Biochimica et biophysica acta. General subjects最新文献

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Plasma-activated medium disrupts intercellular barrier function in HaCaT cells by suppressing claudin-1 expression via clathrin-dependent endocytosis 血浆活化培养基通过网格蛋白依赖内吞作用抑制claudin-1的表达,破坏HaCaT细胞间屏障功能
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI: 10.1016/j.bbagen.2025.130826
Chika Miyamoto , Yuta Yoshino , Hiromasa Tanaka , Hirokazu Hara , Satoshi Endo , Akira Ikari
{"title":"Plasma-activated medium disrupts intercellular barrier function in HaCaT cells by suppressing claudin-1 expression via clathrin-dependent endocytosis","authors":"Chika Miyamoto ,&nbsp;Yuta Yoshino ,&nbsp;Hiromasa Tanaka ,&nbsp;Hirokazu Hara ,&nbsp;Satoshi Endo ,&nbsp;Akira Ikari","doi":"10.1016/j.bbagen.2025.130826","DOIUrl":"10.1016/j.bbagen.2025.130826","url":null,"abstract":"<div><div>The skin plays a critical role in protecting against water loss from the inside and pathogen invasion from the outside. The expression levels and localization of claudin-1 (CLDN1) are responsible for the tight junction (TJ) barrier function in the epidermis. Nonthermal atmospheric pressure plasma (NTAPP) has recently received attention as a novel tool in life sciences, including dermatology. NTAPP application showed useful effects on the skin, including antimicrobial activity, wound healing promotion, and anticancer activity for melanoma. However, it remains unknown how NTAPP indirect irradiation affects skin cells. In this study, we used the human epidermal keratinocyte HaCaT cells to clarify the effect of NTAPP-irradiated medium (PAM) on the epidermal TJ barrier function. Treatment with 30 % of the medium irradiated no distance from NTAPP (PAM0) significantly decreased the expression levels of CLDN1 protein. PAM0 significantly decreased the localization of CLDN1 in the cell-cell contact area. After PAM0 treatment, further culture without PAM0 significantly restored the expression and localization of CLDN1 to the same level as in the control cells. The PAM0-induced changes in protein expression and localization of CLDN1 involve lysosome degradation via a clathrin-dependent endocytosis. Treatment with PAM0 decreases transepithelial electrical resistance and increases the intercellular permeability of low-molecular-weight compounds but not high-molecular-weight compounds. The present study shows that treatment with PAM0 weakens intercellular permeability by decreasing the TJ localization of CLDN1 protein in human epidermal keratinocytes. The technology using NTAPP may be useful to promote transdermal absorption of drugs that are difficult to permeate into the body.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130826"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169831","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
Computational modelling of olfactory receptors 嗅觉受体的计算模型
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI: 10.1016/j.bbagen.2025.130825
Chiemela S. Odoemelam, Volker Steuber, Michael Schmuker
{"title":"Computational modelling of olfactory receptors","authors":"Chiemela S. Odoemelam,&nbsp;Volker Steuber,&nbsp;Michael Schmuker","doi":"10.1016/j.bbagen.2025.130825","DOIUrl":"10.1016/j.bbagen.2025.130825","url":null,"abstract":"<div><div>Olfactory receptors (ORs), the largest subfamily of G protein-coupled receptors, are essential for detecting and interpreting environmental odorants in animals. Understanding their function is crucial for deciphering olfactory perception and exploring emerging roles in non-olfactory systems. With the recent surge in available sequence data and AI-based structural predictions, computational modelling has become indispensable for investigating OR structure, ligand binding, and activation mechanisms. This review provides a comprehensive overview of computational approaches used in OR research, including homology modelling, molecular docking, molecular dynamics simulations, free energy calculations, pharmacophore modelling, virtual screening, and machine learning-based predictions. Both ligand-based and structure-based pharmacophore modelling are discussed in detail, highlighting their respective applications, strengths, and limitations. While structure-based approaches have gained prominence due to advances in receptor structure prediction tools like AlphaFold, ligand-based pharmacophore modelling remains valuable in scenarios where structural data are limited or uncertain. Case studies illustrate how these techniques have been applied to identify novel OR–ligand interactions, explore receptor dynamics, and support drug discovery. Collectively, these computational strategies offer powerful tools for decoding OR function, guiding experimental validation, and expanding our understanding of olfactory signalling in health and disease.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130825"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169830","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
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
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-05-16 DOI: 10.1016/j.bbagen.2025.130821
Tingting Liu , Xiuli Guo , Yanhua Fu , Weili Zhang
{"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":"2025-07-01","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
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
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-05-17 DOI: 10.1016/j.bbagen.2025.130820
Tanashvi Seth, Shruti Saxena, Barkha Ravi, Girdhar K. Pandey
{"title":"Mastering the plant growth symphony: The interplay between calcium sensing machinery and phytohormone signaling during abiotic stress","authors":"Tanashvi Seth,&nbsp;Shruti Saxena,&nbsp;Barkha Ravi,&nbsp;Girdhar K. Pandey","doi":"10.1016/j.bbagen.2025.130820","DOIUrl":"10.1016/j.bbagen.2025.130820","url":null,"abstract":"<div><div>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 (Ca<sup>2+</sup>) signaling and phytohormonal regulation in plant stress responses. Ca<sup>2+</sup>, 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 Ca<sup>2+</sup>-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.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130820"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101223","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
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
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-05-10 DOI: 10.1016/j.bbagen.2025.130818
Irene Gialdini , Jelle Hendrix , Don C. Lamb
{"title":"There is more to scanning than meets the eye: Raster Image Correlation Spectroscopy","authors":"Irene Gialdini ,&nbsp;Jelle Hendrix ,&nbsp;Don C. Lamb","doi":"10.1016/j.bbagen.2025.130818","DOIUrl":"10.1016/j.bbagen.2025.130818","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130818"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955920","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
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-05-08 DOI: 10.1016/j.bbagen.2025.130815
Naoko Fujiwara, Tsuyoshi Ueno, Tomohiro Yamazaki, Tetsuro Hirose
{"title":"Unraveling architectural RNAs: Structural and functional blueprints of membraneless organelles and strategies for genome-scale identification","authors":"Naoko Fujiwara,&nbsp;Tsuyoshi Ueno,&nbsp;Tomohiro Yamazaki,&nbsp;Tetsuro Hirose","doi":"10.1016/j.bbagen.2025.130815","DOIUrl":"10.1016/j.bbagen.2025.130815","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130815"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973739","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
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
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub 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
{"title":"N-glycosylation of CD4+ T cell changes with the development in Graves' disease and is sensitive to methimazole treatment","authors":"Sara Trzos ,&nbsp;Marta Szewczyk ,&nbsp;Paweł Link-Lenczowski ,&nbsp;Grzegorz Sokołowski ,&nbsp;Małgorzata Trofimiuk-Müldner ,&nbsp;Katarzyna Bocian ,&nbsp;Ewa Pocheć","doi":"10.1016/j.bbagen.2025.130824","DOIUrl":"10.1016/j.bbagen.2025.130824","url":null,"abstract":"<div><div>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. <em>N</em>-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<sup>+</sup>CD25<sup>−</sup> cells and those expressing the CD25 late activation marker (CD4<sup>+</sup>CD25<sup>+</sup>). MALDI-Tof MS was used for analysis of <em>N-</em>linked glycans, and the expression of glycosyltransferases was determined by RT-qPCR. The <em>N</em>-glycosylation profile of CD4<sup>+</sup> cell subpopulations differed in the ratio of the complex-to-oligomannose <em>N</em>-glycans in GD. Complex <em>N</em>-glycans are partially replaced by oligomannose forms, and their structure is shortened by agalactosylation in CD4<sup>+</sup>CD25<sup>−</sup> cells from GD. The rearrangement of <em>N</em>-glycans in CD4<sup>+</sup>CD25<sup>+</sup> cells has the opposite direction, namely the ratio is shifted towards complex structures in GD. The changes in the <em>N</em>-glycan profile were reflected partly in <em>MGAT5</em> and <em>FUT8</em> expression. Methimazole to some extent normalized the glycosyltransferase levels and affected the <em>N</em>-linked glycans profile. Our study shows <em>N</em>-glycosylation changes in CD4<sup>+</sup> 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.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130824"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156081","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
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
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub 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
{"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":"2025-07-01","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
Ferroptosis induction, androgen biosynthesis disruption and prostate cancer suppression by androgen and vitamin D combination 雄激素和维生素D联合诱导铁下垂、雄激素生物合成中断和前列腺癌抑制。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-05-28 DOI: 10.1016/j.bbagen.2025.130828
Bobae Park, Subash Khadka, Jungmi Ahn, Jacqueline Vaquiz, Okunola Igbekoyi, Chung S. Song, Bandana Chatterjee
{"title":"Ferroptosis induction, androgen biosynthesis disruption and prostate cancer suppression by androgen and vitamin D combination","authors":"Bobae Park,&nbsp;Subash Khadka,&nbsp;Jungmi Ahn,&nbsp;Jacqueline Vaquiz,&nbsp;Okunola Igbekoyi,&nbsp;Chung S. Song,&nbsp;Bandana Chatterjee","doi":"10.1016/j.bbagen.2025.130828","DOIUrl":"10.1016/j.bbagen.2025.130828","url":null,"abstract":"<div><div>Prostate cancer regression by hormonal vitamin D<sub>3</sub>(calcitriol) is clinically untenable despite its well-documented anticancer effects in experimental models, since supraphysiologic dosing of calcitriol required in clinical settings causes hypercalcemia and other toxicities. We show that subnanomolar/low-nanomolar calcitriol, while non-inhibitory on its own, inhibited CRPC cells upon co-treatment with androgen (5α-DHT) at a physiologic level, evident from G1/S cell cycle arrest, induction of p21/Cip1, blockade of clonal cell growth, retardation of proliferation, migration and invasion of cells <em>in vitro</em>, and xenograft growth suppression <em>in vivo</em>. AKR1D1, an androgen-inactivating 5β-reductase, was upregulated &gt;30-fold upon calcitriol/DHT co-treatment, while each hormone individually did not induce AKR1D1. In contrast, HSD3β1, a key enzyme for androgen biosynthesis, was upregulated &gt;12-fold by calcitriol, which was blocked by DHT co-treatment. Elevated AKR1D1 and reduced HSD3β1 would lower intracellular androgens and contribute to CRPC repression. Autophagy mediated ferroptosis (ferritinophagy) paralleled CRPC growth inhibition by the hormone combination –indicated by LC3B induction, ferritin reduction, and upregulation of mRNAs encoding NCOA4, ALOX-5 and PTGS2 which are core participants in ferroptosis. The combination treatment caused lipid peroxidation, evident from the fluorescence shift of C11-BODIPY(581/591)-labeled cells from red to green, and from elevated malondialdehyde. GPX4 - an antioxidant peroxidase and ferroptosis regulator – was downregulated. Bipolar androgen therapy employing supraphysiologic testosterone is under clinical evaluation for efficacy against treatment-resistant metastatic CRPC, although the high androgen dose raises safety concerns. Vitamin D and androgen administered concurrently at physiologic levels may offer a superior alternative for arresting CRPC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130828"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186431","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
Tryptophan enforced alg-iron oxide nanoconjugates: A potential evalution for synergistic cancer therapy 色氨酸强化海藻氧化铁纳米缀合物:对协同癌症治疗的潜在评价
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-07-01 Epub Date: 2025-06-04 DOI: 10.1016/j.bbagen.2025.130829
Amy Sarah Benjamin , Sunita Nayak
{"title":"Tryptophan enforced alg-iron oxide nanoconjugates: A potential evalution for synergistic cancer therapy","authors":"Amy Sarah Benjamin ,&nbsp;Sunita Nayak","doi":"10.1016/j.bbagen.2025.130829","DOIUrl":"10.1016/j.bbagen.2025.130829","url":null,"abstract":"<div><div>The contribution of magnetic nanoparticles towards the diagnosis and therapy of cancer has seen an upward graph for the past decade owing to their excellent superparamagnetic properties and contrast imaging. The surface functionalization of these iron oxide nanoparticles plays a pivotal role in the toxicity, circulation, and agglomeration parameters of clinical translation. Natural-source-based sodium alginate is a very profound biomaterial used in all areas of tissue engineering. This paper aims to study the properties of alginate-coated iron oxide nanoparticles conjugated to the aromatic amino acid tryptophan for cancer targeting. The investigation involves fabrication of the conjugated nano-system followed by analysis of the physico-chemical properties using XRD and FT-IR, evaluation of its magnetic property using VSM which shows a good superparamagnetic behaviour, along with an excellent thermal stability as shown by TGA analysis. The hyperthermia activity of these particles shows a very good specific absorption rate followed by the antioxidant property of the nano-conjugate, which shows potential scavenging activity. The biocompatibility of these nanoparticles was studied on NIH-3T3 cell lines, which showed no toxic effects, thus making the nano-conjugate an efficient cancer-targeting and therapeutic agent for future cancer nanomedicine.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130829"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239564","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
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