Lung neuroendocrine neoplasms (NENs) are a diverse group of tumors characterized by neuroendocrine (NE) differentiation. Among lung NENs, lung carcinoid (LC) is a rare tumor with unique characteristics. Recent research has highlighted the importance of transcription factors (TFs) in establishing gene expression programs in lung NENs such as small cell lung carcinoma. However, the TFs that control the gene expression of LC are largely unknown. In this study, we report the expression and potential function of a TF called Prospero homeobox protein1 (PROX1) in LC. Publicly available transcriptome data suggested that PROX1 was highly expressed in LC tissues, which was confirmed by immunohistochemical analysis on a tissue microarray. Knockdown of PROX1 did not impact the cellular viability of an LC-derived cell line, NCI-H727. Meanwhile, transcriptome analysis revealed that PROX1 knockdown altered the expression of genes involved in NE differentiation. ASCL1, CHGA, CALCA, and LINC00261 were suggested as downstream genes of PROX1. These findings indicate that PROX1 may play an important role in the NE identity of LC by regulating the expression of key target genes.
{"title":"PROX1 is a regulator of neuroendocrine-related gene expression in lung carcinoid","authors":"Kouhei Sakurai, Tatsuya Ando, Yasuhiro Sakai, Yuichiro Mori, Satoru Nakamura, Taku Kato, Hiroyasu Ito","doi":"10.1007/s13577-024-01109-3","DOIUrl":"https://doi.org/10.1007/s13577-024-01109-3","url":null,"abstract":"<p>Lung neuroendocrine neoplasms (NENs) are a diverse group of tumors characterized by neuroendocrine (NE) differentiation. Among lung NENs, lung carcinoid (LC) is a rare tumor with unique characteristics. Recent research has highlighted the importance of transcription factors (TFs) in establishing gene expression programs in lung NENs such as small cell lung carcinoma. However, the TFs that control the gene expression of LC are largely unknown. In this study, we report the expression and potential function of a TF called Prospero homeobox protein1 (PROX1) in LC. Publicly available transcriptome data suggested that <i>PROX1</i> was highly expressed in LC tissues, which was confirmed by immunohistochemical analysis on a tissue microarray. Knockdown of <i>PROX1</i> did not impact the cellular viability of an LC-derived cell line, NCI-H727. Meanwhile, transcriptome analysis revealed that <i>PROX1</i> knockdown altered the expression of genes involved in NE differentiation. <i>ASCL1</i>, <i>CHGA</i>, <i>CALCA</i>, and <i>LINC00261</i> were suggested as downstream genes of PROX1. These findings indicate that PROX1 may play an important role in the NE identity of LC by regulating the expression of key target genes.</p>","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":"113 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.1007/s13577-024-01062-1
Liping Guo, Ke Li, Yan Ma, Huaimin Niu, Jun Li, Xin-hua Shao, Na Li, Yuehui Sun, Haixiong Wang
{"title":"MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction.","authors":"Liping Guo, Ke Li, Yan Ma, Huaimin Niu, Jun Li, Xin-hua Shao, Na Li, Yuehui Sun, Haixiong Wang","doi":"10.1007/s13577-024-01062-1","DOIUrl":"https://doi.org/10.1007/s13577-024-01062-1","url":null,"abstract":"","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":"36 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic diversity among the present Japanese population: evidence from genotyping of human cell lines established in Japan.","authors":"Fumio Kasai, Makoto Fukushima, Yohei Miyagi, Yukio Nakamura","doi":"10.1007/s13577-024-01055-0","DOIUrl":"https://doi.org/10.1007/s13577-024-01055-0","url":null,"abstract":"","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":" 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140685538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.1007/s13577-024-01060-3
Miki Iwai, Etsuko Yokota, Yuta Ishida, T. Yukawa, Yoshio Naomoto, Y. Monobe, M. Haisa, N. Takigawa, T. Fukazawa, T. Yamatsuji
{"title":"Establishment and characterization of novel high mucus-producing lung tumoroids derived from a patient with pulmonary solid adenocarcinoma.","authors":"Miki Iwai, Etsuko Yokota, Yuta Ishida, T. Yukawa, Yoshio Naomoto, Y. Monobe, M. Haisa, N. Takigawa, T. Fukazawa, T. Yamatsuji","doi":"10.1007/s13577-024-01060-3","DOIUrl":"https://doi.org/10.1007/s13577-024-01060-3","url":null,"abstract":"","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":" 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140692756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.1007/s13577-024-01061-2
Kohei Mizuno, Osamu Okitsu, Mako Goto, Atsuko Kusuhara, Koji Kusuhara
{"title":"Polyvinylpyrrolidone can prevent oolemma lysis caused by abnormal rupture of the plasma membrane in Piezo-ICSI.","authors":"Kohei Mizuno, Osamu Okitsu, Mako Goto, Atsuko Kusuhara, Koji Kusuhara","doi":"10.1007/s13577-024-01061-2","DOIUrl":"https://doi.org/10.1007/s13577-024-01061-2","url":null,"abstract":"","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":"10 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140705374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.1007/s13577-024-01059-w
Zhenfeng Ye, Jing Zhang, Zhou Xu, Zhangwang Li, Gaomin Huang, Bin Tong, Panpan Xia, Yunfeng Shen, Honglin Hu, Peng Yu, Xiaoqing Xi
Acute kidney injury (AKI) induced by renal ischemia/reperfusion injury (IRI) is a severe clinical condition. ROS accumulation, antioxidant pathways deficiency, and inflammation are involved in IRI. Pioglitazone (Pio) exerts anti-inflammatory and antioxidant effects. The aim of this study was to explore the protective effects of pioglitazone against IRI-induced AKI. Pathogen-free Sprague–Dawley (SD) rats were arbitrarily divided into four groups: Sham operation group Control (CON) group, CON + Pio group, I/R + Saline group, and I/R + Pio group. In addition, HK-2 cells were subjected to hypoxia and reoxygenation to develop an H/R model for investigation of the protective mechanism of Pio. Pretreatment with pioglitazone in the model rats reduced urea nitrogen and creatinine levels, histopathological scores, and cytotoxicity after IRI. Pioglitazone treatment significantly attenuated renal cell apoptosis, decreased cytotoxicity, increased Bcl-2 expression, and downregulated Bax expression. Besides, the levels of ROS and inflammatory factors, including NLRP3, ASC, pro-IL-1β, pro-caspase-1, cleaved-caspase-1, TNF-α, IL-6, and IL-1β, in I/R rats and H/R cells were normalized by the pioglitazone treatment. Pioglitazone improved IRI-induced AKI by attenuating oxidative stress and NLRP3 inflammasome activation. Therefore, pioglitazone has the potential to serve as a novel agent for renal IRI treatment and prevention.
肾缺血再灌注损伤(IRI)诱发的急性肾损伤(AKI)是一种严重的临床症状。ROS 积累、抗氧化途径缺乏和炎症都与 IRI 有关。吡格列酮具有抗炎和抗氧化作用。本研究旨在探讨吡格列酮对IRI诱导的AKI的保护作用。将无病原体的 Sprague-Dawley (SD) 大鼠任意分为四组:假手术组 对照组(CON)、CON + Pio 组、I/R + 盐水组和 I/R + Pio 组。此外,还对 HK-2 细胞进行缺氧和再氧,以建立 H/R 模型,研究 Pio 的保护机制。对模型大鼠进行吡格列酮预处理可降低IRI后的尿素氮和肌酐水平、组织病理学评分和细胞毒性。吡格列酮治疗可明显减轻肾细胞凋亡,降低细胞毒性,增加 Bcl-2 的表达,下调 Bax 的表达。此外,吡格列酮治疗后,I/R大鼠和H/R细胞中的ROS和炎症因子,包括NLRP3、ASC、pro-IL-1β、pro-caspase-1、cleaved-caspase-1、TNF-α、IL-6和IL-1β的水平均恢复正常。吡格列酮通过减轻氧化应激和NLRP3炎性体的激活改善了IRI诱导的AKI。因此,吡格列酮有望成为治疗和预防肾脏IRI的新型药物。
{"title":"Pioglitazone ameliorates ischemia/reperfusion-induced acute kidney injury via oxidative stress attenuation and NLRP3 inflammasome","authors":"Zhenfeng Ye, Jing Zhang, Zhou Xu, Zhangwang Li, Gaomin Huang, Bin Tong, Panpan Xia, Yunfeng Shen, Honglin Hu, Peng Yu, Xiaoqing Xi","doi":"10.1007/s13577-024-01059-w","DOIUrl":"https://doi.org/10.1007/s13577-024-01059-w","url":null,"abstract":"<p>Acute kidney injury (AKI) induced by renal ischemia/reperfusion injury (IRI) is a severe clinical condition. ROS accumulation, antioxidant pathways deficiency, and inflammation are involved in IRI. Pioglitazone (Pio) exerts anti-inflammatory and antioxidant effects. The aim of this study was to explore the protective effects of pioglitazone against IRI-induced AKI. Pathogen-free Sprague–Dawley (SD) rats were arbitrarily divided into four groups: Sham operation group Control (CON) group, CON + Pio group, I/R + Saline group, and I/R + Pio group. In addition, HK-2 cells were subjected to hypoxia and reoxygenation to develop an H/R model for investigation of the protective mechanism of Pio. Pretreatment with pioglitazone in the model rats reduced urea nitrogen and creatinine levels, histopathological scores, and cytotoxicity after IRI. Pioglitazone treatment significantly attenuated renal cell apoptosis, decreased cytotoxicity, increased Bcl-2 expression, and downregulated Bax expression. Besides, the levels of ROS and inflammatory factors, including NLRP3, ASC, pro-IL-1β, pro-caspase-1, cleaved-caspase-1, TNF-α, IL-6, and IL-1β, in I/R rats and H/R cells were normalized by the pioglitazone treatment. Pioglitazone improved IRI-induced AKI by attenuating oxidative stress and NLRP3 inflammasome activation. Therefore, pioglitazone has the potential to serve as a novel agent for renal IRI treatment and prevention.</p>","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":"39 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1007/s13577-024-01057-y
Junxiong Zhang, Zhongxin Tian, Chao Qin, Mohammad Reza Momeni
Physical activity on a regular basis has been shown to bolster the overall wellness of an individual; research is now revealing that these changes are accompanied by epigenetic modifications. Regular exercise has been proven to make intervention plans more successful and prolong adherence to them. When it comes to epigenetic changes, there are four primary components. This includes changes to the DNA, histones, expression of particular non-coding RNAs and DNA methylation. External triggers, such as physical activity, can lead to modifications in the epigenetic components, resulting in changes in the transcription process. This report pays attention to the current knowledge that pertains to the epigenetic alterations that occur after exercise, the genes affected and the resulting characteristics.
事实证明,经常进行体育锻炼可以促进个人的整体健康;现在的研究显示,这些变化伴随着表观遗传学的改变。事实证明,定期锻炼能使干预计划更加成功,并延长计划的坚持时间。说到表观遗传学的变化,主要有四个组成部分。这包括 DNA、组蛋白、特定非编码 RNA 的表达和 DNA 甲基化的变化。体力活动等外部触发因素可导致表观遗传成分的改变,从而引起转录过程的变化。本报告关注与运动后发生的表观遗传改变、受影响的基因以及由此产生的特征有关的现有知识。
{"title":"The effects of exercise on epigenetic modifications: focus on DNA methylation, histone modifications and non-coding RNAs","authors":"Junxiong Zhang, Zhongxin Tian, Chao Qin, Mohammad Reza Momeni","doi":"10.1007/s13577-024-01057-y","DOIUrl":"https://doi.org/10.1007/s13577-024-01057-y","url":null,"abstract":"<p>Physical activity on a regular basis has been shown to bolster the overall wellness of an individual; research is now revealing that these changes are accompanied by epigenetic modifications. Regular exercise has been proven to make intervention plans more successful and prolong adherence to them. When it comes to epigenetic changes, there are four primary components. This includes changes to the DNA, histones, expression of particular non-coding RNAs and DNA methylation. External triggers, such as physical activity, can lead to modifications in the epigenetic components, resulting in changes in the transcription process. This report pays attention to the current knowledge that pertains to the epigenetic alterations that occur after exercise, the genes affected and the resulting characteristics.</p>","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":"113 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient’s tumour tissue. Notably, MTC-22 cells, and the patient’s carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations—one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase—were seen in the patient’s tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.
{"title":"Establishment of a human ovarian clear cell carcinoma cell line mutant in PIK3CB but not PIK3CA","authors":"Hitomi Hoshino, Daisuke Inoue, Akiko Shinagawa, Hisato Yoshida, Shohei Shigeto, Kazuyuki Matsuda, Tomoya O. Akama, Yoshio Yoshida, Motohiro Kobayashi","doi":"10.1007/s13577-024-01058-x","DOIUrl":"https://doi.org/10.1007/s13577-024-01058-x","url":null,"abstract":"<p>A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient’s tumour tissue. Notably, MTC-22 cells, and the patient’s carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations—one in <i>ARID1A</i>, which encodes the AT-rich interaction domain containing protein 1A, and the other in <i>PIK3CB,</i> which encodes the catalytic subunit of phosphoinositide 3-kinase—were seen in the patient’s tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring <i>PIK3CB</i> mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.</p>","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}