>Methods: </strong>The expression of leptinR and adipoR1 were analysed in cohorts of renal cell cancer (n=391), cervical cancer (n=155), vulvar cancer (n=107), and endometrial cancer (n=90) by immunohistochemistry and correlated with clinicopathological parameters including survival times.</p><p><strong>Results: </strong>Expression of leptinR was high in renal cell cancer (62.2% of cases), vulvar carcinoma (50%), and endometrial cancer (80.5% of tissue-samples). High expression was associated with favourable clinicopathological markers and longer overall survival times in renal cell and vulvar cancer. AdipoR1 was only weakly expressed in all four tumour entities and did not show significant associations with clinicopathological parameters or prognosis.</p><p><strong>Conclusion: </strong>High leptinR is a promising biomarker of favourable tumour outcomes in renal cell carcinoma and vulvar carcinoma.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18895"},"PeriodicalIF":2.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604720","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":"NTRK protein expression in NSCLC and its clinicopathological correlation.","authors":"Jair Gutierrez-Herrera, M Angeles Montero-Fernandez, Luigi De Petris, Ricardo Guijarro, Simon Ekman, Cristian Ortiz-Villalón","doi":"10.14670/HH-18-894","DOIUrl":"10.14670/HH-18-894","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a complex disease with diverse clinical and molecular characteristics. Since the discovery of the oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusion in colorectal cancer in 1986, its understanding has gradually progressed. NTRK's relevance is crucial to understanding some tumor development and how specific tyrosine receptor kinase inhibitors (TRKI) work. <i>NTRK1, NTRK2,</i> and <i>NTRK3</i> (encoding the neurotrophin receptors TRKA, TRKB, and TRKC, respectively) rearrangement induces high tumor transforming ability. This study investigates the clinical relevance of NTRK immunohistochemistry in NSCLC patients in a cohort of 482 patients from Karolinska University Hospital with detailed clinical and pathological studies. Immunohistochemical staining for NTRK expression was performed, and the results were correlated with patient demographics, histological subtypes, tumor extent, and staging. Our findings revealed that NTRK expression, predominantly membranous and cytoplasmic, was detected in 22 out of 482 cases (4.56%). Notably, NTRK expression was more frequently observed in squamous-cell carcinoma (SqCC) than in adenocarcinoma (AdCa). Clinical correlations indicated a significant association between NTRK expression and histologic subtypes (<i>p</i><0.001) and grade of differentiation (<i>p</i>=0.036). However, no significant correlations were observed with age, sex, tumor size, staging, or OS. NTRK immunohistochemistry represents a potential biomarker for a subset of NSCLC patients, particularly those with SqCC histology. Understanding the clinical implications of NTRK expression may contribute to personalized treatment strategies in NSCLC.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18894"},"PeriodicalIF":2.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596806","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":"Pinocembrin ameliorates non-alcoholic fatty liver disease by activating Nrf2/HO-1 and inhibiting the NF-κB signaling pathway.","authors":"Weina Chen, Diming Xue, Xia Feng, Yinhang Zhong, Quanqing Li, Weihang Zhang, Guojun Jiang","doi":"10.14670/HH-18-893","DOIUrl":"https://doi.org/10.14670/HH-18-893","url":null,"abstract":"<p><strong>Objectives: </strong>The high intake of high-fat diets and changes in sedentary lifestyles have led to an increase in non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effect and mechanism of Pinocembrin (Pin) on NAFLD <i>in vivo</i> and <i>in vitro</i>.</p><p><strong>Methods: </strong>The pharmacodynamics of Pin alone or in combination with ML385 was assessed in high-fat diet (HFD)-mediated NAFLD mice. HepG2 cells were treated with palmitic acid (PA)/oleic acid (OA) (1:2) as an <i>in-vitro</i> model to study the effect of Pin on lipid deposition and oxidative stress. The roles of Pin in glucose and lipid metabolism, inflammation, oxidative stress, and the Nrf2/HO-1/NF-κB pathway were measured.</p><p><strong>Results: </strong>Pin alleviated lipid deposition, inflammatory response, and oxidative stress in HFD-induced NAFLD mice and PA/OA-induced HepG2 cells. Moreover, ML385 partly attenuated the protection of Pin on inflammatory response and oxidative stress <i>in vivo</i> and <i>in vitro</i>. More importantly, feeding with an HFD significantly decreased the expression of Nrf2 and HO-1, but treatment with Pin increased their expression, accompanied by an increased nuclear transposition of Nrf2.</p><p><strong>Conclusion: </strong>Taken together, these results indicated that Pin alleviated glucose and lipid metabolism disorders, inflammation, and oxidative stress in NAFLD by activating the Nrf2/HO-1 signaling pathway and restraining the NF-κB pathway.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18893"},"PeriodicalIF":2.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585544","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":"Chelerythrine-mediated targeting of NF-κB and Nrf2 pathways alleviates liver injury in a carbon tetrachloride-induced liver fibrosis mouse model.","authors":"Yisong Ding, Xiaoming Li, Ruixing Qi, Yingshi Su, Xiaoli Wang","doi":"10.14670/HH-18-892","DOIUrl":"10.14670/HH-18-892","url":null,"abstract":"<p><strong>Background and aims: </strong>This study aimed to investigate the mechanism and efficacy of chelerythrine (CHE) in treating carbon tetrachloride (CCl₄)-induced liver fibrosis, with a particular focus on the nuclear factor-erythroid-related factor-2 (Nrf2) and nuclear factor-kappa-B (NF-κB) signaling pathways.</p><p><strong>Methods: </strong>Mice were induced with CCl₄ for eight weeks and categorized into the control group, CCl₄ model group, and CHE low (7 mg/kg/d, ig,), medium (14 mg/kg/d, ig), and high-dose (28 mg/kg/d, ig) groups with 10 animals in each group. Following CHE treatment, liver sample morphology was assessed using multiple immunohistochemistry, and serum biochemical indicators were measured. ELISA was used to determine IL-10, IL-1β, and TNF-α contents. Western blotting and RT-PCR were employed to analyze protein and mRNA levels of α-SMA, Col-I, fibronectin, Nrf2, HO-1, NQO1, GCLc, GCLm, NF-κB, p-NF-κB, IκBα, and p-IκBα. Nrf2 knockout mice were used to assess the impact of CHE on the Nrf2 signaling pathway.</p><p><strong>Results: </strong>The findings demonstrated that CHE significantly ameliorated oxidative damage, inflammatory response, and liver fibrosis in CCl₄-induced mice. CHE treatment increased Nrf2 expression and its target proteins, including HO-1 and GCLc, an effect not observed in Nrf2 knockout mice. In addition, CHE reduced NF-κB expression levels.</p><p><strong>Conclusions: </strong>These results suggest that CHE can alleviate liver fibrosis in CCl₄-induced mice by modulating NF-κB/IκBα and Nrf2 signaling pathways. These findings propose CHE as a potential novel anti-liver fibrosis drug.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18892"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572941","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":"Adaptive changes in the visual cortex after photoreceptor degeneration in retinitis pigmentosa.","authors":"Juan R Martinez-Galan, Elena Caminos","doi":"10.14670/HH-18-891","DOIUrl":"https://doi.org/10.14670/HH-18-891","url":null,"abstract":"<p><p>Retinitis pigmentosa (RP) is a group of hereditary disorders that cause progressive retinal degeneration, affecting the rods and, subsequently, the cones, which results in progressive vision loss. RP is genetically heterogeneous and is inherited in an autosomal dominant, autosomal recessive, X-linked, or sporadic non-Mendelian manner. The recent advancements in repairing damaged retinas highlight the necessity of understanding the impact of photoreceptor degeneration on the visual cortex. This is because functional vision may not be adequately restored if this region is significantly impaired prior to treatment. In the present review, we have analyzed the rodent models of RP that have been most frequently used and the physiological and morphological changes occurring in both humans and rodents with this disorder. Following visually evoked stimulation, the processing of visual information in the primary visual cortex (V1) of individuals with RP is altered due to modifications in the transduction of the signal originating in the degenerated retina. Moreover, alterations in the intrinsic electrophysiological properties of cortical neurons and neural circuits have also been documented. Finally, several neurochemical and/or morphological changes are observed in synaptic structures associated with pyramidal neurons and in select inhibitory interneurons. Nevertheless, despite the physiological and morphological changes that have been described, the impact of RP on the visual cortex does not inevitably result in irreversible damage, as the alterations do not appear to be particularly severe. Brain plasticity is more restricted in adults; however, remodeling of the visual cortex in mice and humans is possible, which encourages further work on therapies capable of partially restoring the lost visual function.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18891"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566933","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":"The role of neutrophils and their immunosuppressive effects on prostate cancer.","authors":"Yihaoyun Lou, Zhiguo Fan, Shancheng Ren","doi":"10.14670/HH-18-890","DOIUrl":"https://doi.org/10.14670/HH-18-890","url":null,"abstract":"<p><p>Over the past decade, there has been a significant increase in the incidence of prostate cancer on a global scale, establishing it as the second most prevalent malignant tumor among European and American males. Neutrophils are myeloid immune cells that constitute a crucial proportion of inflammatory cells within the human circulatory system and actively contribute to the composition of the prostate tumor microenvironment (TME). Recent investigations have revealed that neutrophils are influenced by the surrounding tumor environment and possess a dual capacity to either promote or suppress cancer within the TME. Nevertheless, the precise mechanisms of neutrophils in prostate cancer remain inadequately elucidated. In this review, we aimed to comprehensively outline the character of neutrophils in the development and progression of prostate cancer while also exploring the clinical prognostic significance of the neutrophil-to-lymphocyte ratio (NLR).</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18890"},"PeriodicalIF":2.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556731","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":"Suppressive role of fukutin on cell proliferation in uterine cervical carcinoma in relation to Aurora-A kinase.","authors":"Tomoko Yamamoto, Yukinori Okamura, Yoichiro Kato, Kenta Masui, Yoji Nagasima, Atsushi Kurata","doi":"10.14670/HH-18-889","DOIUrl":"https://doi.org/10.14670/HH-18-889","url":null,"abstract":"<p><p><i>Fukutin</i>, the gene responsible for Fukuyama congenital muscular dystrophy (FCMD), is involved in the glycosylation of α-dystroglycan (α-DG). On the other hand, fukutin is expressed in various organs, and the roles of fukutin in non-neuromuscular tissues are not fully elucidated. In the present immunohistochemical study of uterine cervical carcinoma, Ki-67-positive cells tended to be more in areas showing weaker expression of fukutin. In HeLa cells, Ki-67-positive cells were increased after the suppression of fukutin by RNAi, and were decreased by overexpression of fukutin. Similar results were obtained upon phosphorylation of histone H3 at serine 10, which is enriched during mitosis. Interestingly, Aurora-A kinase (AURKA), one of the proteins regulating Ser10 phosphorylation of histone H3, was highly expressed in HeLa cells, and the phosphorylation of AURKA was reduced by overexpression of fukutin. Furthermore, fukutin is co-localized with targeting protein for Xklp2 (TPX2), a protein enhancing AURKA activity. Fukutin may be able to suppress cell proliferation by reducing AURKA phosphorylation, probably competing with TPX2.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18889"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541781","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":"Advantages and limitations of 3,3',5,5'-tetramethylbenzidine for immunohistochemical staining.","authors":"Chao Yu, Xiao Liu, Peiyuan Zhao, Zhidong Sun, Yurong Song, Yuan Cao, Ming Cheng","doi":"10.14670/HH-18-888","DOIUrl":"https://doi.org/10.14670/HH-18-888","url":null,"abstract":"<p><p>In this study, two chromogenic systems, horseradish peroxidase (HRP)-3,3'-diaminobenzidine (DAB) and HRP-3,3',5,5'-tetramethylbenzidine (TMB), were used to perform single-color and double-color immunohistochemical staining (sIHC and dIHC, respectively) on multiple antigens in four distinct tissue types. The chromogenic results of the HRP-TMB system exhibited a vibrant blue-green color, and the tissue localization and signal intensity were consistent with those of the HRP-DAB system. In addition, it demonstrated clear differentiation from the hematoxylin-stained nucleus, endogenous melanin, and brown chromogenic results of HRP-DAB. TMB staining in tissues that contain high endogenous pigment levels eliminates the need for melanin bleaching, thereby facilitating direct observation and potentially improving the detection speed and interpretation. TMB can also be used in combination with DAB for dIHC, thus allowing detection of the two markers on a single slide. However, the TMB staining results are not stable over the long term and require image storage using slide scanners, thereby limiting its application. Additionally, in dIHC, overlapping signals of the first marker may obscure the second marker, potentially leading to bias or false negatives. Therefore, careful consideration is required when designing dIHC detection systems. Based on the above, we propose that TMB is a valuable supplement to DAB for immunohistochemical staining and deserves further promotion and utilization. However, additional research is needed to improve the composition of TMB chromogenic reagents, prolong the longevity of staining results, and overcome current limitations.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18888"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523335","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":"Genomic features of bladder neuroendocrine carcinoma with composite histology.","authors":"Akihiro Ohmoto, Keiichiro Kitahama, Yasuyuki Shigematsu, Naomi Hayashi, Junji Yonese, Kentaro Inamura, Shunji Takahashi","doi":"10.14670/HH-18-887","DOIUrl":"https://doi.org/10.14670/HH-18-887","url":null,"abstract":"<p><p>Neuroendocrine carcinoma (NEC) is a rare and aggressive malignancy derived from multiple body parts, with the urogenital organs being the second-largest extrapulmonary sites. The detailed mechanism of bladder NEC pathogenesis remains unknown. We reviewed data from 23 patients diagnosed with NEC from urogenital organs (bladder and prostate) and conducted targeted sequencing of 523 cancer-related genes, focusing on bladder NEC. While 14 cases featured a pure NEC histology, the remaining nine cases included NEC histology mixed with other tumors, such as urothelial carcinoma (UC) or adenocarcinoma. Median overall survival in the entire cohort was 11.1 months, and survival curves were comparable between pure NEC and NEC of mixed appearance. Major mutations detected in the NEC component were in <i>TP53</i> (38%), <i>TERT</i> promoter (31%), <i>PIK3CA</i> (25%), histone-modification genes (19%), and <i>RB1</i> (19%). The <i>BARD1</i> frameshift variant related to homologous recombination was also detected in one patient. More than half of the patients had a high total mutational burden (TMB; ≥10), including two with a TMB ≥45. Intriguingly, at least one identical gene variant in driver genes was detected between NEC and non-NEC (UC) components in the four bladder specimens analyzed. These results highlight the possibility of shared genetic background between bladder NEC and UC. Additionally, several cases harbored druggable gene alterations as presented by TMB-high. Our presentation of the histopathological and molecular features of NEC may help clarify the underlying mechanisms and contribute to efficient treatment of the disease.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18887"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515382","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}