首页 > 最新文献

Pflugers Archiv : European journal of physiology最新文献

英文 中文
How do cells sense oxygen? 细胞如何感知氧气?
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1007/s00424-024-03000-4
Joachim Fandrey
{"title":"How do cells sense oxygen?","authors":"Joachim Fandrey","doi":"10.1007/s00424-024-03000-4","DOIUrl":"10.1007/s00424-024-03000-4","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1303-1305"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypoxia-inducible factors in postnatal mouse molar dental pulp development: insights into expression patterns, localisation and metabolic pathways. 出生后小鼠磨牙牙髓发育过程中的缺氧诱导因子:表达模式、定位和代谢途径的启示
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1007/s00424-024-03003-1
Kateřina Holomková, Barbora Veselá, Kateřina Dadáková, Paul T Sharpe, Hervé Lesot, Eva Matalová, Eva Švandová

Hypoxia is relevant to several physiological and pathological processes and this also applies for the tooth. The adaptive response to lowering oxygen concentration is mediated by hypoxia-inducible factors (HIFs). Since HIFs were shown to participate in the promotion of angiogenesis, stem cell survival, odontoblast differentiation and dentin formation, they may play a beneficial role in the tooth reparative processes. Although some data were generated in vitro, little is known about the in vivo context of HIFs in tooth development. In order to contribute to this field, the mouse mandibular first molar was used as a model.The expression and in situ localisation of HIFs were examined at postnatal (P) days P0, P7, P14, using RT-PCR and immunostaining. The expression pattern of a broad spectrum of hypoxia-related genes was monitored by customised PCR Arrays. Metabolic aspects were evaluated by determination of the lactate level and mRNA expression of the mitochondrial marker Nd1.The results show constant high mRNA expression of Hif1a, increasing expression of Hif2a, and very low expression of Hif3a during early postnatal molar development. In the examined period the localisation of HIFs in the nuclei of odontoblasts and the subodontoblastic layer identified their presence during odontoblastic differentiation. Additionally, the lower lactate level and higher expression of mitochondrial Nd1 in advanced development points to decreasing glycolysis during differentiation. Postnatal nuclear localisation of HIFs indicates a hypoxic state in specific areas of dental pulp as oxygen demands depend on physiological events such as crown and root dentin mineralization.

缺氧与多种生理和病理过程有关,这一点同样适用于牙齿。低氧诱导因子(HIFs)介导了对氧气浓度降低的适应性反应。由于低氧诱导因子被证明参与促进血管生成、干细胞存活、颌骨母细胞分化和牙本质形成,因此它们可能在牙齿修复过程中发挥有益作用。虽然一些数据是在体外产生的,但人们对 HIFs 在牙齿发育过程中的体内环境知之甚少。为了对这一领域有所贡献,我们以小鼠下颌第一臼齿为模型,使用 RT-PCR 和免疫染色法检测了 HIFs 在出生后(P)第 P0、P7 和 P14 天的表达和原位定位情况。定制的 PCR 阵列监测了多种缺氧相关基因的表达模式。结果显示,在出生后早期臼齿发育过程中,Hif1a 的 mRNA 表达量一直很高,Hif2a 的表达量不断增加,而 Hif3a 的表达量却很低。在研究期间,HIFs 在牙本质细胞核和牙本质下层的定位确定了它们在牙本质分化过程中的存在。此外,发育后期乳酸水平较低,线粒体 Nd1 表达较高,这表明在分化过程中糖酵解减少。出生后 HIFs 的核定位表明牙髓特定区域处于缺氧状态,因为氧需求取决于牙冠和牙根牙本质矿化等生理事件。
{"title":"Hypoxia-inducible factors in postnatal mouse molar dental pulp development: insights into expression patterns, localisation and metabolic pathways.","authors":"Kateřina Holomková, Barbora Veselá, Kateřina Dadáková, Paul T Sharpe, Hervé Lesot, Eva Matalová, Eva Švandová","doi":"10.1007/s00424-024-03003-1","DOIUrl":"10.1007/s00424-024-03003-1","url":null,"abstract":"<p><p>Hypoxia is relevant to several physiological and pathological processes and this also applies for the tooth. The adaptive response to lowering oxygen concentration is mediated by hypoxia-inducible factors (HIFs). Since HIFs were shown to participate in the promotion of angiogenesis, stem cell survival, odontoblast differentiation and dentin formation, they may play a beneficial role in the tooth reparative processes. Although some data were generated in vitro, little is known about the in vivo context of HIFs in tooth development. In order to contribute to this field, the mouse mandibular first molar was used as a model.The expression and in situ localisation of HIFs were examined at postnatal (P) days P0, P7, P14, using RT-PCR and immunostaining. The expression pattern of a broad spectrum of hypoxia-related genes was monitored by customised PCR Arrays. Metabolic aspects were evaluated by determination of the lactate level and mRNA expression of the mitochondrial marker Nd1.The results show constant high mRNA expression of Hif1a, increasing expression of Hif2a, and very low expression of Hif3a during early postnatal molar development. In the examined period the localisation of HIFs in the nuclei of odontoblasts and the subodontoblastic layer identified their presence during odontoblastic differentiation. Additionally, the lower lactate level and higher expression of mitochondrial Nd1 in advanced development points to decreasing glycolysis during differentiation. Postnatal nuclear localisation of HIFs indicates a hypoxic state in specific areas of dental pulp as oxygen demands depend on physiological events such as crown and root dentin mineralization.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1411-1421"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions. 活体 PHD1-3 氧传感器--从基因缺失中汲取的教训。
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-03-21 DOI: 10.1007/s00424-024-02944-x
Agnieszka E Jucht, Carsten C Scholz

Oxygen sensors enable cells to adapt to limited oxygen availability (hypoxia), affecting various cellular and tissue responses. Prolyl-4-hydroxylase domain 1-3 (PHD1-3; also called Egln1-3, HIF-P4H 1-3, HIF-PH 1-3) proteins belong to the Fe2+- and 2-oxoglutarate-dependent dioxygenase superfamily and utilise molecular oxygen (O2) alongside 2-oxoglutarate as co-substrate to hydroxylate two proline residues of α subunits of the dimeric hypoxia inducible factor (HIF) transcription factor. PHD1-3-mediated hydroxylation of HIF-α leads to its degradation and inactivation. Recently, various PHD inhibitors (PHI) have entered the clinics for treatment of renal anaemia. Pre-clinical analyses indicate that PHI treatment may also be beneficial in numerous other hypoxia-associated diseases. Nonetheless, the underlying molecular mechanisms of the observed protective effects of PHIs are only partly understood, currently hindering their translation into the clinics. Moreover, the PHI-mediated increase of Epo levels is not beneficial in all hypoxia-associated diseases and PHD-selective inhibition may be advantageous. Here, we summarise the current knowledge about the relevance and function of each of the three PHD isoforms in vivo, based on the deletion or RNA interference-mediated knockdown of each single corresponding gene in rodents. This information is crucial for our understanding of the physiological relevance and function of the PHDs as well as for elucidating their individual impact on hypoxia-associated diseases. Furthermore, this knowledge highlights which diseases may best be targeted by PHD isoform-selective inhibitors in case such pharmacologic substances become available.

氧传感器使细胞能够适应有限的氧气供应(缺氧),影响各种细胞和组织反应。脯氨酰-4-羟化酶结构域 1-3(PHD1-3,又称 Egln1-3、HIF-P4H 1-3、HIF-PH 1-3)蛋白属于铁-2+和 2-氧代戊二酸依赖性二氧酶超家族,利用分子氧(O2)和 2-氧代戊二酸作为辅助底物,羟化二聚体缺氧诱导因子(HIF)转录因子 α 亚基的两个脯氨酸残基。PHD1-3 介导的 HIF-α 羟基化导致其降解和失活。最近,各种 PHD 抑制剂(PHI)已进入临床,用于治疗肾性贫血。临床前分析表明,PHI 治疗对许多其他缺氧相关疾病也可能有益。然而,人们对 PHIs 保护作用的基本分子机制只有部分了解,这阻碍了 PHIs 在临床上的应用。此外,PHI 介导的 Epo 水平升高并非对所有缺氧相关疾病都有益处,PHD 选择性抑制可能更有优势。在此,我们根据啮齿类动物中每种单个相应基因的缺失或 RNA 干扰介导的基因敲除,总结了目前关于三种 PHD 异构体在体内的相关性和功能的知识。这些信息对于我们了解 PHD 的生理相关性和功能以及阐明它们各自对缺氧相关疾病的影响至关重要。此外,这些知识还突显了在 PHD 同工酶选择性抑制剂出现的情况下,哪些疾病可能是 PHD 同工酶选择性抑制剂的最佳靶点。
{"title":"PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.","authors":"Agnieszka E Jucht, Carsten C Scholz","doi":"10.1007/s00424-024-02944-x","DOIUrl":"10.1007/s00424-024-02944-x","url":null,"abstract":"<p><p>Oxygen sensors enable cells to adapt to limited oxygen availability (hypoxia), affecting various cellular and tissue responses. Prolyl-4-hydroxylase domain 1-3 (PHD1-3; also called Egln1-3, HIF-P4H 1-3, HIF-PH 1-3) proteins belong to the Fe<sup>2+</sup>- and 2-oxoglutarate-dependent dioxygenase superfamily and utilise molecular oxygen (O<sub>2</sub>) alongside 2-oxoglutarate as co-substrate to hydroxylate two proline residues of α subunits of the dimeric hypoxia inducible factor (HIF) transcription factor. PHD1-3-mediated hydroxylation of HIF-α leads to its degradation and inactivation. Recently, various PHD inhibitors (PHI) have entered the clinics for treatment of renal anaemia. Pre-clinical analyses indicate that PHI treatment may also be beneficial in numerous other hypoxia-associated diseases. Nonetheless, the underlying molecular mechanisms of the observed protective effects of PHIs are only partly understood, currently hindering their translation into the clinics. Moreover, the PHI-mediated increase of Epo levels is not beneficial in all hypoxia-associated diseases and PHD-selective inhibition may be advantageous. Here, we summarise the current knowledge about the relevance and function of each of the three PHD isoforms in vivo, based on the deletion or RNA interference-mediated knockdown of each single corresponding gene in rodents. This information is crucial for our understanding of the physiological relevance and function of the PHDs as well as for elucidating their individual impact on hypoxia-associated diseases. Furthermore, this knowledge highlights which diseases may best be targeted by PHD isoform-selective inhibitors in case such pharmacologic substances become available.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1307-1337"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decoding pathology: the role of computational pathology in research and diagnostics. 解码病理学:计算病理学在研究和诊断中的作用。
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-03 DOI: 10.1007/s00424-024-03002-2
David L Hölscher, Roman D Bülow

Traditional histopathology, characterized by manual quantifications and assessments, faces challenges such as low-throughput and inter-observer variability that hinder the introduction of precision medicine in pathology diagnostics and research. The advent of digital pathology allowed the introduction of computational pathology, a discipline that leverages computational methods, especially based on deep learning (DL) techniques, to analyze histopathology specimens. A growing body of research shows impressive performances of DL-based models in pathology for a multitude of tasks, such as mutation prediction, large-scale pathomics analyses, or prognosis prediction. New approaches integrate multimodal data sources and increasingly rely on multi-purpose foundation models. This review provides an introductory overview of advancements in computational pathology and discusses their implications for the future of histopathology in research and diagnostics.

传统的组织病理学以人工量化和评估为特点,面临着低通量和观察者之间的差异性等挑战,阻碍了病理诊断和研究中精准医学的引入。数字病理学的出现使得计算病理学得以引入,这是一门利用计算方法,尤其是基于深度学习(DL)技术的计算方法来分析组织病理学标本的学科。越来越多的研究表明,基于深度学习的病理模型在突变预测、大规模病理组学分析或预后预测等多项任务中表现出色。新方法整合了多模态数据源,并越来越依赖于多功能基础模型。这篇综述对计算病理学的进展进行了介绍性概述,并讨论了这些进展对未来组织病理学研究和诊断的影响。
{"title":"Decoding pathology: the role of computational pathology in research and diagnostics.","authors":"David L Hölscher, Roman D Bülow","doi":"10.1007/s00424-024-03002-2","DOIUrl":"https://doi.org/10.1007/s00424-024-03002-2","url":null,"abstract":"<p><p>Traditional histopathology, characterized by manual quantifications and assessments, faces challenges such as low-throughput and inter-observer variability that hinder the introduction of precision medicine in pathology diagnostics and research. The advent of digital pathology allowed the introduction of computational pathology, a discipline that leverages computational methods, especially based on deep learning (DL) techniques, to analyze histopathology specimens. A growing body of research shows impressive performances of DL-based models in pathology for a multitude of tasks, such as mutation prediction, large-scale pathomics analyses, or prognosis prediction. New approaches integrate multimodal data sources and increasingly rely on multi-purpose foundation models. This review provides an introductory overview of advancements in computational pathology and discusses their implications for the future of histopathology in research and diagnostics.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of caspase-8 cascade restrains the osteoclastogenic fate of bone marrow cells. 抑制 Caspase-8 级联可抑制骨髓细胞的破骨细胞生成命运。
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-04 DOI: 10.1007/s00424-024-02977-2
Barbora Veselá, Adéla Ševčíková, Kateřina Holomková, Alice Ramešová, Adéla Kratochvílova, Paul T Sharpe, Eva Matalová

Osteoclasts are multinucleated cells of hematopoietic origin, with a pivotal role in bone development and remodeling. Failure in osteoclast differentiation and activation leads to various bone disorders; thus, attention has focused on a search of molecules involved in osteoclast regulatory pathways. Caspase-8 appears to be an interesting candidate for further exploration, due to its potential function in bone development and homeostasis. Mouse bone marrow cells were differentiated into osteoclasts by RANKL stimulation. Increased activation of caspase-8 and its downstream executioner caspases (caspase-3 and caspase-6) was found during osteoclastogenesis. Subsequent inhibition of caspase-8, caspase-3, or caspase-6, respectively, during osteoclast differentiation showed distinct changes in the formation of TRAP-positive multinucleated cells and reduced expression of osteoclast markers including Acp5, Ctsk, Dcstamp, and Mmp9. Analysis of bone matrix resorption confirmed significantly reduced osteoclast function after caspase inhibition. The results clearly showed the role of caspases in the proper development of osteoclasts and contributed new knowledge about non-apoptotic function of caspases.

破骨细胞是来源于造血的多核细胞,在骨骼发育和重塑过程中发挥着关键作用。破骨细胞分化和激活失败会导致各种骨骼疾病;因此,人们把注意力集中在寻找参与破骨细胞调控途径的分子上。由于 Caspase-8 在骨骼发育和平衡中的潜在功能,它似乎是一个值得进一步探索的候选分子。小鼠骨髓细胞在 RANKL 刺激下分化为破骨细胞。在破骨细胞生成过程中发现,caspase-8 及其下游刽子手 caspases(caspase-3 和 caspase-6)的活化增加。随后在破骨细胞分化过程中分别抑制 caspase-8、caspase-3 或 caspase-6,结果显示 TRAP 阳性多核细胞的形成发生了明显变化,破骨细胞标志物(包括 Acp5、Ctsk、Dcstamp 和 Mmp9)的表达也有所减少。骨基质吸收分析证实,caspase抑制后破骨细胞功能明显降低。这些结果清楚地表明了caspase在破骨细胞正常发育过程中的作用,并为人们了解caspase的非凋亡功能提供了新的知识。
{"title":"Inhibition of caspase-8 cascade restrains the osteoclastogenic fate of bone marrow cells.","authors":"Barbora Veselá, Adéla Ševčíková, Kateřina Holomková, Alice Ramešová, Adéla Kratochvílova, Paul T Sharpe, Eva Matalová","doi":"10.1007/s00424-024-02977-2","DOIUrl":"10.1007/s00424-024-02977-2","url":null,"abstract":"<p><p>Osteoclasts are multinucleated cells of hematopoietic origin, with a pivotal role in bone development and remodeling. Failure in osteoclast differentiation and activation leads to various bone disorders; thus, attention has focused on a search of molecules involved in osteoclast regulatory pathways. Caspase-8 appears to be an interesting candidate for further exploration, due to its potential function in bone development and homeostasis. Mouse bone marrow cells were differentiated into osteoclasts by RANKL stimulation. Increased activation of caspase-8 and its downstream executioner caspases (caspase-3 and caspase-6) was found during osteoclastogenesis. Subsequent inhibition of caspase-8, caspase-3, or caspase-6, respectively, during osteoclast differentiation showed distinct changes in the formation of TRAP-positive multinucleated cells and reduced expression of osteoclast markers including Acp5, Ctsk, Dcstamp, and Mmp9. Analysis of bone matrix resorption confirmed significantly reduced osteoclast function after caspase inhibition. The results clearly showed the role of caspases in the proper development of osteoclasts and contributed new knowledge about non-apoptotic function of caspases.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1289-1302"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Basal release of 6-cyanodopamine from rat isolated vas deferens and its role on the tissue contractility. 大鼠离体输精管 6-氰基多巴胺的基础释放及其对组织收缩力的作用
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-04 DOI: 10.1007/s00424-024-02985-2
Caroline Fernanda Sanches Dal Pozzo, Jose Eduardo Maldonado Junior, José Britto-Júnior, João Felipe Agostini Badin, Valéria Barbosa de Souza, André Almeida Schenka, Larryn W Peterson, Adriano Fregonesi, Edson Antunes, Gilberto De Nucci

6-Cyanodopamine is a novel catecholamine released from rabbit isolated heart. However, it is not known whether this catecholamine presents any biological activity. Here, it was evaluated whether 6-cyanodopamine (6-CYD) is released from rat vas deferens and its effect on this tissue contractility. Basal release of 6-CYD, 6-nitrodopamine (6-ND), 6-bromodopamine, 6-nitrodopa, and 6-nitroadrenaline from vas deferens were quantified by LC-MS/MS. Electric-field stimulation (EFS) and concentration-response curves to noradrenaline, adrenaline, and dopamine of the rat isolated epididymal vas deferens (RIEVD) were performed in the absence and presence of 6-CYD and /or 6-ND. Expression of tyrosine hydroxylase was assessed by immunohistochemistry. The rat isolated vas deferens released significant amounts of both 6-CYD and 6-ND. The voltage-gated sodium channel blocker tetrodotoxin had no effect on the release of 6-CYD, but it virtually abolished 6-ND release. 6-CYD alone exhibited a negligible RIEVD contractile activity; however, at 10 nM, 6-CYD significantly potentiated the noradrenaline- and EFS-induced RIEVD contractions, whereas at 10 and 100 nM, it also significantly potentiated the adrenaline- and dopamine-induced contractions. The potentiation of noradrenaline- and adrenaline-induced contractions by 6-CYD was unaffected by tetrodotoxin. Co-incubation of 6-CYD (100 pM) with 6-ND (10 pM) caused a significant leftward shift and increased the maximal contractile responses to noradrenaline, even in the presence of tetrodotoxin. Immunohistochemistry revealed the presence of tyrosine hydroxylase in both epithelial cell cytoplasm of the mucosae and nerve fibers of RIEVD. The identification of epithelium-derived 6-CYD and its remarkable synergism with catecholamines indicate that epithelial cells may regulate vas deferens smooth muscle contractility.

6-氰基多巴胺是从兔离体心脏中释放出的一种新型儿茶酚胺。然而,这种儿茶酚胺是否具有生物活性尚不清楚。在此,研究人员对大鼠输精管是否释放 6-氰基多巴胺(6-CYD)及其对该组织收缩力的影响进行了评估。通过 LC-MS/MS,对输精管中 6-CYD、6-硝基多巴胺(6-ND)、6-溴多巴胺、6-硝基多巴和 6-硝基肾上腺素的基础释放量进行了量化。在 6-CYD 和/或 6-ND 不存在和存在的情况下,对大鼠离体附睾输精管(RIEVD)进行了电场刺激(EFS)并绘制了去甲肾上腺素、肾上腺素和多巴胺的浓度反应曲线。酪氨酸羟化酶的表达通过免疫组化进行评估。大鼠离体输精管释放了大量 6-CYD 和 6-ND。电压门控钠离子通道阻断剂河豚毒素对 6-CYD 的释放没有影响,但几乎消除了 6-ND 的释放。单独使用 6-CYD 时,其 RIEVD 收缩活性可忽略不计;但在 10 nM 时,6-CYD 可显著增强去甲肾上腺素和 EFS 诱导的 RIEVD 收缩,而在 10 nM 和 100 nM 时,它还可显著增强肾上腺素和多巴胺诱导的收缩。河豚毒素不会影响 6-CYD 对去甲肾上腺素和肾上腺素诱导的收缩的增效作用。将 6-CYD(100 pM)与 6-ND(10 pM)共孵育会引起明显的左移,并增加对去甲肾上腺素的最大收缩反应,即使在河豚毒素存在的情况下也是如此。免疫组化显示,RIEVD 的粘膜上皮细胞胞浆和神经纤维中都存在酪氨酸羟化酶。上皮源性 6-CYD 的鉴定及其与儿茶酚胺的显著协同作用表明,上皮细胞可能调节输精管平滑肌的收缩力。
{"title":"Basal release of 6-cyanodopamine from rat isolated vas deferens and its role on the tissue contractility.","authors":"Caroline Fernanda Sanches Dal Pozzo, Jose Eduardo Maldonado Junior, José Britto-Júnior, João Felipe Agostini Badin, Valéria Barbosa de Souza, André Almeida Schenka, Larryn W Peterson, Adriano Fregonesi, Edson Antunes, Gilberto De Nucci","doi":"10.1007/s00424-024-02985-2","DOIUrl":"10.1007/s00424-024-02985-2","url":null,"abstract":"<p><p>6-Cyanodopamine is a novel catecholamine released from rabbit isolated heart. However, it is not known whether this catecholamine presents any biological activity. Here, it was evaluated whether 6-cyanodopamine (6-CYD) is released from rat vas deferens and its effect on this tissue contractility. Basal release of 6-CYD, 6-nitrodopamine (6-ND), 6-bromodopamine, 6-nitrodopa, and 6-nitroadrenaline from vas deferens were quantified by LC-MS/MS. Electric-field stimulation (EFS) and concentration-response curves to noradrenaline, adrenaline, and dopamine of the rat isolated epididymal vas deferens (RIEVD) were performed in the absence and presence of 6-CYD and /or 6-ND. Expression of tyrosine hydroxylase was assessed by immunohistochemistry. The rat isolated vas deferens released significant amounts of both 6-CYD and 6-ND. The voltage-gated sodium channel blocker tetrodotoxin had no effect on the release of 6-CYD, but it virtually abolished 6-ND release. 6-CYD alone exhibited a negligible RIEVD contractile activity; however, at 10 nM, 6-CYD significantly potentiated the noradrenaline- and EFS-induced RIEVD contractions, whereas at 10 and 100 nM, it also significantly potentiated the adrenaline- and dopamine-induced contractions. The potentiation of noradrenaline- and adrenaline-induced contractions by 6-CYD was unaffected by tetrodotoxin. Co-incubation of 6-CYD (100 pM) with 6-ND (10 pM) caused a significant leftward shift and increased the maximal contractile responses to noradrenaline, even in the presence of tetrodotoxin. Immunohistochemistry revealed the presence of tyrosine hydroxylase in both epithelial cell cytoplasm of the mucosae and nerve fibers of RIEVD. The identification of epithelium-derived 6-CYD and its remarkable synergism with catecholamines indicate that epithelial cells may regulate vas deferens smooth muscle contractility.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1263-1277"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of autonomic heart rate modulations during childhood and adolescence. 儿童和青少年时期自律性心率调节的发展。
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-28 DOI: 10.1007/s00424-024-02979-0
Kateřina Helánová, Martina Šišáková, Katerina Hnatkova, Tomáš Novotný, Irena Andršová, Marek Malik

Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.

众所周知,成年人的心率受自主神经控制,但有关儿童和青少年心率控制发展的数据却很有限。研究人员记录了 1045 名 4 至 19 岁健康儿童和青少年(550 名女性)在重复 10 分钟仰卧、无支撑坐姿和无支撑站立姿势时的连续 12 导联心电图。在每种体位下都测量了心率,并评估了心率变异性指数(获得了 SDNN、RMSSD 以及高频(HF)和低频(LF)频率成分)。准归一化高频频率成分定义为 qnHF = HF/(HF + LF)。除其他外,这些测量值通过线性回归与年龄相关。仰卧位时,男女心率在每一年龄段的下降幅度都很大,但女性低于男性。在站立姿势下,每岁的心率下降幅度大大降低。在仰卧位时,RMSSD 和 qnHF 指数与年龄无关,但在坐位和站立位时,随着年龄的增长,RMSSD 和 qnHF 指数显著下降。相应地,LF/HF 比例在坐位和站立位时随着年龄的增长而急剧增加,但在仰卧位时则没有。该研究表明,在儿童和青少年时期,基线仰卧位副交感神经的影响几乎没有发展变化,但在幼儿时期,交感神经分支对迷走神经影响的反应较弱。虽然迷走神经对幼儿和年长儿童心脏期的调节作用相同,但对年幼儿童抑制交感神经影响的能力较弱。
{"title":"Development of autonomic heart rate modulations during childhood and adolescence.","authors":"Kateřina Helánová, Martina Šišáková, Katerina Hnatkova, Tomáš Novotný, Irena Andršová, Marek Malik","doi":"10.1007/s00424-024-02979-0","DOIUrl":"10.1007/s00424-024-02979-0","url":null,"abstract":"<p><p>Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1187-1207"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Explainable artificial intelligence for spectroscopy data: a review. 光谱数据的可解释人工智能:综述。
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-01 DOI: 10.1007/s00424-024-02997-y
Jhonatan Contreras, Thomas Bocklitz

Explainable artificial intelligence (XAI) has gained significant attention in various domains, including natural and medical image analysis. However, its application in spectroscopy remains relatively unexplored. This systematic review aims to fill this gap by providing a comprehensive overview of the current landscape of XAI in spectroscopy and identifying potential benefits and challenges associated with its implementation. Following the PRISMA guideline 2020, we conducted a systematic search across major journal databases, resulting in 259 initial search results. After removing duplicates and applying inclusion and exclusion criteria, 21 scientific studies were included in this review. Notably, most of the studies focused on using XAI methods for spectral data analysis, emphasizing identifying significant spectral bands rather than specific intensity peaks. Among the most utilized AI techniques were SHapley Additive exPlanations (SHAP), masking methods inspired by Local Interpretable Model-agnostic Explanations (LIME), and Class Activation Mapping (CAM). These methods were favored due to their model-agnostic nature and ease of use, enabling interpretable explanations without modifying the original models. Future research should propose new methods and explore the adaptation of other XAI employed in other domains to better suit the unique characteristics of spectroscopic data.

可解释人工智能(XAI)在自然和医学图像分析等多个领域都获得了极大关注。然而,其在光谱学中的应用仍相对欠缺。本系统综述旨在通过全面概述 XAI 在光谱学中的应用现状,并确定与实施 XAI 相关的潜在优势和挑战,从而填补这一空白。按照 2020 年 PRISMA 指南,我们在主要期刊数据库中进行了系统检索,得到了 259 项初步检索结果。在去除重复内容并应用纳入和排除标准后,21 项科学研究被纳入本综述。值得注意的是,大多数研究侧重于使用 XAI 方法进行光谱数据分析,强调识别重要的光谱带而不是特定的强度峰。其中使用最多的人工智能技术有 SHapley Additive exPlanations (SHAP)、受本地可解释模型解释 (LIME) 启发的掩蔽方法和类活化映射 (CAM)。这些方法因其与模型无关的性质和易用性而受到青睐,无需修改原始模型即可实现可解释性解释。未来的研究应提出新的方法,并探索如何调整其他领域采用的 XAI,以更好地适应光谱数据的独特性。
{"title":"Explainable artificial intelligence for spectroscopy data: a review.","authors":"Jhonatan Contreras, Thomas Bocklitz","doi":"10.1007/s00424-024-02997-y","DOIUrl":"https://doi.org/10.1007/s00424-024-02997-y","url":null,"abstract":"<p><p>Explainable artificial intelligence (XAI) has gained significant attention in various domains, including natural and medical image analysis. However, its application in spectroscopy remains relatively unexplored. This systematic review aims to fill this gap by providing a comprehensive overview of the current landscape of XAI in spectroscopy and identifying potential benefits and challenges associated with its implementation. Following the PRISMA guideline 2020, we conducted a systematic search across major journal databases, resulting in 259 initial search results. After removing duplicates and applying inclusion and exclusion criteria, 21 scientific studies were included in this review. Notably, most of the studies focused on using XAI methods for spectral data analysis, emphasizing identifying significant spectral bands rather than specific intensity peaks. Among the most utilized AI techniques were SHapley Additive exPlanations (SHAP), masking methods inspired by Local Interpretable Model-agnostic Explanations (LIME), and Class Activation Mapping (CAM). These methods were favored due to their model-agnostic nature and ease of use, enabling interpretable explanations without modifying the original models. Future research should propose new methods and explore the adaptation of other XAI employed in other domains to better suit the unique characteristics of spectroscopic data.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Strength and muscle mass development after a resistance-training period at terrestrial and normobaric intermittent hypoxia. 在陆地和常压间歇缺氧条件下进行阻力训练后的力量和肌肉质量发展。
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-25 DOI: 10.1007/s00424-024-02978-1
C Benavente, P Padial, B R Scott, F Almeida, G Olcina, S Pérez-Regalado, B Feriche

This study investigated the effect of a resistance training (RT) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO2 = 20.9%), HH (2,320 m asl) or NH (FiO2 = 15.9%). The participants completed an 8-week RT program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by RT in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca2+) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of RT under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.

本研究调查了在陆地(HH)和常压缺氧(NH)条件下进行阻力训练(RT)与在常压缺氧(N)条件下进行相同训练对肌肉肥大和最大力量发展的影响。33 名接受过力量训练的男性被分配到 N(FiO2 = 20.9%)、HH(海拔 2320 米)或 NH(FiO2 = 15.9%)。参加者完成了为期 8 周的全身运动 RT 计划(每周 3 次)。在训练计划前后,对下肢肌肉厚度和背蹲的 1RM 进行了评估。在训练计划第一节和最后一节前后,测量了压力、炎症(IL-6)和肌肉生长(活性 mTOR、肌促蛋白和 miRNA-206 的百分比)的血液指标。研究结果显示,所有组别都提高了 1RM 值,但在 NH 组中,RT 的提高幅度最大(p = 0.026)。由于 HH 和 N 中运动诱导的应激反应(乳酸和 Ca2+)中度到大量过剩,结果显示这两种条件下的肌肉厚度仅比 NH 增加(ES > 1.22)。与其他环境条件相比,在整个训练期间,只有在 HH 中发现活性 mTOR 的百分比有小幅到大幅增加,在 NH 中发现 IL-6、肌生长激素和 miR-206 的百分比有小幅到大幅增加。总之,结果并不支持在缺氧条件下 RT 比 N 对肌肉生长的预期额外益处,尽管它似乎有利于力量的增长。与 NH 相比,HH 实现了更大的肌肉增长,这证实了缺氧类型对结果的影响。
{"title":"Strength and muscle mass development after a resistance-training period at terrestrial and normobaric intermittent hypoxia.","authors":"C Benavente, P Padial, B R Scott, F Almeida, G Olcina, S Pérez-Regalado, B Feriche","doi":"10.1007/s00424-024-02978-1","DOIUrl":"10.1007/s00424-024-02978-1","url":null,"abstract":"<p><p>This study investigated the effect of a resistance training (R<sub>T</sub>) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO<sub>2</sub> = 20.9%), HH (2,320 m asl) or NH (FiO<sub>2</sub> = 15.9%). The participants completed an 8-week R<sub>T</sub> program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by R<sub>T</sub> in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca<sup>2+</sup>) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of R<sub>T</sub> under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1221-1233"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A role for sirtuin 1 in FGF23 activation following β-glycerophosphate treatment. β-甘油磷酸酯处理后,sirtuin 1 在 FGF23 激活过程中发挥作用。
IF 2.9 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-21 DOI: 10.1007/s00424-024-02974-5
Danielle M A Ratsma, Max Muller, Marijke Koedam, M Carola Zillikens, Bram C J van der Eerden

Phosphate homeostasis is vital for many biological processes and disruptions in circulating levels can be detrimental. While the mechanisms behind FGF23 regulation have been regularly studied, the role of extracellular phosphate sensing and its impact on fibroblast growth factor 23 (FGF23) expression remains unclear. This study aimed to investigate the involvement of reactive oxygen species (ROS), silent information regulator 1 (SIRT1), and Hairy and Enhancer of Split-1 (HES1) in regulating FGF23 in FGF23 expressing MC3T3-E1 cells. MC3T3-E1 cells treated with β-glycerophosphate (BGP) resulted in increased Fgf23 expression. Inhibition of ROS formation by inhibition of NADPH oxidase, which is essential for ROS production, did not affect this response to BGP, suggesting ROS is not involved in this process. Moreover, treatment with tert-butyl hydroperoxide (TBHP), a ROS-inducing agent, did not increase Fgf23 expression. This suggests that ROS machinery is not involved in FGF23 stimulation as previously suggested. Nonetheless, inhibition of SIRT1 using Ex527 eliminated the Fgf23 response to BGP, indicating its involvement in FGF23 regulation after BGP treatment. Indeed, activation of SIRT1 using SRT1720 increased Fgf23 expression. Moreover, transcription factor Hes1 was upregulated by BGP treatment, which was diminished when cells were treated with Ex527 implying it is also regulated through SIRT1. These findings suggest the existence of an upstream SIRT1-HES1 axis in the regulation of FGF23 by phosphate, though we were unable to find a role for ROS in this process. Further research should provide insights into phosphate homeostasis and potential therapeutic targets for phosphate-related disorders.

磷酸盐平衡对许多生物过程都至关重要,循环水平的紊乱可能会造成危害。虽然人们经常研究 FGF23 的调控机制,但细胞外磷酸盐感应的作用及其对成纤维细胞生长因子 23(FGF23)表达的影响仍不清楚。本研究旨在探讨活性氧(ROS)、沉默信息调节因子1(SIRT1)和毛发与分裂增强因子1(HES1)参与调控表达FGF23的MC3T3-E1细胞中的FGF23。用β-甘油磷酸酯(BGP)处理MC3T3-E1细胞可增加Fgf23的表达。通过抑制产生 ROS 所必需的 NADPH 氧化酶来抑制 ROS 的形成,并不会影响细胞对 BGP 的反应,这表明 ROS 并未参与这一过程。此外,用 ROS 诱导剂叔丁基过氧化氢(TBHP)处理也不会增加 Fgf23 的表达。这表明,ROS 机制并不像之前所说的那样参与了 FGF23 的刺激。然而,使用 Ex527 抑制 SIRT1 可消除 Fgf23 对 BGP 的反应,这表明它参与了 BGP 处理后的 FGF23 调节。事实上,使用 SRT1720 激活 SIRT1 会增加 Fgf23 的表达。此外,转录因子 Hes1 在 BGP 处理后上调,而用 Ex527 处理细胞后上调幅度减小,这意味着它也通过 SIRT1 调节。这些发现表明,在磷酸盐对 FGF23 的调控过程中,存在一个上游 SIRT1-HES1 轴,尽管我们未能发现 ROS 在这一过程中的作用。进一步的研究将为磷酸盐平衡和磷酸盐相关疾病的潜在治疗靶点提供深入的见解。
{"title":"A role for sirtuin 1 in FGF23 activation following β-glycerophosphate treatment.","authors":"Danielle M A Ratsma, Max Muller, Marijke Koedam, M Carola Zillikens, Bram C J van der Eerden","doi":"10.1007/s00424-024-02974-5","DOIUrl":"10.1007/s00424-024-02974-5","url":null,"abstract":"<p><p>Phosphate homeostasis is vital for many biological processes and disruptions in circulating levels can be detrimental. While the mechanisms behind FGF23 regulation have been regularly studied, the role of extracellular phosphate sensing and its impact on fibroblast growth factor 23 (FGF23) expression remains unclear. This study aimed to investigate the involvement of reactive oxygen species (ROS), silent information regulator 1 (SIRT1), and Hairy and Enhancer of Split-1 (HES1) in regulating FGF23 in FGF23 expressing MC3T3-E1 cells. MC3T3-E1 cells treated with β-glycerophosphate (BGP) resulted in increased Fgf23 expression. Inhibition of ROS formation by inhibition of NADPH oxidase, which is essential for ROS production, did not affect this response to BGP, suggesting ROS is not involved in this process. Moreover, treatment with tert-butyl hydroperoxide (TBHP), a ROS-inducing agent, did not increase Fgf23 expression. This suggests that ROS machinery is not involved in FGF23 stimulation as previously suggested. Nonetheless, inhibition of SIRT1 using Ex527 eliminated the Fgf23 response to BGP, indicating its involvement in FGF23 regulation after BGP treatment. Indeed, activation of SIRT1 using SRT1720 increased Fgf23 expression. Moreover, transcription factor Hes1 was upregulated by BGP treatment, which was diminished when cells were treated with Ex527 implying it is also regulated through SIRT1. These findings suggest the existence of an upstream SIRT1-HES1 axis in the regulation of FGF23 by phosphate, though we were unable to find a role for ROS in this process. Further research should provide insights into phosphate homeostasis and potential therapeutic targets for phosphate-related disorders.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1279-1288"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Pflugers Archiv : European journal of physiology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1