Biochimica et biophysica acta. General subjects最新文献

{"title":"The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center","authors":"Takumi Baba ,&nbsp;Go Ueno ,&nbsp;Chika Ohe ,&nbsp;Shuku Saji ,&nbsp;Sachiko Yamamoto ,&nbsp;Masaki Yamamoto ,&nbsp;Hiroshi Nakagawa ,&nbsp;Nobuo Okazaki ,&nbsp;Mamoru Ouchida ,&nbsp;Iori Kawasaki Ohmori ,&nbsp;Kohei Takeshita","doi":"10.1016/j.bbagen.2025.130860","DOIUrl":"10.1016/j.bbagen.2025.130860","url":null,"abstract":"<div><div>Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in <em>Txn</em>-F54L mutant rats; however, the details of why the <em>Txn</em> mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the <em>Txn</em>-F54L rats.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130860"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a polyclonal antibody against the protein encoded by the metabolic syndrome-associated gene for dissecting its function and underlying mechanism","authors":"Jia Jing Cai ,&nbsp;Yi Lin Shen ,&nbsp;Jia Lin ,&nbsp;Jun Tao Ren ,&nbsp;Yan Zhi Yi ,&nbsp;Xue Cheng Li ,&nbsp;Ke Xin Jia ,&nbsp;Jun Yi Liu ,&nbsp;Guo Ming Su ,&nbsp;Yong Yan Song ,&nbsp;Qi Wei Guo ,&nbsp;Ding Zhi Fang","doi":"10.1016/j.bbagen.2025.130870","DOIUrl":"10.1016/j.bbagen.2025.130870","url":null,"abstract":"<div><div>The metabolic syndrome-associated gene (<em>MSAG</em>) encodes a polypeptide of MSAG composed of 110 amino acids and was observed to responds to high glucose conditions. However, scant studies have been documented since it was first reported in 2009. The function of MSAG and its underlying mechanisms remain unclear. To explore them, antibodies against MSAG are needed. Therefore, the current study aimed to generate a polyclonal antibody against MSAG and assess its applications. The pET-28a-m<em>MSAG</em> vector was constructed for prokaryotic expression. The recombinant MSAG was obtained and identified with a coverage of 100 %. Subsequently, a polyclonal antibody against MSAG was prepared by rabbit immunization with an antibody titer exceeding 1:128,000 as determined by ELISA. The prepared antibody was validated using <em>MSAG</em> knockdown mouse and HepG2 cells. The mRNA and protein levels of <em>MSAG</em> were lower in <em>MSAG</em> knockdown mouse livers and HepG2 cells. Additionally, <em>MSAG</em> mRNA and protein levels in mouse hepatic tissues were significantly increased following the intervention with a high carbohydrate diet as evaluated by RT-qPCR and western blotting using the prepared antibody. This reproducibly demonstrated that MSAG was involved in the regulation of glucose metabolism. Taken together, the rabbit anti-MSAG polyclonal antibody has been successfully generated in the current study, which lays the foundation for future studies to explore the functions of MSAG and its underlying mechanisms.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130870"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhipicephalus microplus triosephosphate isomerase dimer interface is stabilized by a key cysteine residue","authors":"Luiz Saramago ,&nbsp;Nallely Cabrera ,&nbsp;Beatriz Aguirre ,&nbsp;Helga Gomes ,&nbsp;Bruno Moraes ,&nbsp;Valdir Braz ,&nbsp;Itabajara da Silva Vaz Jr. ,&nbsp;Mayra A. Marques ,&nbsp;Jerson L. Silva ,&nbsp;Tomohiro Okagawa ,&nbsp;Satoru Konnai ,&nbsp;Ruy Pérez-Montfort ,&nbsp;Carlos Logullo ,&nbsp;Jorge Moraes","doi":"10.1016/j.bbagen.2025.130857","DOIUrl":"10.1016/j.bbagen.2025.130857","url":null,"abstract":"<div><div>The functional significance of a non-conserved cysteine residue (C86) proximal to the interfacial region of <em>Rhipicephalus microplus</em> triosephosphate isomerase (RmTIM) was investigated through systematic substitution with aspartic acid (C86D), lysine (C86K), and alanine (C86A) via site-directed mutagenesis. Kinetic analyses revealed substantial perturbations in enzymatic parameters for the C86D and C86K variants, with marked alterations in maximal velocity (<em>V</em>_max), substrate affinity (<em>K</em>_m), catalytic turnover (<em>k</em>_cat), and catalytic efficiency (<em>k</em>_cat/<em>K</em>_m). Thermodynamic destabilization was universally observed across all mutants via Protein Thermal Shift assays, with reductions in melting temperature (<em>T</em>_m) ranging from 15.7 to 27.1 °C relative to the wild-type enzyme (Wt-TIM). Chemical denaturation studies employing guanidine hydrochloride demonstrated heightened susceptibility to unfolding in all mutants, with destabilization profiles following the order: C86K &gt; C86D &gt; C86A. Computational structural analyses elucidated molecular mechanisms underlying these perturbations. Disruption of a putative salt bridge between residues D49 and K18 was predicted in the C86K mutant, potentially destabilizing the dimeric interface. Comparative free energy calculations (ΔG) further corroborated these findings: Wt-TIM exhibited a ΔG of −21.2 kcal/mol and an interfacial contact area of 1604.8 Å², indicative of robust dimeric stabilization. In contrast, the C86K mutant displayed diminished stability (ΔG = −16.0 kcal/mol) despite an expanded interface (1615.6 Å²), suggesting compromised packing efficiency. These observations imply that C86, while not directly conserved, plays a critical structural role in maintaining interfacial integrity and catalytic competence. The pronounced destabilization and kinetic impairment observed in the C86K variant highlight the residue's significance in RmTIM functionality. This residue-specific destabilization strategy may aid in the rational design of acaricidal compounds targeting interfacial regions of RmTIM, taking advantage of structural vulnerabilities produced by non-conserved residues.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130857"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid kinase activity detection and kinetic analysis using a convenient EGFR FRET-based detection probe","authors":"Kittitat Jaengwang ,&nbsp;Suleeporn Pommayon ,&nbsp;Chanikan Sonklin ,&nbsp;Kiattawee Choowongkomon ,&nbsp;Dujdaun Waraho-Zhmayev ,&nbsp;Lueacha Tabtimmai","doi":"10.1016/j.bbagen.2025.130854","DOIUrl":"10.1016/j.bbagen.2025.130854","url":null,"abstract":"<div><div>In modern drug discovery, there is a pressing need for rapid, cost-effective, and accessible methods to evaluate the biological activities of newly synthesized compounds. Traditional kinase assay platforms are often labor-intensive, time-consuming, and require specialized equipment or expertise. To address these limitations, we developed and validated a convenient in vitro kinase assay based on a recombinant biosensor, Picchu-B, constructed using a bacterial expression system. Picchu-B, derived from the live-cell EGFR FRET biosensor Picchu, was successfully expressed as a highly soluble, fluorescent protein. It served as a direct Probe for EGFR kinase, enabling real-time FRET-based detection of kinase activity. Optimization of Picchu-B concentration revealed a linear correlation between FRET signal intensity and EGFR-TK levels. The biosensor demonstrated high selectivity for EGFR and its clinically relevant mutants (e.g., T790M/L858R), with minimal cross-reactivity to unrelated kinases such as JAK-2. Enzyme kinetic studies confirmed nucleotide specificity of EGFR-TK in the presence of Picchu-B. This study highlights Picchu-B as a practical and scalable tool for EGFR-targeted drug screening, offering significant advantages in speed, and simplicity over conventional approaches.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130854"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK regulates BK-channel current in CA1 hippocampal neurons","authors":"Ricardo Esquivel-Garcia,&nbsp;Jorge Bravo-Martinez,&nbsp;Karina Bermeo,&nbsp;Isabel Arenas,&nbsp;David E. Garcia","doi":"10.1016/j.bbagen.2025.130862","DOIUrl":"10.1016/j.bbagen.2025.130862","url":null,"abstract":"<div><div>AMP-activated protein kinase (AMPK) is a fundamental energy sensor fine-tuning cellular activity based on ATP availability. On the other hand, BK-channel current is tightly regulated by leptin, which in turn regulates neuronal excitability by modulating ion channels such as the BK-channel. However, this mechanism remains unclear to date. In this work we aimed to determine whether AMPK mediates the leptin regulation on BK-channel. We hypothesized that leptin regulation of BK-channel through AMPK underlies the modulating changes in neuronal excitability of CA1 hippocampal neurons. By using patch-clamping methods on CA1 pyramidal neurons in brain slices and biochemical reagents, we found that AMPK activation with AICAR inhibits BK-channel current, while AMPK inhibition with Compound C enhances BK-channel activity. Remarkably, AMPK activation reverses BK-channel current enhanced by leptin supporting an AMPK-dependent metabolic regulation of BK. Accordingly, current-clamp experiments revealed that AMPK manipulations significantly affect leptin responses on CA1 neuronal firing. These results support AMPK as a key mediator of the interplay between leptin and neuronal excitability, readily integrating metabolic signals with the computing state of firing outputs in CA1 hippocampal neurons.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130862"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in the transcriptome of human primary bronchial epithelial cells exposed to emissions from a heated tobacco product","authors":"M. Davigo ,&nbsp;F. Caiment ,&nbsp;M. Verheijen ,&nbsp;F.J. van Schooten ,&nbsp;M. van Herwijnen ,&nbsp;A. Mommers ,&nbsp;A. Opperhuizen ,&nbsp;R. Talhout ,&nbsp;A.H.V. Remels","doi":"10.1016/j.bbagen.2025.130869","DOIUrl":"10.1016/j.bbagen.2025.130869","url":null,"abstract":"<div><h3>Introduction</h3><div>IQOS is a Heated Tobacco Product marketed as reduced-risk alternative to cigarettes. This is based on limited industry-independent toxicological evidence.</div></div><div><h3>Methods</h3><div>Cigarette Smoke Extract (CSE) and IQOS extract (IQOSE) were generated by puffing mainstream emissions in PBS. Nicotine levels were quantified <em>via</em> liquid chromatography-mass spectrometry (LC-MS). Subsequently, undifferentiated Primary human Bronchial Epithelial Cells (PBECs) from three donors were exposed (24 h) to 1 %CSE, 1 %IQOSE, 3 %IQOSE (<em>v</em>/v), or nicotine concentrations (1.5, 6 or 18 μg/mL), representative of the levels present in the extracts. Transcriptomic alterations were assessed <em>via</em> RNA sequencing, and specific mRNA alterations were validated at the protein level by Western blot.</div></div><div><h3>Results</h3><div>IQOSE contained about 4-fold more nicotine than CSE. Nicotine did not significantly affect PBECs transcriptome. Substantial differences in the amount of differentially expressed genes (DEGs) were observed in response to CSE and IQOSE between donors. However, in all donors, 3 %IQOSE exposure downregulated pathways involved in cell cycle progress. In addition, both mRNA and protein levels of molecules controlling autophagy and mitophagy increased in response to IQOSE in one donor, and the disease Chronic Obstructive Pulmonary Disease (COPD) was enriched in cells from two donors upon exposure to CSE or IQOSE. In the most responsive donor, pathways associated with ER-stress and DNA replication were deregulated.</div></div><div><h3>Conclusions</h3><div>Despite significant inter-donor variability, IQOSE induced specific gene signatures associated with pathways known to be involved in (smoking-related) lung diseases in all donors. Collectively, these findings provide novel insights into the molecular toxicity of IQOS mainstream emissions in human bronchial epithelial cells.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130869"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for singlet oxygen production from indocyanine green by electron paramagnetic resonance","authors":"Magdalena Szpunar ,&nbsp;David Aebisher ,&nbsp;Bogumił Cieniek ,&nbsp;Ireneusz Stefaniuk ,&nbsp;Łukasz Dubiel ,&nbsp;Andrzej Wal","doi":"10.1016/j.bbagen.2025.130861","DOIUrl":"10.1016/j.bbagen.2025.130861","url":null,"abstract":"<div><div>Indocyanine green (ICG) is a well-known dye used for cardiovascular fluorescence imaging in medicine and a potential photosensitizer for photodynamic therapy. Using electron paramagnetic resonance (EPR), we have shown that illumination of aqueous solutions of ICG leads to the generation of singlet oxygen. The use of a selective spin trap allowed for the rate of singlet oxygen generation to be determined which provides evidence that ICG undergoes Type II photosensitization.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130861"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ-ATF7IP promotes IL13RA1 dependent M2 polarization of macrophage via sponging MiR-488-3p in papillary thyroid carcinoma","authors":"Yan Hu ,&nbsp;Shujun Xia ,&nbsp;Yanhua Yang ,&nbsp;Weiwei Zhan","doi":"10.1016/j.bbagen.2025.130855","DOIUrl":"10.1016/j.bbagen.2025.130855","url":null,"abstract":"<div><div>The preoperative assessment of lymph node metastasis (LNM) is of critical importance for the selection of appropriate surgical and therapeutic strategies for papillary thyroid carcinoma (PTC). However, the mechanisms underlying LNM in PTC remain unclear, and effective diagnostic tools are currently lacking. This study aims to identify circRNAs as diagnostic molecular markers for LNM and to investigate their molecular mechanisms in the occurrence of LNM in PTC. In this study, bioinformatics analysis and qPCR verification were used and identified that circ-ATF7IP was the key molecule in PTC progression and overexpressed in PTC patients with LNM. Mechanistically, circ-ATF7IP acts as a molecular sponge for miR-488-3p in PTC cells. PTC cell-derived miR-488-3p acts on macrophage (Mɸ) through exosome transfer. In Mɸ, miR-488-3p negatively regulates IL13RA1 at post transcription stage, facilitating M2 phenotype polarization. This reshapes the tumor microenvironment, enhancing tumor invasiveness. To be brief, circ-ATF7IP is a newly identified biomarker for PTC related LNM. Targeting circ-ATF7IP/miR-488-3p/IL13RA1 axis is a promising therapeutic strategy for PTC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130855"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X7 receptor contributes to DNA damage repair and acquisition of malignant phenotypes in irradiated human glioblastoma cells","authors":"Hiromu Seki ,&nbsp;Kazuki Kitabatake ,&nbsp;Fumiaki Uchiumi ,&nbsp;Sei-ichi Tanuma ,&nbsp;Mitsutoshi Tsukimoto","doi":"10.1016/j.bbagen.2025.130873","DOIUrl":"10.1016/j.bbagen.2025.130873","url":null,"abstract":"<div><div>Radiation therapy for cancer takes advantage of the higher sensitivity of tumor cells to radiation compared to normal tissue, but some cancers, such as glioblastoma (GBM) and malignant melanoma, acquire radiation resistance (radioresistance), rendering treatment ineffective. Radioresistance is characterized by strong activation of DNA repair mechanisms in response DNA damage induced by radiation, together with possession of malignant property such as enhanced invasiveness and metastasis, though the molecular mechanisms involved remain to be fully established. Here, we show that P2X7 receptor-specific inhibitors suppress the γ-irradiation-induced DNA damage response (DDR) and enhance cell death of A172 GBM cells. In contrast, ATP, a P2X7 receptor ligand, promotes the DDR and suppresses cell death. Irradiation immediately induced ATP release from cells, and P2X7 receptor inhibitor suppressed the release of ATP. Furthermore, P2X7 receptor inhibitors suppress the release of high mobility group box 1 (HMGB1), which is known to promote cancer cell migration. Inhibitors of the receptor for advanced glycation end products (RAGE) also suppress ATP-induced cell motility, indicating that the P2X7-HMGB1-RAGE pathway contributes to radiation-induced malignant transformation. These data indicate firstly that the P2X7 receptor promotes the γ-irradiation-induced DDR, leading to increased resistance of GBM cells to γ-radiation-induced death, and secondly that the P2X7 receptor and extracellular ATP may be involved in the γ-irradiation-induced acquisition of malignant property such as cytoskeletal changes and enhanced motility in GBM cells.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130873"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Midkine and TNFSF10 as downstream molecules of type I interferon are involved in the treatment of myelofibrosis","authors":"Yaoyao Chen ,&nbsp;Fanxiang Yin ,&nbsp;Xiaoqian Wang ,&nbsp;Huilin Zhang ,&nbsp;Ping Tang ,&nbsp;Mengjiao Xue ,&nbsp;Nannan Sun ,&nbsp;Jin Li ,&nbsp;Chang Chen ,&nbsp;Bingjie Wang ,&nbsp;Qingxuan Xin ,&nbsp;Juanxia Zhou ,&nbsp;Yingmei Li ,&nbsp;Shuya Wang ,&nbsp;Shaohua Yan ,&nbsp;Jiani Li ,&nbsp;Yunling Zhu ,&nbsp;Bo Qin ,&nbsp;Baohong Yue ,&nbsp;Yong Jiang ,&nbsp;Rongqun Guo","doi":"10.1016/j.bbagen.2025.130863","DOIUrl":"10.1016/j.bbagen.2025.130863","url":null,"abstract":"<div><div>Myelofibrosis (MF), a myeloproliferative neoplasm, remains incurable for most patients. Although some individuals are eligible for allogeneic hematopoietic stem cell transplantation, current therapies generally slow disease progression rather than achieve a cure. In this study, we found that type I interferon (IFN) treatment enhances midkine (MDK) expression, and MDK is involved in the differentiation and maturation of progenitor cells. Notably, MDK treatment drives tumor cells into the cell cycle, thereby increasing the therapeutic effect of busulfan. Furthermore, MDK promotes osteogenic differentiation of mesenchymal stem cells (MSC), contributing to the remodeling of the bone marrow microenvironment. In addition, type I IFN upregulates TNFSF10, leading to tumor cell death through mutual killing.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130863"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205518","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}