Histochemistry and Cell Biology最新文献

FOXM1 requires IDH1 for late genes expression in mitotic cells. FOXM1 需要 IDH1 才能在有丝分裂细胞中表达晚期基因。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-07-22 DOI: 10.1007/s00418-024-02307-8

Balabhaskararao Kancharana, Hashnu Dutta, Nishant Jain

引用次数: 0

Expression of mRNA for molecules that regulate angiogenesis, endothelial cell survival, and vascular permeability is altered in endothelial cells isolated from db/db mouse hearts. 在分离自 db/db 小鼠心脏的内皮细胞中，调节血管生成、内皮细胞存活和血管通透性的分子 mRNA 的表达发生了改变。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-09-24 DOI: 10.1007/s00418-024-02327-4

Krzysztof Bartkowiak, Mateusz Bartkowiak, Ewa Jankowska-Steifer, Anna Ratajska, Elżbieta Czarnowska, Marek Kujawa, Olga Aniołek, Justyna Niderla-Bielińska

{"title":"Expression of mRNA for molecules that regulate angiogenesis, endothelial cell survival, and vascular permeability is altered in endothelial cells isolated from db/db mouse hearts.","authors":"Krzysztof Bartkowiak, Mateusz Bartkowiak, Ewa Jankowska-Steifer, Anna Ratajska, Elżbieta Czarnowska, Marek Kujawa, Olga Aniołek, Justyna Niderla-Bielińska","doi":"10.1007/s00418-024-02327-4","DOIUrl":"10.1007/s00418-024-02327-4","url":null,"abstract":"Metabolic syndrome (MetS) is a condition that includes symptoms, such as obesity, hyperglycemia, and hypertension, which elevate cardiovascular risk. An impaired angiogenic response of endothelial cells (ECs) in heart and peripheral organs has been proposed in MetS, but the mechanisms of this phenomenon have not been thoroughly explored. Results obtained from evaluating the whole myocardium are inconsistent, since different types of cells react differently to MetS environment and a variety of molecular pathways are involved in the angiogenic response. Therefore, the aim of this paper was to study one selected pathway-the VEGF/VEGFR pathway, which regulates the angiogenic response and microvascular permeability in ECs isolated from db/db mouse hearts. The expression of mRNAs for VEGF/VEGFR axis proteins was assessed with RT-PCR in ECs isolated from control and db/db mouse myocardium. The density of CD31-, VEGFR2-, and VE-cadherin-positive cells was examined with confocal microscopy, and the ultrastructure of ECs was analyzed with transmission electron microscopy. The aortic ring assay was used to assess the capacity of ECs to respond to angiogenic stimuli. Our results showed a decreased number of microvessels, diminished expression of VE-cadherin and VEGFR2 and widened gaps between the ECs of microcapillaries. The aortic ring assay showed a diminished number of sprouts in db/db mice. These results may indicate that ECs in MetS enhance the production of mRNA for VEGF/VRGFR axis proteins, yet sprout formation and vascular barrier maintenance are limited. These novel data may provide a foundation for further studies on ECs dysfunction in MetS.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"523-539"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte. 通过影响减数分裂卵母细胞中细胞周期蛋白B1和Securin的稳定，MEIKIN的表达及其C端被PLK1磷酸化与分裂期-无丝分裂过渡期密切相关。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-08-02 DOI: 10.1007/s00418-024-02316-7

Li-Hua Fan, Shu-Tao Qi, Zhen-Bo Wang, Ying-Chun Ouyang, Wen-Long Lei, Yue Wang, Ang Li, Feng Wang, Jian Li, Li Li, Yuan-Yuan Li, Yi Hou, Heide Schatten, Wei-Hua Wang, Qing-Yuan Sun, Xiang-Hong Ou

{"title":"MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.","authors":"Li-Hua Fan, Shu-Tao Qi, Zhen-Bo Wang, Ying-Chun Ouyang, Wen-Long Lei, Yue Wang, Ang Li, Feng Wang, Jian Li, Li Li, Yuan-Yuan Li, Yi Hou, Heide Schatten, Wei-Hua Wang, Qing-Yuan Sun, Xiang-Hong Ou","doi":"10.1007/s00418-024-02316-7","DOIUrl":"10.1007/s00418-024-02316-7","url":null,"abstract":"Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"447-464"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874677","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}

引用次数: 0

Expression of SARS-CoV-2 entry molecules ACE2, NRP1, TMPRSS2, and FURIN in the reproductive tissues of male macaques. 雄性猕猴生殖组织中 SARS-CoV-2 进入分子 ACE2、NRP1、TMPRSS2 和 FURIN 的表达。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-08-17 DOI: 10.1007/s00418-024-02314-9

Ryutaro Moriyama, Sho Nakamura, Ikki Mitsui, Makoto Sugiyama, Hirotaka Fukui, Hitomi Fukui, Teruki Hagiwara, Takako Miyabe-Nishiwaki, Juri Suzuki

{"title":"Expression of SARS-CoV-2 entry molecules ACE2, NRP1, TMPRSS2, and FURIN in the reproductive tissues of male macaques.","authors":"Ryutaro Moriyama, Sho Nakamura, Ikki Mitsui, Makoto Sugiyama, Hirotaka Fukui, Hitomi Fukui, Teruki Hagiwara, Takako Miyabe-Nishiwaki, Juri Suzuki","doi":"10.1007/s00418-024-02314-9","DOIUrl":"10.1007/s00418-024-02314-9","url":null,"abstract":"Coronavirus disease 2019 (COVID-19) reportedly affects male reproductive function by causing spermatogenesis dysfunction and suppressing testosterone secretion. However, the relationship between COVID-19 and impaired reproductive function, such as whether these effects on reproductive function are a direct effect of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in male reproductive organs or an indirect effect of high fever, is not known. Here, we examined whether the cell entry molecules of SARS-CoV-2, namely, ACE2, NRP1, TMPRSS2, and FURIN, are expressed in the male reproductive organs using the testes and accessory gonads of macaques during the breeding season. RT-PCR expression analysis showed that the testes alone expressed all four molecules. Immunohistochemical staining of testis tissue sections revealed that ACE2 is expressed in Leydig cells and the apical region of Sertoli cells, whereas NRP1 is expressed in the cell bodies surrounding the Leydig and Sertoli cell nuclei. FURIN is mainly expressed in Leydig cells, secondary spermatocytes, and spermatids. However, TMPRSS2 immunopositive cells were not observed. Therefore, it was not possible to observe cells expressing all four molecules in the gonads and accessory gonads of male primates. These results suggest that SARS-CoV-2 is unlikely to directly affect spermatogenesis in primates or proliferate in cells of the seminiferous tubules and undergo release into the semen through the previously known ACE2-mediated infection route. However, the expression of three molecules, including ACE2, was observed in Leydig cells, suggesting that testosterone synthesis and secretion may be affected when primates, including humans, are infected with SARS-CoV-2.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"465-475"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995686","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}

引用次数: 0

Be bold, start cold! cold formalin fixation of colorectal cancer specimens granted superior DNA and RNA quality for downstream molecular analysis. 大胆尝试，从冷冻开始！冷福尔马林固定结直肠癌标本可为下游分子分析提供优质的 DNA 和 RNA。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-09-24 DOI: 10.1007/s00418-024-02326-5

Ennio Nano, Alessandro Gambella, Michele Paudice, Anna Garuti, Simona Pigozzi, Luca Valle, Federica Grillo, Luca Mastracci

{"title":"Be bold, start cold! cold formalin fixation of colorectal cancer specimens granted superior DNA and RNA quality for downstream molecular analysis.","authors":"Ennio Nano, Alessandro Gambella, Michele Paudice, Anna Garuti, Simona Pigozzi, Luca Valle, Federica Grillo, Luca Mastracci","doi":"10.1007/s00418-024-02326-5","DOIUrl":"10.1007/s00418-024-02326-5","url":null,"abstract":"The use of cold formalin fixation (CFF; i.e., fixating tissue samples with 4 °C precooled formalin) recently attracted further attention owing to its putative improved ability to preserve nucleic acid compared with standard room temperature formalin (SFF). In this study, we aimed to assess the effect of four formalin-based fixation protocols (SFF, CFF, delayed formalin fixation-DFF, and cold formalin hyperfixation; CFH) on both DNA and RNA quality. We collected 97 colorectal cancer (CRC) and analyzed 23 metrics of nucleic acid quantity and quality yield using a multiplatform approach by combining spectrophotometric, fluorimetric, electrophoretic, and polymerase chain reaction (PCR) assays. Following confirmation of fixation-protocol-related different effects via clustering analysis, CFF presented best metrics compared with all protocols, specifically positive coefficients of DV1000-60000, DV2/DV1, DNA λ ratio 260/230, and ABL gene expression absolute copies, and negative coefficient of DV150-1000. The SFF subgroup presented a positive coefficient of DV150-1000 and negative coefficients for DV1000-60000, DV2/DV1, RNA λ ratio 260/230, RNA QuBit concentration, DV100/200, RNA electrophoresis concentration and absolute quantity, and ABL copies. Overall, we confirmed the superior yield performances of CFF preservation for both DNA and RNA compared with the other protocols in our series of CRC samples. Pending further validations and clarification of the specific mechanisms behind these findings, our study supports the implementation of CFF in the pathology unit routine specimen management for tumor tissue molecular profiling.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"541-550"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Specificity of widely used lectins as probed with oligosaccharide and plant polysaccharide arrays. 用寡糖和植物多糖阵列探测广泛使用的凝集素的特异性。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-08-25 DOI: 10.1007/s00418-024-02323-8

Nadezhda V Shilova, Oxana E Galanina, Svetlana M Polyakova, Alexey Yu Nokel, Galina V Pazynina, Victoria V Golovchenko, Olga A Patova, Polina V Mikshina, Tatayana A Gorshkova, Nicolai V Bovin

{"title":"Specificity of widely used lectins as probed with oligosaccharide and plant polysaccharide arrays.","authors":"Nadezhda V Shilova, Oxana E Galanina, Svetlana M Polyakova, Alexey Yu Nokel, Galina V Pazynina, Victoria V Golovchenko, Olga A Patova, Polina V Mikshina, Tatayana A Gorshkova, Nicolai V Bovin","doi":"10.1007/s00418-024-02323-8","DOIUrl":"10.1007/s00418-024-02323-8","url":null,"abstract":"Glycan-binding specificity was studied for Jacalin, RCA 120, SBA, PHA-L, PHA-E, WGA, UEA, AAL, LTL, LEL, SNA, DSA, LCA, MAH and Con A, lectins widely used in histochemistry. Oligosaccharide- and polysaccharide-based glycan arrays were applied. Expected specificity was confirmed for only 6 of the 15 lectins and the glycan binding profiles of some lectins were dramatically broader than generally accepted. WGA, LEL and DSA known as chitooligosaccharide-specific, were unexpectedly polyreactive, binding to other glycans with the same affinity as to chitobiose, ABH antigens and oligolactosamines (unsubstituted and sialylated). SBA, in addition to expected binding to glycans with terminal GalNAcα, also had high affinity for the GM1 ganglioside. MAH demonstrated much higher affinity to a variety of sulfated glycans compared to Neu5Acα2-3Galβ1-3GalNAcα. Contrary to the common view, LCA demonstrated the maximum binding to (GlcNAcβ1-2Manα1)2-3,6-Manβ1-4GlcNAcβ1-4GlcNAc N-glycan, while it had no interaction with corresponding Gal or Neu5Ac terminated versions. This observed polyreactivity of some lectins casts doubt on their use in accurately determining the presence of a specific glycan structure by histochemical studies. However, comparisons of sera from healthy and diseased individuals with help of a lectin array can easily establish differences in glycosylation patterns and presumptive glycan identities, which can later be clarified using more accurate methods of structural analysis.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"495-510"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055463","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}

引用次数: 0

Identification and culture of functional salivary gland ductal epithelial cells. 功能性唾液腺导管上皮细胞的鉴定和培养。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-08-29 DOI: 10.1007/s00418-024-02324-7

Han-Shu Zhang, You-Wei Zhao, Xin-Yi Tao, Xin Cong, Li-Ling Wu, Guang-Yan Yu, Yan Zhang

{"title":"Identification and culture of functional salivary gland ductal epithelial cells.","authors":"Han-Shu Zhang, You-Wei Zhao, Xin-Yi Tao, Xin Cong, Li-Ling Wu, Guang-Yan Yu, Yan Zhang","doi":"10.1007/s00418-024-02324-7","DOIUrl":"10.1007/s00418-024-02324-7","url":null,"abstract":"Sialadenitis is a prevalent salivary gland disease resulting in decreased salivary flow rate. To date, little is known about the exact changes and mechanism of ductal cells in sialadenitis. This study aims to establish an efficient method to identify and isolate ductal cells, thereby facilitating further research on this specific cell type. Immunofluorescence for cytokeratin 13 and cytokeratin 19 was conducted in salivary glands to confirm their specificity as ductal cell markers. The dissected ducts were assessed through PCR and Western blot of cytokeratin 19 and digested by dispase and collagenase. The functionality of the isolated ductal cells was determined by measuring intracellular calcium. Cytokeratin 19 and cytokeratin 13 were expressed in all segments of human ducts. Cytokeratin 19 was limited to ducts excluding granular convoluted tubules in rat and mouse. The purities of the obtained ductal cells were approximately 98% in humans and 93% in rats. Furthermore, intracellular free calcium increased with time and concentration of carbachol treatment. Cytokeratin 19 serves as a dependable marker for identifying ductal cells in salivary glands, except for granular convoluted tubules. Moreover, we have successfully developed an efficient method for isolating ductal cells from salivary glands.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"511-521"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106938","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}

引用次数: 0

Anti-inflammatory and glial response maintain normal colon function in trimethyltin-treated rats. 抗炎和神经胶质反应可维持三甲基锡处理过的大鼠的正常结肠功能。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-12-01 Epub Date: 2024-08-22 DOI: 10.1007/s00418-024-02320-x

Dian Eurike Septyaningtrias, Nur Salisa Siddik Muliyantoro, Yustina Andwi Ari Sumiwi, Rina Susilowati

{"title":"Anti-inflammatory and glial response maintain normal colon function in trimethyltin-treated rats.","authors":"Dian Eurike Septyaningtrias, Nur Salisa Siddik Muliyantoro, Yustina Andwi Ari Sumiwi, Rina Susilowati","doi":"10.1007/s00418-024-02320-x","DOIUrl":"10.1007/s00418-024-02320-x","url":null,"abstract":"Studies on the contribution of enteric neuropathy and intestinal homeostasis to central nervous system degeneration using animal models have reported varying results. Recently, colonic myenteric plexus degeneration was observed in trimethyltin-treated rats. Further characterization of this animal model is necessary to determine its potential for investigating the relationship between the enteric nervous system and central nervous system degeneration. In this study, trimethyltin-treated rats (8 mg/kg body weight, i.p.) were used to measure colonic function, structure, and possible colon abnormalities. The colonic function was assessed by measuring fecal pellet output and transit time. Hematoxylin and eosin staining and immunohistochemistry were performed to evaluate inflammatory profiles and intestinal epithelial cell homeostasis. The expression of mRNA encoding tight junction proteins was quantified with quantitative PCR to determine colon permeability. Histological examination of the colon revealed mucosal immune cell infiltration, crypt damage, and high iNOS and arginase-1 expression in the mucosal layer of trimethyltin-treated rats. At the same time, trimethyltin induced high expression of iNOS, arginase-1, and GFAP and increased cell death in the colonic myenteric plexus. The low cell proliferation and low goblet cell distribution suggested altered intestinal epithelial cell homeostasis in trimethyltin-treated rats. Trimethyltin also upregulated claudin 1 expression. However, normal colon function was preserved. In conclusion, the results show that trimethyltin induces colon inflammation and cell death in the colonic myenteric plexus, and disrupts intestinal epithelial cell homeostasis. However, the balance between anti-inflammatory and pro-inflammatory responses maintains normal colon function in trimethyltin-treated rats.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"477-486"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017294","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}

引用次数: 0

Mechanisms of S-phase arrest and mitochondrial dysfunction in complex III by DHODH inhibitors in tumorigenic TNBC cells. 致瘤 TNBC 细胞中 DHODH 抑制剂导致 S 期停滞和复合体 III 线粒体功能障碍的机制。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-11-18 DOI: 10.1007/s00418-024-02339-0

Muhammad Aiman Akmal Shahhiran, Mohamad Fairus Abdul Kadir, Nurshamimi Nor Rashid, Puteri Shafinaz Abdul-Rahman, Shatrah Othman

{"title":"Mechanisms of S-phase arrest and mitochondrial dysfunction in complex III by DHODH inhibitors in tumorigenic TNBC cells.","authors":"Muhammad Aiman Akmal Shahhiran, Mohamad Fairus Abdul Kadir, Nurshamimi Nor Rashid, Puteri Shafinaz Abdul-Rahman, Shatrah Othman","doi":"10.1007/s00418-024-02339-0","DOIUrl":"10.1007/s00418-024-02339-0","url":null,"abstract":"Dihydroorotate dehydrogenase (DHODH) inhibitors have recently gained increasing research interest owing to their potential for treating breast cancers. We explored their effects in different breast cancer subtypes, focusing on mitochondrial dysfunction. The sensitivity of different subtypes to the inhibitors was investigated with respect to DHODH expression, tumorigenic, and receptor status. Analysis of respiratory complexes, cell cycle, reactive oxygen species (ROS), and cell differentiation were performed. Four cell lines with different receptor status were included, namely MCF-7, MDAMB-231, SKBR-3, and MCF-10A. We showed that MCF-7 and MDAMB-231 cells of the subtypes (ER+/PR+/HER2-) and (ER-/PR-/HER2-), respectively, were responsive to brequinar. Brequinar (BQR) caused cell cycle arrest in the S-phase in sensitive subtypes of breast cells but induced cell differentiation only in poorly differentiated breast cells. All cell subtypes showed increased generation of ROS, both intracellular and mitochondrial ROS with a greater increase seen in mitochondrial ROS in response to DHODH inhibitor, subsequently contributing to mitochondrial dysfunction. BQR also disrupts the function of complex III in ER+/PR+ and triple negative breast cancer (TNBC) subtypes. Collectively, we have found that MDAMB-231 TNBC cell was the most affected by DHODH inhibition in terms of sensitivity, cell cycle arrest, induction of cell differentiation, production of ROS, and mitochondrial complexes disruption. In conclusion, these findings suggest that DHODH inhibitors can potentially become a valuable targeted therapy for TNBC subtype and further consolidates its therapeutic potential as part of the combinatorial therapy against this resilient breast cancer subtype.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"3"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667637","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}

引用次数: 0

Characterization of primary cilia in different epithelial cells of thyroid gland. 甲状腺不同上皮细胞中初级纤毛的特征。

IF 2.1 4区生物学

Histochemistry and Cell Biology Pub Date : 2024-11-18 DOI: 10.1007/s00418-024-02328-3

B Pérez-Fernández, V Vázquez-Román, J M Fernández-Santos, I Martín-Lacave

{"title":"Characterization of primary cilia in different epithelial cells of thyroid gland.","authors":"B Pérez-Fernández, V Vázquez-Román, J M Fernández-Santos, I Martín-Lacave","doi":"10.1007/s00418-024-02328-3","DOIUrl":"10.1007/s00418-024-02328-3","url":null,"abstract":"The primary cilium (PC) is a biosensor with diverse functions, depending on cellular type. In the thyroid, where it was first described, PCs are located at the apical pole of the follicular epithelium, sensing the lumen's environment. They probably contribute to follicular homeostasis, although their presence in other thyroid epithelial cells remains unclear. Thyroglobulin, stored in the lumen as colloid, is the primary regulator of thyroid-specific gene expression under constant TSH levels. The mechanism by which thyroglobulin signal is transduced remains unresolved. This study investigates the evolution of PCs in different types of thyroid follicles, based on their functional activity, using both normal human thyroids and functional thyroid pathologies as models. It also compares PC morphology between human and rat thyrocytes and explores their presence in other thyroid epithelial components such as C cells and ultimobranchial remnants. Human and Wistar rat thyroid tissues were analyzed using histological, immunohistochemical, immunofluorescence, and electron microscopy techniques. Morphometric analyses quantified PC changes (frequency and length) in various follicular patterns, and statistical analyses were performed. Four types of thyroid follicles were identified: active, hyperactive, hypoactive, and empty follicles. PCs were most abundant and longest in active and significantly reduced in empty follicles. PCs were more prominent in human than in rat thyrocytes, present in both normal and neoplastic C cells, but sporadic in ultimobranchial remnants. PCs vary according to follicular activity and likely act as mechanosensors in thyroid hormone regulation, detecting colloid density and contributing to the regulation of thyroid hormone biosynthesis.","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"4"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667471","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}

引用次数: 0