Biochemistry and Biophysics Reports最新文献

{"title":"Heterohybridomas producing human immunoglobulin light chains using CD138-selected bone marrow cells","authors":"P. Zhou ,&nbsp;X. Ma ,&nbsp;S. Scalia ,&nbsp;D. Toskic ,&nbsp;X. Wu ,&nbsp;T. Fogaren ,&nbsp;Nancy Coady Lyons ,&nbsp;Luis del Pozo-Yauner ,&nbsp;R.L. Comenzo","doi":"10.1016/j.bbrep.2025.102017","DOIUrl":"10.1016/j.bbrep.2025.102017","url":null,"abstract":"<div><h3>Background</h3><div>Light chain research is hampered by lack of mammalian cell lines producing human light chains (FLC). Therefore, we used heterohybridoma (HH) technology to produce clones making FLC thereby providing tools to study light chain behavior.</div></div><div><h3>Methods</h3><div>Marrow CD138+ cells from patients with multiple myeloma (MM) and polyclonal gammopathy (PG) were selected, fused with B5-6 T cells and cultured in hypoxanthine-aminopterin-thymidine medium (HAT). HH clones were selected based on ELISA for human immunoglobulins and flow cytometry for intracellular (IC) FLC. We compared marrow cell counts and HH yields by diagnosis, evaluated clones making only FLC by flow and by dimer/monomer (D/M) ratios in vitro and in vivo, and sequenced FLC genes with RT-PCR.</div></div><div><h3>Results</h3><div>Marrows from 13 patients with active disease, 10 MM and 3 PG, were no different in mononuclear or CD138-selected cell counts. HH FLC clones (7 λ, 1 κ) were obtained from 5/10 MM and 2/3 PG; one PG case produced 2 HH FLC clones (one λ and one κ). Of the 10 MM cases, 8 had high risk cytogenetic features and 4 of the 8 produced HH clones while of the 3 PG cases 2 had negative cytogenetics and 1 had loss of IgH identified and produced an HH clone. Mononuclear (MNC) and CD138-selected cell numbers were markedly higher in the samples that enabled productive fusions. Median MFI for the 8 HH clones by IC flow for FLC was 9849 (range, 5344–27451) and median percentage of cells IC positive was 88 % (69–95). Medians of in vitro and in vivo FLC production were 47 μg/mL (9–80) per million cells after 2 days of culture and 66.4 μg/mL (16–1100) in NOD-SCID γ (NSG) mice 14 days after intraperitoneal (IP) implants of 2 × 10⁶ HH cells. Dimer/monomer ratio medians were 0.575 (0.08–0.939) in vitro and 0.91 (0.82–2.7) in vivo, values that were correlated (R² = 0.565) by two-tailed paired <em>t</em>-test with <em>P</em> &lt; 0.05.</div></div><div><h3>Conclusions</h3><div>B5-6 T HH producing human FLC were obtained from 50 % of MM and PG cases. High numbers of MNC and CD138+ cells enabled productive fusions. The HH clones produced FLC with easily appreciated dimers and monomers in vitro and in vivo. With IP in vivo implants after 2 weeks more dimers were seen than in short term cultures in vitro. These HH clones will be made available for study of FLC metabolism and testing of therapeutics designed to abrogate FLC production or enable FLC clearance in vivo.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102017"},"PeriodicalIF":2.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising impacts of Achillea spp., beyond A medicinal plant, against toxins, toxicities, and injuries: In vivo and in vitro mechanisms","authors":"Mohammad Mahdi Dabbaghi ,&nbsp;Mohammad Saleh Fadaei ,&nbsp;Maral Goldoozian ,&nbsp;Mohammad Reza Fadaei ,&nbsp;Vafa Baradaran Rahimi ,&nbsp;Vahid Reza Askari","doi":"10.1016/j.bbrep.2025.102023","DOIUrl":"10.1016/j.bbrep.2025.102023","url":null,"abstract":"<div><div>Natural toxins produced by various living organisms pose significant risks to health, food security, and environmental balance through inhalation, ingestion, and other exposure routes. This review focuses on the ameliorative effects of different <em>Achillea</em> species, which comprise over 130 perennial herbs known for their therapeutic properties. A systematic examination of data from Scopus, PubMed, and Web of Science was conducted, encompassing various studies without date restrictions, ensuring a comprehensive selection of articles based on full-text availability. The results of this study indicate that <em>Achillea millefolium</em> exhibits anti-hyperglycemic and anti-hyperlipidemic properties, enhances collagen proliferation regulation, suppresses inflammatory responses, and displays significant antioxidant activity. Similarly, <em>A. wilhelmsii</em> has been shown to have hepatoprotective effects, as evidenced by reduced malondialdehyde levels and increased total thiol concentrations. <em>A. fragrantissima</em> has also been demonstrated to have cardioprotective effects, with a decrease in inflammatory markers and edema levels. The protective benefits of other species within the <em>Achillea</em> genus extend to various toxins. This comprehensive review underscores the potential of <em>Achillea</em> species as natural remedies for combating toxicities and promoting health.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102023"},"PeriodicalIF":2.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fenugreek inhibits cathepsin G activity and suppresses the progression of malignant phenotypes in MCF-7 cells","authors":"Kazunari Tanigawa ,&nbsp;Takashi Tanikawa ,&nbsp;Masashi Kitamura ,&nbsp;Yasuhiro Hayashi ,&nbsp;Mitsuo Kiriya ,&nbsp;Yasuhiro Nakamura ,&nbsp;Akira Kawashima ,&nbsp;Yoko Fujiwara ,&nbsp;Riyo Morimoto-Kamata ,&nbsp;Naoki Ohkura ,&nbsp;Satoru Yui ,&nbsp;Ken Karasawa ,&nbsp;Ryosuke Nakamura ,&nbsp;Koichi Suzuki","doi":"10.1016/j.bbrep.2025.102021","DOIUrl":"10.1016/j.bbrep.2025.102021","url":null,"abstract":"<div><div>Spices and herbs, which are derived from natural botanical sources, contain many bioactive compounds and play an important role in human health. The general and specific health benefits of these spices and herbs include anti-inflammatory, antioxidant, and anti-tumorigenic activities. Previously, we showed that cathepsin G, which is a neutrophil-derived serine protease localized in human breast cancer tissues, promotes cancer metastasis via induction of platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) expression in MCF-7 human breast cancer cells. Therefore, although regulation of cathepsin G activity is thought to be important in human breast cancer progression, no compounds that inhibit the activity have been identified for therapeutic purposes. In this study, we screened 50 spice and herb extracts. Peppermint, clove, Sichuan pepper, and fenugreek exhibited strong inhibitory effects on cathepsin G activity and suppressed cathepsin G-induced MCF-7 cell aggregation.; importantly, fenugreek suppressed the increase in PAFAH1B2 expression. The IC₅₀ of 37.38 μg/mL of fenugreek extract that showed inhibitory effect on cathepsin G-induced malignant progression was 5.87 times lower than the concentration that exerted cytotoxic effect. Interestingly, quercetin and trigonelline contained in fenugreek inhibited cathepsin G activity and suppressed the induction of cell aggregation and PAFAH1B2 expression in human breast cancer cells. These results suggest that quercetin and trigonelline are partly responsible for the inhibitory effect of fenugreek on cathepsin G-induced malignant progression of human breast cancer cells. Our findings provide a new breast cancer treatment strategy targeting cathepsin G, and fenugreek may have synergistic effects when combined with therapeutic drugs.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102021"},"PeriodicalIF":2.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence prediction of carcinoembryonic antigen structure and interactions relevant for colorectal cancer","authors":"Ivan Shabo ,&nbsp;Erik Nordling ,&nbsp;Mirna Abraham-Nordling","doi":"10.1016/j.bbrep.2025.102024","DOIUrl":"10.1016/j.bbrep.2025.102024","url":null,"abstract":"<div><div>Carcinoembryonic antigen (CEA) is used as a biomarker for colorectal cancer. It is expressed during fetal development but in healthy adult cells the expression is low. Due to its size and the high degree of glycosylation, there are no structures available for mature CEA. By employing novel structure prediction methods, we aim to investigate CEA tertiary structure and interactions.</div><div>Alphafold 3 server has increased the accuracy of structure predictions and allows for modelling of glycans in proteins and complexes. Models were created for a monomeric CEA, dimeric CEA and for CEA in complex with the antibody Tusamitamab. The structure of the monomeric glycosylated CEA exhibit two bends, one in the domain interface B1–A2 and one in the domain interface B2-A3. The dimer structure pairs in a parallel manner, with direct contacts in the N and the A2 domains of the two chains. The complex of CEA with Tusamitamab closely resembles the EM structure of the complex that was released after the training of Alphafold 3 was completed.</div><div>Overall, the investigations give new angles to investigate for CEA. The predicted bend, primarily in the B2 and A3 domain interface, would allow for dimer formation of CEA from both the same cell as from adjacent cells and could help to explain the outstanding issue on how it can fulfil both tasks. The prediction of the antibody binding to CEA was accurate, the all-atom RMSD was 1.3 Å. This is encouraging for other antibody – protein complexes predictions as the complex structure was not part of the training set for Alphafold 3.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102024"},"PeriodicalIF":2.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A nanoluciferase complementation-based assay for monitoring β-arrestin2 recruitment to the dopamine D3 receptor","authors":"Viktor Burström ,&nbsp;Kuiying Xu ,&nbsp;Emilio Garro-Martínez ,&nbsp;Robert H. Mach ,&nbsp;Kristoffer Sahlholm ,&nbsp;Nibal Betari","doi":"10.1016/j.bbrep.2025.102019","DOIUrl":"10.1016/j.bbrep.2025.102019","url":null,"abstract":"<div><div>Luciferase complementation assays have emerged as a simple means of monitoring receptor-effector interactions in living cells in a time-resolved manner. Here, we describe a nanoluciferase complementation assay capable of reporting on β-arrestin2 recruitment to the human dopamine D₃ receptor (D₃R) upon its activation in intact HEK293T cells. Using this assay in time-resolved experiments, we detect differences in arrestin response termination rates between the endogenous agonist dopamine and the synthetic D₃R agonist FAUC-73. We also investigate the influence of exogenous GRK2 on β-arrestin2 recruitment to the D₃R. We find that, in contrast to the D₂R and D₄R, the potency of dopamine to induce arrestin recruitment to D₃R is not significantly influenced by GRK2 overexpression. In further agreement with a lack of GRK2 regulation of D₃R signalling and again contrary to the D₂R and D₄R, we do not observe dopamine-induced recruitment of GRK2 to D₃R. Conversely, dopamine concentration-dependently decreases the interaction between GRK2 and D₃R. Additionally, we examine both the Ser-9 and Gly-9 variants of the human D₃R, which, according to some earlier reports, differ in terms of dopamine affinity and functional potency. However, we find no difference in the concentration-response relationships between these two variants, neither when arrestin recruitment nor GRK2 interactions are studied. In summary, the present report demonstrates the utility of nanoluciferase complementation for studying D₃R pharmacology in living cells.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102019"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptomics of multiple sclerosis peripheral blood mononuclear cells explored potential biomarkers for the disease","authors":"Arman Mokaram Doust Delkhah","doi":"10.1016/j.bbrep.2025.102022","DOIUrl":"10.1016/j.bbrep.2025.102022","url":null,"abstract":"<div><h3>Background</h3><div>Despite their importance, blood RNAs have not been comprehensively studied as potential diagnostic markers for multiple sclerosis (MS). Herein, by the integration of GSE21942 and GSE203241 microarray profiles of peripheral blood mononuclear cells, this study explored potential biomarkers for the disease.</div></div><div><h3>Methods</h3><div>After identification of differentially expressed genes (DEGs), functional enrichment analyses were performed, and PPI and miRNA-mRNA regulatory networks were constructed. After implementing weighted gene co-expression network analysis (WGCNA) and discovering MS-specific modules, the converging results of differential expression analysis and WGCNA were subjected to machine learning methods. Lastly, the diagnostic performance of the prominent genes was evaluated by receiver operating characteristic (ROC) analysis.</div></div><div><h3>Results</h3><div><em>COPG1</em>, <em>RPN1</em>, and <em>KDM3B</em> were initially highlighted as potential biomarkers based on their acceptable diagnostic efficacy in the integrated data, as well as in both GSE141804 and GSE146383 datasets as external validation sets. However, given that they were downregulated in the integrated data while they were upregulated in the validation sets, they could not be considered as potential biomarkers for the disease. In addition to this inconsistency, evaluating their diagnostic performance in other external datasets (GSE247181, GSE59085, and GSE17393) did not reveal their diagnostic efficacy.</div></div><div><h3>Conclusions</h3><div>This study could not unveil promising blood biomarkers for MS, possibly due to a small sample size and unaccounted confounding factors. Considering PBMCs and blood specimens as valuable sources for the identification of biomarkers, further transcriptomic analyses are needed to discover potential biomarkers for the disease.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102022"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin alleviates myocardial infarction by inhibiting inflammation, and apoptosis and promoting endothelial cell proliferation","authors":"Ruochen Du ,&nbsp;Ying Guo ,&nbsp;Wanting Zhong ,&nbsp;Yuantao Gao ,&nbsp;Miaomiao Xu ,&nbsp;Chunfang Wang ,&nbsp;Yitong Yuan","doi":"10.1016/j.bbrep.2025.102014","DOIUrl":"10.1016/j.bbrep.2025.102014","url":null,"abstract":"<div><div>Gastrodin, a bioactive ingredient extracted from the Chinese herb Gastrodia gastrodia, has shown potential therapeutic effects in cardiovascular diseases, but its specific role in myocardial infarction is unclear. This study investigated the protective effect of gastrodin on myocardial infarction and its potential mechanism. By clamping the left coronary artery, we created a model of myocardial infarction in C57BL/6J mice. For 14 days, mice in the control and myocardial infarction groups received a daily dose of 100 mg/kg gastrodin. Gastrodin significantly improved cardiac dysfunction in mice with myocardial infarction, decreased heart weight/body weight (HW/BW) and heart weight/tibial length (HW/TL) ratios, and inhibited mRNA expression levels of cardiac fibrosis biomarkers (Collagen Type I (Col1), Collagen Type III (Col3), Matrix Metalloproteinase-2 (MMP-2), Matrix Metalloproteinase-9 (MMP-9)). In addition, gastrodin also inhibited the activity of apoptosis marker Caspase 3, decreased the Bax/Bcl2 mRNA ratio, decreased the expression of pro-inflammatory factors (Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6)) and pro-inflammatory adhesion molecule Monocyte Chemoattractant Protein-1 (MCP1), and promoted the expression of angiogenesis marker Cluster of Differentiation 31 (CD31). RNA sequencing and Rt-qPCR analysis showed that gastrodin treatment significantly up-regulated the expression of genes related to cell proliferation (Cyclin-Dependent Kinase 1 (CDK1), Threonine Tyrosine Kinase (TTK), Cyclin B2 (CCNB2), Polo-Like Kinase 1 (PLK1)), and promoted the proliferation of human aortic endothelial cells (HAECs). These findings suggest that gastrodin can effectively reduce the pathological changes of myocardial infarction by inhibiting inflammation, reducing apoptosis, and promoting endothelial cell proliferation, thus providing a new strategy for the prevention and treatment of myocardial infarction.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102014"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current literature support and opposition for therapeutic use of selenium supplementation in autoimmune thyroid conditions","authors":"Abhinav Nannapaneni,&nbsp;Victoria Wilson,&nbsp;Shahzaib Chughtai","doi":"10.1016/j.bbrep.2025.102013","DOIUrl":"10.1016/j.bbrep.2025.102013","url":null,"abstract":"<div><div>This systematic review investigates the correlation between selenium status and thyroid conditions, specifically focusing on autoimmune thyroid diseases (AITD) including Hashimoto's Thyroiditis (HT) and Graves' Disease (GD). After a meticulous analysis of 14 research studies, we explored the impact of selenium levels and supplementation on several thyroid-specific parameters and overall disease progression. Several studies indicated a notable inverse correlation between selenium deficiency and the prevalence and severity of AITD. In particular, HT patients showed consistent improvement with selenium supplementation, suggesting its potential as a therapeutic agent. However, the effect of selenium on GD was not as clear, with some studies indicating no significant correlation. These inconsistent effects demonstrate how nuanced AITD treatment must be. It also shows that selenium plays a varied role in thyroid health. The findings in this review serve as an example of how micronutrient intake is important in thyroid disease management. The nuances of these treatments support a need for more patient-centered and individualized treatment plans, which may be further helped by detailed research into proper dosing and administration strategies. Specific patient populations may benefit from selenium supplementation, though the variability in outcomes points to a need for vigilance in the clinical setting. Importantly, the ability to personalize supplementation depends on establishing a reliable method for detecting selenium deficiency or status. Future clinical guidelines should emphasize the necessity of a solid diagnostic framework that allows for precise monitoring, ensuring that selenium supplementation is appropriately justified and tailored to individual patient needs.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pterostilbene and resveratrol: Exploring their protective mechanisms against skin photoaging – A scoping review","authors":"Raveena Vaidheswary Muralitharan ,&nbsp;Siti Fathiah Masre ,&nbsp;Dayang Fredalina Basri ,&nbsp;Ahmad Rohi Ghazali","doi":"10.1016/j.bbrep.2025.102011","DOIUrl":"10.1016/j.bbrep.2025.102011","url":null,"abstract":"<div><div>Prolonged ultraviolet (UV) exposure depletes the skin's endogenous antioxidants, leading to photoaging. Exogenous antioxidants are essential to counter this, with stilbenes such as pterostilbene and resveratrol emerging as promising candidates due to their antioxidant, anti-inflammatory and anti-cancer properties. The current scoping review presents an overview of the evidence on the effects of pterostilbene and resveratrol on skin photoaging. A literature search was conducted using PubMed, Scopus, and Web of Science databases in April 2025. Original research articles that investigated the effects of pterostilbene and resveratrol on skin photoaging in cells, animals, or humans were included. 9 eligible articles were included in this review. The findings suggest that resveratrol significantly improves skin photoaging, while preliminary evidence indicates that pterostilbene may offer advantages over resveratrol. However, due to the limited research on pterostilbene, further studies are required to confirm its efficacy. Key considerations in establishing valid in vitro and in vivo models, alongside macroscopic and histologic features of photoaging, were also discussed. In conclusion, while resveratrol shows significant promise in combating skin photoaging, pterostilbene is still in the early exploration phases. Advancing to human trials is crucial to confirm the efficacy of these stilbenes in preventing and treating photoaging.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102011"},"PeriodicalIF":2.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis","authors":"Kenta Ouchi ,&nbsp;Takeshi Masuda ,&nbsp;Kou Yonemaru ,&nbsp;Kaori Isono ,&nbsp;Yuki Ohya ,&nbsp;Nobuaki Shiraki ,&nbsp;Masayoshi Tasaki ,&nbsp;Yukihiro Inomata ,&nbsp;Mitsuharu Ueda ,&nbsp;Takumi Era ,&nbsp;Shoen Kume ,&nbsp;Yukio Ando ,&nbsp;Hirofumi Jono","doi":"10.1016/j.bbrep.2025.102012","DOIUrl":"10.1016/j.bbrep.2025.102012","url":null,"abstract":"<div><div>Hereditary transthyretin (TTR) amyloidosis (ATTRv amyloidosis) is an autosomal dominant disease caused by various TTR mutations. Despite the fact that ATTR Tyr114Cys (p.Tyr134Cys) amyloidosis (tyrosine to cysteine at codon 114) exhibits poorer prognosis than other ATTRv amyloidosis and leads to death due to severe clinical symptoms, the molecular pathogenesis of ATTR Tyr114Cys amyloidosis is still largely unknown. In this study, we took advantage of ATTR Tyr114Cys amyloidosis-specific induced pluripotent stem (iPS) cells to differentiate into hepatocyte-like cells (Y114C-HLCs), which are mainly TTR producing cells, and elucidated their pathogenesis. We performed proteomic analysis to comprehensively identify specific intracellular signaling pathways involved in Y114C-HLCs, and identified the specific proteins changed only in Y114C-HLCs, in comparison with disease control HLCs from ATTR Val30Met amyloidosis (V30M-HLCs). Moreover, we have succeeded in identifying several specific intracellular signals that are significantly activated in Y114C-HLCs, including cellular responses to stress and extracellular matrix organization. Our proteomic analysis is the first to report that the specific point mutations in ATTRv amyloidosis cause dynamic changes in cellular response, and reveal the specific intracellular signals may be involved in the specific pathogenesis of ATTR Tyr114Cys amyloidosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102012"},"PeriodicalIF":2.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}