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The role of mesenchymal stem cells and their exosomes in radiotherapy: A new opportunity or a potential threat 间充质干细胞及其外泌体在放射治疗中的作用:一个新的机会或潜在的威胁
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-26 DOI: 10.1016/j.bbagen.2025.130823
Fatemeh Zeinalzadeh , Seyedeh Nasibeh Mousavikia , Mohammad Taghi Bahreyni Toossi , Hosein Azimian
Cancer remains a major global health problem characterized by complex biological mechanisms and diverse clinical manifestations. Radiotherapy is a key element in cancer treatment. However, radioresistance is a major obstacle to achieving optimal results. This resistance is associated with several factors, including genetic and epigenetic changes in tumor cells that allow cancer cells to survive and proliferate despite radiation exposure. In this context, mesenchymal stem cells (MSCs) play an important role in the tumor microenvironment. Due to their unique properties such as self-renewal, migration to tumors via the bloodstream and involvement in paracrine signaling, they are important for understanding cancer biology and treatment responses. MSCs can release exosomes that can promote intercellular communication and influence tumor response to radiotherapy. However, the role of MSCs in cancer is complex and sometimes contradictory. In some contexts they may exhibit tumor suppressive effects, while in others they promote tumor growth and metastasis. This duality raises important questions about their overall impact on cancer therapy, particularly in relation to radiotherapy. This review will first explore the multifaceted role of MSCs and their exosomes as key mediators of cellular communication within the tumor microenvironment, and then assess the implications of these interactions for radiotherapy, focusing on how MSCs may influence treatment efficacy and the potential to harness their properties to improve therapeutic outcomes.
癌症仍然是一个主要的全球健康问题,其特点是生物学机制复杂,临床表现多样。放射治疗是癌症治疗的一个关键因素。然而,辐射阻力是实现最佳结果的主要障碍。这种抗性与几个因素有关,包括肿瘤细胞的遗传和表观遗传变化,这些变化使癌细胞能够在辐射照射下存活和增殖。在这种情况下,间充质干细胞(MSCs)在肿瘤微环境中发挥着重要作用。由于其独特的特性,如自我更新,通过血液迁移到肿瘤和参与旁分泌信号,它们对了解癌症生物学和治疗反应非常重要。MSCs可以释放外泌体,促进细胞间通讯并影响肿瘤对放疗的反应。然而,间充质干细胞在癌症中的作用是复杂的,有时是矛盾的。在某些情况下,它们可能表现出肿瘤抑制作用,而在其他情况下,它们促进肿瘤生长和转移。这种双重性提出了关于它们对癌症治疗的总体影响的重要问题,特别是与放射治疗有关的问题。本综述将首先探讨间质干细胞及其外泌体作为肿瘤微环境中细胞通讯的关键介质的多方面作用,然后评估这些相互作用对放射治疗的影响,重点关注间质干细胞如何影响治疗效果以及利用其特性改善治疗结果的潜力。
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引用次数: 0
N-glycosylation of CD4+ T cell changes with the development in Graves' disease and is sensitive to methimazole treatment CD4+ T细胞n -糖基化随graves病的发展而变化,对甲巯咪唑治疗敏感。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-25 DOI: 10.1016/j.bbagen.2025.130824
Sara Trzos , Marta Szewczyk , Paweł Link-Lenczowski , Grzegorz Sokołowski , Małgorzata Trofimiuk-Müldner , Katarzyna Bocian , Ewa Pocheć
Graves' disease (GD) is one of the most common autoimmune disorders. Helper T (Th) cells, whose surface receptors are rich in glycans, are involved in the GD pathomechanism. N-glycosylation is altered during autoimmunity and can be modulated by pharmacotherapy. We hypothesized that changes in Th glycosylation accompany GD, and the glycome of these cells is sensitive to methimazole therapy. The study group consisted of patients with Graves' disease before (GD) and after (GD/T) restoring euthyroidism as a result of methimazole therapy. In the control group, healthy donors were recruited. Th cells were isolated from PBMCs and sorted into a subpopulation of CD4+CD25 cells and those expressing the CD25 late activation marker (CD4+CD25+). MALDI-Tof MS was used for analysis of N-linked glycans, and the expression of glycosyltransferases was determined by RT-qPCR. The N-glycosylation profile of CD4+ cell subpopulations differed in the ratio of the complex-to-oligomannose N-glycans in GD. Complex N-glycans are partially replaced by oligomannose forms, and their structure is shortened by agalactosylation in CD4+CD25 cells from GD. The rearrangement of N-glycans in CD4+CD25+ cells has the opposite direction, namely the ratio is shifted towards complex structures in GD. The changes in the N-glycan profile were reflected partly in MGAT5 and FUT8 expression. Methimazole to some extent normalized the glycosyltransferase levels and affected the N-linked glycans profile. Our study shows N-glycosylation changes in CD4+ T cells in GD development and methimazole therapy for the first time. Further studies are needed to determine the functional aspect of the identified glycosylation changes in thyroid autoimmunity.
格雷夫斯病(GD)是最常见的自身免疫性疾病之一。辅助性T (Th)细胞,其表面受体富含聚糖,参与GD的病理机制。n -糖基化在自身免疫过程中发生改变,可通过药物治疗进行调节。我们假设GD伴有Th糖基化的变化,这些细胞的糖基化对甲巯咪唑治疗敏感。研究组为经甲巯咪唑治疗恢复甲亢前(GD/T)和后(GD/T) Graves病患者。在对照组中,招募健康的供体。这些细胞从pbmc中分离出来,并分为CD4+CD25-细胞亚群和表达CD25晚期激活标志物(CD4+CD25+)的细胞亚群。采用MALDI-Tof质谱法分析n链聚糖,RT-qPCR法检测糖基转移酶的表达。CD4+细胞亚群的n -糖基化谱在GD中复合物与寡甘露糖n -聚糖的比例不同。在GD的CD4+CD25-细胞中,n -甘聚糖复合物部分被寡甘露糖形式所取代,其结构因无半乳糖化而缩短。CD4+CD25+细胞中n -聚糖的重排方向相反,即在GD中比例向复杂结构转移。n -聚糖谱的变化部分反映在MGAT5和FUT8的表达上。甲巯咪唑在一定程度上使糖基转移酶水平正常化,并影响n链聚糖谱。我们的研究首次揭示了GD发展和甲巯咪唑治疗中CD4+ T细胞n -糖基化的变化。需要进一步的研究来确定甲状腺自身免疫中糖基化变化的功能方面。
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引用次数: 0
Dual generation of stereo- and linear-specific monoclonal antibodies through B-cell receptors by DNA and cell immunization for therapeutic applications 双代立体和线性特异性单克隆抗体通过b细胞受体通过DNA和细胞免疫治疗应用。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-22 DOI: 10.1016/j.bbagen.2025.130822
Chiho Miyamae , Yushi Isozaki , Kanta Tsumoto , Masahiro Tomita
The optimized stereospecific targeting (SST) technique features selective generation of conformation-specific monoclonal antibodies against membranous proteins with high specificity after DNA and cell immunization. This technology consists of two critical steps, which are specific selection of sensitized B lymphocytes by antigen-expressing myeloma cells through B-cell receptors (BCRs) and selective fusion of B cell-myeloma cell complexes by electrical pulses to produce hybridoma cells secreting stereospecific monoclonal antibodies. Here we were able to verify the critical step for the selection of B lymphocytes by intact antigen-expressing myeloma cells by a double-label immunofluorescence analysis. Interestingly, the cell complex was a single attachment. Furthermore, we newly found the new progress that the optimized SST technique offered dual production of anti-intact and anti-linear specific monoclonal antibodies against a human ephrin type-A receptor 2 (hEphA2). The optimized SST technique may be useful for producing not only stereospecific monoclonal antibodies, but also primary-specific monoclonal antibodies based on the selection of sensitized B lymphocytes by the target intact antigen through BCRs. It would elicit more advanced medical applications by generating dual monoclonal antibodies against the intact antigen.
优化后的立体特异性靶向(SST)技术在DNA和细胞免疫后选择性地产生针对膜蛋白的构象特异性单克隆抗体,具有高特异性。该技术包括两个关键步骤,即抗原表达的骨髓瘤细胞通过B细胞受体(bcr)特异性选择致敏的B淋巴细胞,以及通过电脉冲选择性融合B细胞-骨髓瘤细胞复合物以产生分泌立体特异性单克隆抗体的杂交瘤细胞。在这里,我们能够通过双标记免疫荧光分析验证完整抗原表达骨髓瘤细胞选择B淋巴细胞的关键步骤。有趣的是,细胞复合体是一个单独的附着体。此外,我们还发现了新的进展,即优化后的SST技术可以双重生产抗完整型和抗线性型特异性单克隆抗体,用于抗人ephrin - a型受体2 (hEphA2)。优化后的SST技术不仅可用于生产立体特异性单克隆抗体,还可用于生产基于靶完整抗原通过bcr选择致敏B淋巴细胞的初级特异性单克隆抗体。通过产生针对完整抗原的双单克隆抗体,将引发更先进的医学应用。
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引用次数: 0
Mastering the plant growth symphony: The interplay between calcium sensing machinery and phytohormone signaling during abiotic stress 掌握植物生长交响曲:在非生物胁迫下钙感知机制和植物激素信号之间的相互作用。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-17 DOI: 10.1016/j.bbagen.2025.130820
Tanashvi Seth, Shruti Saxena, Barkha Ravi, Girdhar K. Pandey
Climate change introduces a multitude of abiotic stressors, affecting plants' ability to thrive and produce. Abiotic stresses significantly impair plant growth, development, and production, jeopardizing food security. Despite extensive research on individual stress adaptation mechanisms, a critical gap remains in understanding the synergistic role of calcium (Ca2+) signaling and phytohormonal regulation in plant stress responses. Ca2+, a ubiquitous second messenger, plays a pivotal role in stress perception and signal transduction, while phytohormones regulate adaptive physiological and molecular responses. This review aims to bridge the knowledge gap by synthesizing recent advancements in Ca2+-phytohormone interactions and their combined role in enhancing plant resilience to abiotic stress. Hence, understanding these interconnected signaling cascades would pave the path for the development of innovative strategies for enhancing crop stress tolerance, thereby promoting sustainable agriculture in the face of climate change.
气候变化引入了大量的非生物压力源,影响了植物的生长和生产能力。非生物胁迫严重损害植物生长、发育和生产,危及粮食安全。尽管对个体胁迫适应机制进行了广泛的研究,但在了解钙(Ca2+)信号和植物激素调节在植物胁迫反应中的协同作用方面仍存在关键空白。Ca2+是一种普遍存在的第二信使,在胁迫感知和信号转导中起关键作用,而植物激素调节适应性生理和分子反应。本文旨在通过综合Ca2+-植物激素相互作用及其在增强植物抗非生物胁迫中的综合作用的最新进展来弥合这方面的知识差距。因此,了解这些相互关联的信号级联将为开发提高作物抗逆性的创新策略铺平道路,从而促进面对气候变化的可持续农业。
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引用次数: 0
SLAMF9 aggravates myocardial ischemia reperfusion injury through activating the hippo-yap pathway SLAMF9通过激活海马-叶波通路加重心肌缺血再灌注损伤。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-16 DOI: 10.1016/j.bbagen.2025.130821
Tingting Liu , Xiuli Guo , Yanhua Fu , Weili Zhang

Background

The objective was to investigate the impact of signaling lymphocyte activation molecule family member 9 (SLAMF9) on myocardial infarction (MI) and its mechanisms.

Methods

SLAMF9 expression in MI rats was firstly measured. SLAMF9 effect on cardiac functions, myocardial fibrosis, cardiomyocyte hypertrophy, cardiomyocyte apoptosis and inflammation in MI rats was explored using echocardiography, HE staining, masson staining, wheat germ agglutinin staining, western blot, TUNEL staining and qRT-PCR. Meanwhile, SLAMF9 effect on the viability, apoptosis, and inflammation in H9C2 cells was investigated by CCK-8 assay, TUNEL staining and western blot. Moreover, the potential mechanisms of SLAMF9 were investigated using western blot, ELISA and TUNEL staining after different treatment.

Results

SLAMF9 expression was upregulated in MI rats. SLAMF9 knockdown ameliorated heart damage, cardiomyocyte apoptosis and inflammatory response in MI rats. Similarly, SLAMF9 silencing in macrophages attenuated the apoptosis and inflammatory response in H/R-induced H9C2 cells. Moreover, SLAMF9 knockdown inhibited Hippo-Yap pathway in MI in vitro and in vivo. Besides, SLAMF9 knockdown in macrophages suppressed the activation of Hippo-Yap pathway in H9C2 cells by inhibiting TNF-α release. Additionally, LATS1 overexpression in H9C2 cells reversed the effect of SLAMF9 silencing on the apoptosis and inflammatory response in H/R-induced H9C2 cells. Meanwhile, PY-60 treatment in H9C2 cells reversed the effect of SLAMF9 overexpression on the apoptosis and inflammatory response in H/R-induced H9C2 cells.

Conclusion

The absence of SLAMF9 led to a reduction in TNF-α secretion in macrophages, consequently repressing Hippo-Yap pathway in cardiomyocytes, and ultimately ameliorating myocardial damage, cardiomyocyte apoptosis and inflammation in MI.
背景:目的是研究信号淋巴细胞活化分子家族成员9 (SLAMF9)对心肌梗死(MI)的影响及其机制。方法:首先测定心肌梗死大鼠中SLAMF9的表达。采用超声心动图、HE染色、masson染色、小麦胚凝集素染色、western blot、TUNEL染色、qRT-PCR等方法探讨SLAMF9对心肌梗死大鼠心功能、心肌纤维化、心肌细胞肥大、心肌细胞凋亡及炎症的影响。同时通过CCK-8法、TUNEL染色和western blot检测SLAMF9对H9C2细胞活力、凋亡和炎症的影响。此外,采用western blot、ELISA和TUNEL染色等方法研究不同处理后SLAMF9的潜在作用机制。结果:心肌梗死大鼠中SLAMF9表达上调。SLAMF9敲低可改善心肌梗死大鼠的心脏损伤、心肌细胞凋亡和炎症反应。同样,巨噬细胞中SLAMF9的沉默可以减轻H/ r诱导的H9C2细胞的凋亡和炎症反应。此外,在体外和体内实验中,SLAMF9敲低可抑制心肌梗死的Hippo-Yap通路。此外,巨噬细胞中SLAMF9敲低可通过抑制TNF-α释放抑制H9C2细胞中hipo - yap通路的激活。此外,LATS1在H9C2细胞中的过表达逆转了SLAMF9沉默对H/ r诱导的H9C2细胞凋亡和炎症反应的影响。同时,PY-60处理H9C2细胞逆转了SLAMF9过表达对H/ r诱导的H9C2细胞凋亡和炎症反应的影响。结论:SLAMF9缺失导致巨噬细胞分泌TNF-α减少,从而抑制心肌细胞的Hippo-Yap通路,最终改善心肌梗死的心肌损伤、心肌细胞凋亡和炎症。
{"title":"SLAMF9 aggravates myocardial ischemia reperfusion injury through activating the hippo-yap pathway","authors":"Tingting Liu ,&nbsp;Xiuli Guo ,&nbsp;Yanhua Fu ,&nbsp;Weili Zhang","doi":"10.1016/j.bbagen.2025.130821","DOIUrl":"10.1016/j.bbagen.2025.130821","url":null,"abstract":"<div><h3>Background</h3><div>The objective was to investigate the impact of signaling lymphocyte activation molecule family member 9 (SLAMF9) on myocardial infarction (MI) and its mechanisms.</div></div><div><h3>Methods</h3><div>SLAMF9 expression in MI rats was firstly measured. SLAMF9 effect on cardiac functions, myocardial fibrosis, cardiomyocyte hypertrophy, cardiomyocyte apoptosis and inflammation in MI rats was explored using echocardiography, HE staining, masson staining, wheat germ agglutinin staining, western blot, TUNEL staining and qRT-PCR. Meanwhile, SLAMF9 effect on the viability, apoptosis, and inflammation in H9C2 cells was investigated by CCK-8 assay, TUNEL staining and western blot. Moreover, the potential mechanisms of SLAMF9 were investigated using western blot, ELISA and TUNEL staining after different treatment.</div></div><div><h3>Results</h3><div>SLAMF9 expression was upregulated in MI rats. SLAMF9 knockdown ameliorated heart damage, cardiomyocyte apoptosis and inflammatory response in MI rats. Similarly, SLAMF9 silencing in macrophages attenuated the apoptosis and inflammatory response in H/R-induced H9C2 cells. Moreover, SLAMF9 knockdown inhibited Hippo-Yap pathway in MI in vitro and in vivo. Besides, SLAMF9 knockdown in macrophages suppressed the activation of Hippo-Yap pathway in H9C2 cells by inhibiting TNF-α release. Additionally, LATS1 overexpression in H9C2 cells reversed the effect of SLAMF9 silencing on the apoptosis and inflammatory response in H/R-induced H9C2 cells. Meanwhile, PY-60 treatment in H9C2 cells reversed the effect of SLAMF9 overexpression on the apoptosis and inflammatory response in H/R-induced H9C2 cells.</div></div><div><h3>Conclusion</h3><div>The absence of SLAMF9 led to a reduction in TNF-α secretion in macrophages, consequently repressing Hippo-Yap pathway in cardiomyocytes, and ultimately ameliorating myocardial damage, cardiomyocyte apoptosis and inflammation in MI.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130821"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092288","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}
引用次数: 0
Decoding the calcium signal: Structural insights into CBL-CIPK pathway in plants 解码钙信号:植物CBL-CIPK通路的结构见解。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-13 DOI: 10.1016/j.bbagen.2025.130819
Subhash Chandra Bihani , Tarushi , Ashish Kumar Srivastava
Calcium (Ca2+) signaling in plants is a major pathway in transducing diverse environmental stimuli. Calcineurin B-like proteins (CBLs) are one of the unique groups of Ca2+ sensors that transduce the Ca2+ signals by interacting with plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). In recent years, structure-function studies have provided key insights into the molecular basis of CBL-CIPK signaling and their interactions with the target proteins. The crystal structures of CBL2 and CBL4 have elucidated the architecture of non-canonical EF hands and provided the rationale for Ca2+ binding by CBLs. The molecular basis of interaction of the regulatory domain of CIPKs with CBLs has been established, providing rationale for CBL-mediated activation of CIPKs. The molecular mechanism of fine regulation of CIPK activity under non-stressed conditions and full activation under stressed conditions has been established using crystal structures of CIPK23 and CIPK24. Recently, high-resolution CryoEM structures of Arabidopsis and rice SOS1 led to a comprehensive understanding of its regulation and ion transport mechanism. In this review, major advances in understanding the structural basis of Ca2+ sensing by CBLs, molecular determinants of CIPK activation, and subsequent phosphorylation of target proteins are discussed. Remaining questions that need to be answered for a holistic understanding of the CBL-CIPK network are also discussed.
植物钙(Ca2+)信号是多种环境刺激信号转导的主要途径。钙调磷酸酶b样蛋白(CBLs)是一种独特的Ca2+传感器,通过与植物特异性蛋白激酶(称为cbll相互作用蛋白激酶(CIPKs))相互作用来转导Ca2+信号。近年来,结构-功能研究为了解CBL-CIPK信号的分子基础及其与靶蛋白的相互作用提供了重要的见解。CBL2和CBL4的晶体结构阐明了非规范EF手的结构,并为CBLs结合Ca2+提供了理论依据。CIPKs调控域与CBLs相互作用的分子基础已经建立,为CBLs介导的CIPKs激活提供了理论基础。利用CIPK23和CIPK24的晶体结构,建立了非应力条件下CIPK活性精细调控和应力条件下完全活化的分子机制。近年来,拟南芥和水稻SOS1的高分辨率CryoEM结构使人们对其调控和离子转运机制有了全面的了解。在这篇综述中,主要的进展,了解Ca2+传感的CBLs的结构基础,CIPK活化的分子决定因素,以及随后的磷酸化靶蛋白进行了讨论。本文还讨论了为全面理解CBL-CIPK网络而需要回答的剩余问题。
{"title":"Decoding the calcium signal: Structural insights into CBL-CIPK pathway in plants","authors":"Subhash Chandra Bihani ,&nbsp;Tarushi ,&nbsp;Ashish Kumar Srivastava","doi":"10.1016/j.bbagen.2025.130819","DOIUrl":"10.1016/j.bbagen.2025.130819","url":null,"abstract":"<div><div>Calcium (Ca<sup>2+</sup>) signaling in plants is a major pathway in transducing diverse environmental stimuli. Calcineurin B-like proteins (CBLs) are one of the unique groups of Ca<sup>2+</sup> sensors that transduce the Ca<sup>2+</sup> signals by interacting with plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). In recent years, structure-function studies have provided key insights into the molecular basis of CBL-CIPK signaling and their interactions with the target proteins. The crystal structures of CBL2 and CBL4 have elucidated the architecture of non-canonical EF hands and provided the rationale for Ca<sup>2+</sup> binding by CBLs. The molecular basis of interaction of the regulatory domain of CIPKs with CBLs has been established, providing rationale for CBL-mediated activation of CIPKs. The molecular mechanism of fine regulation of CIPK activity under non-stressed conditions and full activation under stressed conditions has been established using crystal structures of CIPK23 and CIPK24. Recently, high-resolution CryoEM structures of Arabidopsis and rice SOS1 led to a comprehensive understanding of its regulation and ion transport mechanism. In this review, major advances in understanding the structural basis of Ca<sup>2+</sup> sensing by CBLs, molecular determinants of CIPK activation, and subsequent phosphorylation of target proteins are discussed. Remaining questions that need to be answered for a holistic understanding of the CBL-CIPK network are also discussed.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130819"},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075771","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}
引用次数: 0
Cyanobacterial KdpD modulates in vivo and in vitro activities of a membrane-anchored histidine kinase 蓝藻KdpD调节膜锚定组氨酸激酶的体内和体外活性。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-11 DOI: 10.1016/j.bbagen.2025.130817
Anand Ballal , Shree Kumar Apte
The prokaryotic KdpATPAse complex, encoded by the kdpABC operon, is an inducible, high-affinity K+ transporter. In E. coli, the operon is transcriptionally regulated by a two-component sensor-kinase response-regulator system, constituted by the KdpD and KdpE proteins. In contrast, cyanobacteria exhibit a truncated kdpD gene that encodes a KdpD homolog that is similar to the N-terminal domain (NTD) of E. coli KdpD, but lacks the transmitter, histidine kinase-containing, C-terminal domain (CTD). Here we show that the cyanobacterium Anabaena sp. strain L-31 constitutively transcribes the short kdpD gene, but synthesizes KdpATPase only during potassium starvation. However, unlike E. coli., expression of the kdpD gene remains unaffected by K+ limitation in Anabaena. To gain insight into the possible role of Anabaena KdpD, the chimeric Anacoli KdpD protein, wherein the NTD of E. coli KdpD was replaced with Anabaena KdpD, was functionally analyzed. Detailed investigation has revealed that the Anacoli KdpD (a) responds to a much lower threshold of external K+ than the E. coli KdpD (b) exhibits much reduced ability to induce kdp in response to ionic osmolytes than E. coli KdpD, and is therefore unable to sustain optimal growth in the presence of these osmolytes and (c) displays higher in vitro phosphatase activity than the wild type E. coli KdpD. Thus, Anabaena KdpD modulates properties of E. coli KdpD-CTD in a manner that is quite distinct from the E. coli KdpD-NTD. Based on these evidences, a model for kdp regulation by the short KdpD is proposed.
由kdpABC操纵子编码的原核生物KdpATPAse复合物是一种可诱导的高亲和力K+转运体。在大肠杆菌中,操纵子受由KdpD和KdpE蛋白组成的双组分传感器-激酶反应调节系统的转录调节。相比之下,蓝藻细菌表现出截断的kdpD基因,该基因编码的kdpD同源物与大肠杆菌kdpD的n端结构域(NTD)相似,但缺乏递质,含组氨酸激酶的c端结构域(CTD)。本研究表明,蓝藻Anabaena菌株L-31可组成性地转录kdpD短基因,但仅在缺钾状态下合成KdpATPase。然而,不像大肠杆菌。, kdpD基因的表达不受K+限制的影响。为了深入了解Anabaena KdpD的可能作用,我们对大肠杆菌KdpD的NTD被Anabaena KdpD取代的嵌合Anacoli KdpD蛋白进行了功能分析。详细的研究表明,Anacoli KdpD (a)对外部K+的反应阈值比大肠杆菌KdpD低得多(b)在离子渗透物诱导KdpD的能力比大肠杆菌KdpD低得多,因此在这些渗透物存在下生长较慢;(c)在体外磷酸酶活性比野生型大肠杆菌KdpD高。因此,Anabaena KdpD以一种与大肠杆菌KdpD- ntd截然不同的方式调节大肠杆菌KdpD- ctd的特性。在此基础上,本文提出了一个由短KdpD调控的kdp模型。
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引用次数: 0
There is more to scanning than meets the eye: Raster Image Correlation Spectroscopy 还有更多的扫描比满足眼睛:光栅图像相关光谱学。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-10 DOI: 10.1016/j.bbagen.2025.130818
Irene Gialdini , Jelle Hendrix , Don C. Lamb
Raster Image Correlation Spectroscopy (RICS) is a confocal image analysis method that can measure the diffusion and interactions of fluorescently labeled molecules in real time in solution and in living cells. RICS is easy to implement on commercial confocal microscopes and allows detailed investigations of complex biological systems and pathways. The method is especially robust for measurements in living cells using commonly used labels such as fluorescent proteins. Moreover, since its invention in 2005, the robustness and applicability of RICS has been significantly increased to allow, e.g., straightforward kinetic analyses, advanced image segmentation, parameter mapping, and multi-species analysis. In this review, we describe the methodological principles of RICS in a manner that is accessible to a broad readership, position RICS in relation to other fluorescence fluctuation techniques, highlight recent methodological advances and present exemplary applications of the method. With this review, we hope to facilitate the implementation of this powerful method into the everyday repertoire of confocal imaging approaches.
光栅图像相关光谱(RICS)是一种共聚焦图像分析方法,可以实时测量荧光标记分子在溶液和活细胞中的扩散和相互作用。RICS很容易在商用共聚焦显微镜上实现,并且可以对复杂的生物系统和途径进行详细的研究。该方法尤其适用于使用荧光蛋白等常用标记对活细胞进行测量。此外,自2005年发明以来,RICS的鲁棒性和适用性得到了显著提高,可以进行直接的动力学分析、高级图像分割、参数映射和多物种分析。在这篇综述中,我们以一种通俗易懂的方式描述了RICS的方法学原理,将RICS与其他荧光波动技术进行了比较,强调了最近的方法学进展,并介绍了该方法的示例应用。通过这篇综述,我们希望促进这种强大的方法在共聚焦成像方法中的日常应用。
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引用次数: 0
LACTB promotes cell differentiation and inhibits cell proliferation in colorectal cancer LACTB促进结直肠癌细胞分化,抑制结直肠癌细胞增殖。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-10 DOI: 10.1016/j.bbagen.2025.130816
Lili Ma , Guan Huang , Chun Lin , Xiaoqing Li , Chao Liu , Weiye Huang , Qingling Zhang , Yang Luo
This study aims at exploring the role of LACTB on colorectal cancer (CRC) cell differentiation. In this study, 143 colorectal cancer tissue samples were collected for analyzing the correlation between LACTB level and clinical information. Another 24 recent cases and adjacent tissues underwent qPCR, Western blot, and immunohistochemistry (IHC) to detect LACTB expression. The differentiation and proliferation of CRC cells were evaluated by AKP levels, E-cadherin expression, cell viability, colony formation, EdU assay, and cell cycle. Subcutaneous models explored LACTB's pro-differentiation effects. The glandular-like structures of tumor were observed by HE staining, immunofluorescence detection of microvilli proteins, and transmission electron microscopy. Our results showed that LACTB expression in colorectal cancer tissues was lower than that in adjacent normal tissues. Higher LACTB expression was correlated with slower tumor progression, better prognosis and higher differentiation degree. Overexpressing LACTB in CRC cells enhanced differentiation markers level (AKP and E-cadherin), while inhibited cell proliferation and colony formation, induced cell cycle arrest. Conversely, LACTB knockdown had an opposite effect. Subcutaneous xenograft tumor model suggested that LACTB overexpression inhibited tumor growth, induced tissue differentiation and glandular-like structures formation. Collectively, our results show that LACTB overexpression promotes cell differentiation and inhibits cell proliferation in CRC cells, which may serve as a therapy target for CRC.
本研究旨在探讨LACTB在结直肠癌(CRC)细胞分化中的作用。本研究收集143例结直肠癌组织样本,分析其乳酸泌乳酶水平与临床信息的相关性。另外24例近期病例及邻近组织采用qPCR、Western blot和免疫组化(IHC)检测LACTB表达。通过AKP水平、E-cadherin表达、细胞活力、集落形成、EdU测定和细胞周期评价结直肠癌细胞的分化和增殖。皮下模型探讨了LACTB的促分化作用。HE染色、微绒毛蛋白免疫荧光检测、透射电镜观察肿瘤腺样结构。我们的研究结果显示,结直肠癌组织中LACTB的表达低于邻近正常组织。高表达与肿瘤进展慢、预后好、分化程度高相关。在结直肠癌细胞中过表达LACTB可提高分化标志物(AKP和E-cadherin)水平,同时抑制细胞增殖和集落形成,诱导细胞周期阻滞。相反,敲低LACTB具有相反的效果。皮下异种移植瘤模型表明,过表达乳酸泌乳b抑制肿瘤生长,诱导组织分化和腺样结构形成。综上所述,我们的研究结果表明,在结直肠癌细胞中,LACTB过表达促进细胞分化并抑制细胞增殖,可能是结直肠癌的治疗靶点。
{"title":"LACTB promotes cell differentiation and inhibits cell proliferation in colorectal cancer","authors":"Lili Ma ,&nbsp;Guan Huang ,&nbsp;Chun Lin ,&nbsp;Xiaoqing Li ,&nbsp;Chao Liu ,&nbsp;Weiye Huang ,&nbsp;Qingling Zhang ,&nbsp;Yang Luo","doi":"10.1016/j.bbagen.2025.130816","DOIUrl":"10.1016/j.bbagen.2025.130816","url":null,"abstract":"<div><div>This study aims at exploring the role of LACTB on colorectal cancer (CRC) cell differentiation. In this study, 143 colorectal cancer tissue samples were collected for analyzing the correlation between LACTB level and clinical information. Another 24 recent cases and adjacent tissues underwent qPCR, Western blot, and immunohistochemistry (IHC) to detect LACTB expression. The differentiation and proliferation of CRC cells were evaluated by AKP levels, E-cadherin expression, cell viability, colony formation, EdU assay, and cell cycle. Subcutaneous models explored LACTB's pro-differentiation effects. The glandular-like structures of tumor were observed by HE staining, immunofluorescence detection of microvilli proteins, and transmission electron microscopy. Our results showed that LACTB expression in colorectal cancer tissues was lower than that in adjacent normal tissues. Higher LACTB expression was correlated with slower tumor progression, better prognosis and higher differentiation degree. Overexpressing LACTB in CRC cells enhanced differentiation markers level (AKP and E-cadherin), while inhibited cell proliferation and colony formation, induced cell cycle arrest. Conversely, LACTB knockdown had an opposite effect. Subcutaneous xenograft tumor model suggested that LACTB overexpression inhibited tumor growth, induced tissue differentiation and glandular-like structures formation. Collectively, our results show that LACTB overexpression promotes cell differentiation and inhibits cell proliferation in CRC cells, which may serve as a therapy target for CRC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130816"},"PeriodicalIF":2.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958318","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}
引用次数: 0
Unraveling architectural RNAs: Structural and functional blueprints of membraneless organelles and strategies for genome-scale identification 结构rna:一类作为无膜细胞器支架的长链非编码rna。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-08 DOI: 10.1016/j.bbagen.2025.130815
Naoko Fujiwara, Tsuyoshi Ueno, Tomohiro Yamazaki, Tetsuro Hirose
Architectural RNAs (arcRNAs) are long noncoding RNAs that serve as structural scaffolds for membraneless organelles (MLOs), facilitating cellular organization and dynamic responses to stimuli. Acting as blueprints for MLO assembly, arcRNAs recruit specific proteins and nucleic acids to establish and maintain the internal structure of MLOs while coordinating their spatial relationships with other organelles. This organized framework enables precise spatiotemporal regulation, allowing for targeted control of transcription, RNA processing, and cellular responses to stress. Notably, arcRNAs exhibit the “semi-extractable” feature, a property derived from their stable binding to cellular structures, making them partially resistant to conventional RNA extraction methods. This unique feature serves as a useful criterion for identifying novel arcRNAs, providing an opportunity to accelerate research in long noncoding RNAs and deepen our understanding of their functional roles in cellular processes.
建筑rna (arcRNAs)是一种长链非编码rna,作为无膜细胞器(MLOs)的结构支架,促进细胞组织和对刺激的动态反应。arcrna作为MLO组装的蓝图,招募特定的蛋白质和核酸来建立和维持MLO的内部结构,同时协调其与其他细胞器的空间关系。这种有组织的框架能够实现精确的时空调节,允许有针对性地控制转录,RNA加工和细胞对应激的反应。值得注意的是,arcRNAs表现出“半可提取”的特征,这一特性源于它们与细胞结构的稳定结合,使它们对传统的RNA提取方法具有部分抗性。这种独特的特征可以作为鉴定新型arcrna的有用标准,为加速长链非编码rna的研究提供了机会,并加深了我们对其在细胞过程中的功能作用的理解。
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Biochimica et biophysica acta. General subjects
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