Biochemical and biophysical research communications最新文献

{"title":"Dual knockout of Fas and TCRα in Jurkat reporter cells enables highly sensitive identification of antigen-specific TCRs","authors":"Yujia Sun ,&nbsp;Ayako Demachi-Okamura ,&nbsp;Shuichi Shinohara ,&nbsp;Yizheng Wang ,&nbsp;Zhongliang Guo ,&nbsp;Rui Yamaguchi ,&nbsp;Hirokazu Matsushita ,&nbsp;Tsukasa Nabekura ,&nbsp;Daisuke Muraoka","doi":"10.1016/j.bbrc.2026.153400","DOIUrl":"10.1016/j.bbrc.2026.153400","url":null,"abstract":"<div><div>T-cell receptors (TCRs) that target tumor antigens are crucial for antitumor immunity; however, tumor-specific TCRs often exhibit low affinity for their cognate antigens, making the identification of functional TCRs challenging due to the limited sensitivity of current detection methods. In this study, we established a high-sensitivity TCR screening platform by generating Jurkat cell reporter clones with dual knockout (DKO) of endogenous Fas and TCRα via CRISPR–Cas9 system. In a viral antigen model system, these DKO Jurkat cells exhibited approximately 100-fold greater sensitivity to antigen stimulation compared with parental Jurkat cells. Notably, our DKO Jurkat–based platform enabled the identification of tumor-specific CD8⁺ T cells from a lung cancer patient that could not be detected using parental Jurkat cells. Moreover, the identified tumor-specific T-cell clone exhibited a unique phenotype characterized by robust cytotoxic T lymphocyte (CTL) activity and natural killer–like properties. Together, these findings demonstrate that dual deletion of Fas and TCRα in Jurkat cells enables highly sensitive functional TCR screening. Integration of this platform with single-cell analysis facilitates the discovery of previously uncharacterized tumor-reactive TCRs and provides a powerful tool for advancing TCR-based cancer immunotherapy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153400"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137103","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":"Targeted introduction of T cell receptor genes at the TRAC locus in cytotoxic T lymphocytes regenerated from human iPSCs by genome editing","authors":"Dil Afroza ,&nbsp;Koji Terada ,&nbsp;Koyu Ito ,&nbsp;Md. Abdul Jabbar Khan ,&nbsp;Kenta Kondo ,&nbsp;Kana Yamasaki ,&nbsp;Seiji Nagano ,&nbsp;Kyoko Masuda ,&nbsp;Hiroshi Kawamoto ,&nbsp;Yasutoshi Agata","doi":"10.1016/j.bbrc.2026.153623","DOIUrl":"10.1016/j.bbrc.2026.153623","url":null,"abstract":"<div><div>Cytotoxic T lymphocytes (CTLs) regenerated from induced pluripotent stem cells (iPSCs) have emerged as an ideal cellular material for introduction of T-cell receptor (TCR) genes specific for defined tumor antigens, as they can be expanded virtually indefinitely while retaining potent cytolytic activity. Indeed, we previously demonstrated that introducing tumor antigen-specific TCR genes into iPSC-derived CTLs using retroviral or lentiviral vectors confers effective antitumor activity. Nonetheless, viral vector-mediated transfer results in random, multicopy genomic integration, which may yield heterogeneous TCR expression and oncogenic transformation depending on the insertion site. In this study we thus attempted to introduce distinct tumor antigen-specific TCR genes into the endogenous T-cell receptor α constant (TRAC) locus of iPSC-derived CTLs by genome editing. The engineered CTLs displayed robust antigen-specific expansion enabled by stable expression of the introduced TCRs under native regulatory control. Moreover, they produced IFN-γ and upregulated the degranulation marker CD107a in an antigen-specific manner, and exhibited strong cytotoxic activity against target cells expressing the cognate peptide. Collectively, these results provide the first demonstration, to our knowledge, that successful TCR replacement was achieved in iPSC-derived CTLs via genome editing and that the introduced TCRs are functionally competent.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"813 ","pages":"Article 153623"},"PeriodicalIF":2.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484428","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":"Exposure to hexavalent chromium and 1800 MHz electromagnetic radiation can synergistically induce intracellular DNA damage in mouse embryonic fibroblasts","authors":"Ying Zhu ,&nbsp;Longtao Zhu ,&nbsp;Yue Lan ,&nbsp;Chuan Sun ,&nbsp;Guangdi Chen","doi":"10.1016/j.bbrc.2026.153360","DOIUrl":"10.1016/j.bbrc.2026.153360","url":null,"abstract":"<div><div>Radiofrequency electromagnetic fields (RF-EMF) are widely present in the modern environment and have been classified by the International Agency for Research on Cancer as possibly carcinogenic to humans (Group 2B). However, their potential role as co-carcinogens remains unclear. The present study aimed to evaluate whether 1800 MHz RF-EMF exposure can modulate chemically induced DNA damage. Mouse embryonic fibroblasts (MEF) were exposed to RF-EMF alone or in combination with hydrogen peroxide (H₂O₂), 4-nitroquinoline-1-oxide (4NQO), cadmium (Cd²⁺), or hexavalent chromium [Cr(VI)]. RF-EMF exposure was performed using a waveguide system under standardized, non-thermal conditions, and DNA damage was assessed using the alkaline comet assay. RF-EMF exposure alone did not induce detectable DNA damage, nor did it significantly enhance DNA damage caused by H₂O₂, 4NQO, or Cd²⁺. In contrast, co-exposure to RF-EMF and Cr(VI) resulted in a significant synergistic increase in DNA damage in MEF cells. These findings suggest that RF-EMF may selectively exacerbate Cr(VI)-induced genotoxicity, highlighting the need for further investigation into the underlying co-toxic mechanisms.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153360"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077012","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":"Multistep molecular trajectory of monocytic myeloid-derived suppressor cell induction by diffuse large B-cell lymphoma cells","authors":"Yu Inoue ,&nbsp;Yuji Shimura ,&nbsp;Yui Niiyama-Uchibori ,&nbsp;Shotaro Chinen ,&nbsp;Takahisa Nakamura ,&nbsp;Haruya Okamoto ,&nbsp;Takahiro Fujino ,&nbsp;Taku Tsukamoto ,&nbsp;Shinsuke Mizutani ,&nbsp;Junya Kuroda","doi":"10.1016/j.bbrc.2026.153287","DOIUrl":"10.1016/j.bbrc.2026.153287","url":null,"abstract":"<div><div>This study aimed to investigate how tumor cells from diffuse large B-cell lymphoma (DLBCL) induce monocytic myeloid-derived suppressor cells (M-MDSCs) from normal peripheral blood mononuclear cells (PBMCs), using an indirect co-culture system that involves normal PBMCs and four human DLBCL -derived cell lines (HDBCLs). All four HDBCLs secreted macrophage migration inhibitory factor (MIF), and two HDBCLs with a stronger ability to induce M-MDSCs also secreted interleukin-10 (IL-10). We revealed that MIF plays a crucial but preparatory role in M-MDSC induction, as its inhibition strongly suppressed M-MDSC formation, whereas recombinant MIF alone exhibited only minimal inductive activity. In contrast, neutralizing IL-10 in IL-10-secreting HDBCLs suppressed M-MDSC induction, whereas adding recombinant IL-10 to IL-10-non-secreting HDBCLs enhanced it, indicating that IL-10 has a more facilitative role. Gene sets associated with the inflammatory response and tumor necrosis factor-α signaling, along with inflammatory molecules, such as IL-1α, were upregulated in the CD33⁺ myeloid fraction of PBMCs at 24 h, before decreasing at 96 h, in co-cultures with HDBCLs that do not secrete IL-10. Furthermore, recombinant IL-10 further downregulated these inflammatory signals while enhancing M-MDSC induction. This indicates that the multistep molecular process of M-MDSC induction from PBMCs by the co-presence of HDBCLs begins with a transient early hyper-inflammatory phase and transitions into a post-inflammatory immunosuppressive phase. Our study demonstrates that treatments that target specific molecular phases regulated by cytokines could reduce M-MDSC induction and improve the effectiveness of immune cell therapy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153287"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071121","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":"Gut microbiota modulates the effects of host-derived fecal microRNAs on cultured gut microbiota in mice","authors":"Ayumi Shijo ,&nbsp;Fumina Ohsaka ,&nbsp;Kei Sonoyama","doi":"10.1016/j.bbrc.2026.153378","DOIUrl":"10.1016/j.bbrc.2026.153378","url":null,"abstract":"<div><div>We previously reported that murine fecal microRNAs (miRNAs) alter the composition of cultured gut microbiota and selectively increase <em>Enterococcus</em>. Since host miRNA expression is influenced by microbial colonization, this study investigated whether fecal miRNAs derived from germ-free (GF) and specific pathogen-free (SPF) mice differentially affect the composition and metabolic activity of cultured gut microbiota. Fecal miRNAs isolated from GF and SPF mice were added to cultures of murine gut microbiota. 16S rRNA gene sequencing showed that GF mice- and SPF mice-derived miRNAs altered microbial community structures in distinct ways. ANCOM identified <em>Enterococcus</em> as the only taxon significantly increased by miRNA treatment. GF mice-derived miRNAs significantly enhanced fermentation, as evidenced by a lower culture pH and higher concentrations of acetate, propionate, and lactate compared with SPF mice-derived miRNAs or vehicle controls. Correlation analysis demonstrated positive associations between organic acid levels and secondary fermenters, including <em>Alloprevotella</em>, <em>Muribaculum</em>, <em>Lachnoclostridium</em>, and Peptococcaceae. In contrast, typical saccharolytic butyrate producers such as <em>Blautia</em>, Lachnospiraceae, and Oscillospiraceae showed negative correlations. Microarray analysis revealed differences in the fecal miRNA profiles of GF and SPF mice, supporting the hypothesis that microbial exposure modulates fecal miRNA composition. Fecal miRNAs derived from antibiotic-treated mice did not reproduce the broad fermentation-promoting effects observed with GF mice-derived miRNAs, although lactate concentration increased. These observations suggest that fecal miRNAs promote fermentation by stimulating <em>Enterococcus</em> and downstream cross-feeding networks, and that prior microbial exposure attenuates this effect. Consequently, fecal miRNAs appear to represent a coevolved host mechanism that modulates microbial fermentation to maintain intestinal homeostasis.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153378"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103323","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":"Argininosuccinate lyase from Escherichia coli as a novel DNA-binding protein","authors":"Jiwoun Park ,&nbsp;Jimin Min ,&nbsp;Jaeho Jeong ,&nbsp;Che-Hun Jung","doi":"10.1016/j.bbrc.2026.153376","DOIUrl":"10.1016/j.bbrc.2026.153376","url":null,"abstract":"<div><div>Metabolic enzymes are increasingly recognized to perform functions beyond their canonical roles. Here, we report that <em>Escherichia coli</em> argininosuccinate lyase (ArgH), a central enzyme in arginine biosynthesis, directly binds duplex DNA <em>in vitro</em>. This study was prompted by reproducible observations of a nucleic acid-like component while isolating ArgH by anion-exchange chromatography. To characterize ArgH-DNA interactions, six duplex DNAs were selected based on structure-guided docking simulations (PADA1 and HDOCK), and their dissociation constants (<em>K</em>_<em>D</em>) were determined by fluorescence spectroscopy. The <em>K</em>_<em>D</em> values ranged from 60 to 200 nM, suggesting that the duplex DNAs interacted with ArgH strongly. These observations suggested ArgH as a previously unrecognized DNA-binding protein and provided a quantitative basis for exploring additional roles of this metabolic enzyme in nucleic acid-associated cellular processes.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153376"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112162","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":"Structural basis of LY334370 recognition and selectivity at the 5-HT1F receptor","authors":"Yumeng Wang ,&nbsp;Chunyu Wang ,&nbsp;Can Cao","doi":"10.1016/j.bbrc.2026.153313","DOIUrl":"10.1016/j.bbrc.2026.153313","url":null,"abstract":"<div><div>The 5-HT_1F receptor is a serotonin receptor subtype highly expressed in trigeminal sensory neurons, where it modulates neuropeptide release and nociceptive signaling without inducing vasoconstriction. This makes it an important therapeutic target for migraine. LY334370 was developed as a first-generation selective 5-HT_1FR agonist and demonstrated efficacy in clinical studies. However, the molecular mechanism underlying 5-HT_1FR activation by LY334370 remains poorly understood. Here, we determined a 3.13 Å cryo-EM structure of the LY334370-bound 5-HT_1FR-miniGα_oA complex. Combined with functional analyses, this structure delineates the molecular determinants underlying LY334370 recognition. Comparison with BRL54443 indicates that LY334370 selectivity for 5-HT_1FR is driven by its optimal accommodation within the receptor-specific extended binding pocket. Furthermore, comparative analysis with the lasmiditan-bound 5-HT_1FR-Gα_i1 complex reveals distinct agonist binding modes and provides mechanistic insight into Gα_i/o subtype-specific coupling. Collectively, these findings elucidate the structural basis of 5-HT_1FR activation, ligand selectivity, and G protein coupling, providing a structural framework for the rational design of safer and more effective anti-migraine drugs.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153313"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077009","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":"Erianin induces ferroptosis in ovarian cancer cells by upregulating PDP2 and activating the JNK signaling pathway","authors":"Chaoyan Fan,&nbsp;Min Peng,&nbsp;Wuguang Zhang","doi":"10.1016/j.bbrc.2026.153353","DOIUrl":"10.1016/j.bbrc.2026.153353","url":null,"abstract":"<div><h3>Purpose</h3><div>Ovarian cancer remains the deadliest gynecologic malignancy. Erianin, a plant-derived compound with antitumor activity through inducing ferroptosis—an iron-dependent programmed cell death that has been shown in other contexts to enhance tumor sensitivity to chemotherapy—has not yet been fully explored in ovarian cancer. We therefore evaluated its anti-proliferative effects and underlying mechanism.</div></div><div><h3>Methods</h3><div>Cell viability (CCK-8), cell death (Annexin V-FITC/PI flow cytometry, Western blot), and lipid peroxidation assays were performed in A2780 and ES-2 cells. Transcriptome (RNA-seq) and GO enrichment analyses identified signaling pathways, followed by mechanistic validation. Antitumor efficacy was verified in a nude-mouse xenograft model.</div></div><div><h3>Results</h3><div>Erianin exhibited a dose-dependent inhibitory effect on the proliferation of ovarian cancer cells A2780 and ES-2. Ferroptosis was identified as the primary mode of cell death, supported by a combination of evidence: (i) preferential rescue with the ferroptosis inhibitor Ferrostatin-1; (ii) characteristic molecular changes, including downregulation of key suppressors (GPX4, FTH1, SLC7A11) and upregulation of the pro-ferroptotic protein ACSL4; and (iii) elevated lipid peroxidation (MDA) and ROS alongside depleted GSH. Annexin V-FITC/PI flow cytometry was used to assess overall cell death patterns. Mechanistic studies showed that Erianin promoted ferroptosis via activation of the JNK signaling pathway and upregulation of PDP2 expression. In vivo, Erianin significantly suppressed tumor growth and induced molecular changes indicative of a less aggressive phenotype, including modulation of epithelial-mesenchymal transition (EMT) markers (increased E-cadherin, decreased N-cadherin).</div></div><div><h3>Conclusion</h3><div>Erianin induces ferroptosis via PDP2-mediated activation of the JNK signaling pathway, thereby restraining ovarian cancer growth in vitro and in vivo. These findings provide a mechanistic rationale for further evaluation of Erianin as a ferroptosis-inducing therapeutic candidate, including in chemoresistant settings.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153353"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077011","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":"Unraveling the miRNA–EMT–stemness interplay in fusion-positive supratentorial ependymomas: Identifying therapeutic vulnerabilities","authors":"Agrima Sharma ,&nbsp;Ritu Kulshreshtha ,&nbsp;Shyam S. Chauhan ,&nbsp;Rafat Malik ,&nbsp;Vaishali Suri ,&nbsp;Amandeep Jagdevan ,&nbsp;Mehar Chand Sharma","doi":"10.1016/j.bbrc.2026.153349","DOIUrl":"10.1016/j.bbrc.2026.153349","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Supratentorial ependymomas frequently harbor &lt;em&gt;ZFTA-RELA (ZR&lt;/em&gt;fus) gene fusions that initiate oncogenic transcriptional programs; however, the downstream post-transcriptional regulatory mechanisms remain poorly understood. This study aimed to elucidate the contribution of microRNAs (miRNAs) to the aggressive phenotype characteristic of &lt;em&gt;ZR&lt;/em&gt;fus &lt;sup&gt;+&lt;/sup&gt; tumors.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Small RNA sequencing was performed on fusion-positive (&lt;em&gt;ZR&lt;/em&gt;fus&lt;sup&gt;+&lt;/sup&gt;) and fusion-negative (&lt;em&gt;ZR&lt;/em&gt;fus&lt;sup&gt;−&lt;/sup&gt;) supratentorial ependymomas, followed by integrative bioinformatic analyses. Differentially expressed miRNAs and their predicted mRNA targets were validated using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Associations with clinical outcomes were evaluated through progression-free survival (PFS) analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Distinct miRNA expression profiles discriminated &lt;em&gt;ZR&lt;/em&gt;fus&lt;sup&gt;+&lt;/sup&gt; from &lt;em&gt;ZR&lt;/em&gt;fus&lt;sup&gt;−&lt;/sup&gt; tumors. &lt;em&gt;ZR&lt;/em&gt;fus &lt;sup&gt;+&lt;/sup&gt; tumors demonstrated significant upregulation of hsa-miR-138-5p and downregulation of hsa-miR-135b-5p and hsa-miR-216a-3p. Target prediction and pathway enrichment analyses identified TERT, YAP1, RELA, and TP53 as key dysregulated network nodes. Functionally, ZRfus&lt;sup&gt;+&lt;/sup&gt; tumors exhibited enhanced epithelial–mesenchymal transition (EMT) and stemness signatures, marked by upregulation of SNAIL, SLUG, Nestin, and N-Cadherin. Clinically, &lt;em&gt;ZR&lt;/em&gt;fus &lt;sup&gt;+&lt;/sup&gt; status correlated with significantly shorter progression-free survival, underscoring its adverse prognostic significance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study delineates a distinct &lt;em&gt;ZR&lt;/em&gt; fus-associated miRNA landscape in supratentorial ependymomas, implicates hsa-miR-138-5p as a potential biomarker of oncogenic signaling and EMT activation, and reveals mechanistic links between fusion-driven transcriptional dysregulation and tumor aggressiveness. These findings lay the groundwork for miRNA-based therapeutic strategies in high-risk pediatric ependymoma subtypes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Importance of the study&lt;/h3&gt;&lt;div&gt;Supratentorial ependymomas with &lt;em&gt;ZFTA–RELA&lt;/em&gt; fusions represent a highly aggressive pediatric brain tumor subtype, yet the post-transcriptional mechanisms driving their malignancy remain unclear. This study fills a critical gap by systematically profiling miRNA expression in fusion-positive and fusion-negative supratentorial ependymomas, revealing a distinct fusion-associated miRNA signature. The identification of hsa-miR-138-5p upregulation and hsa-miR-135b-5p/hsa-miR-216a-3p downregulation, converging on key oncogenic nodes such as TERT, YAP1, RELA, and TP53, provides novel mechanistic insight into how fusion-driven miRNA dysregulation enhances epithelial–mesenchymal transition and stemness. The findings suggest that miRNA–fusion interactions play an important role in tumor aggre","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153349"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103456","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":"Mitochondrial dysfunction in MASH: Focusing on chronic inflammation and intercellular communication","authors":"Wanyi Luo ,&nbsp;Muxin Yu ,&nbsp;Chuwei Zheng ,&nbsp;Xiaowen Li ,&nbsp;Xiaotian Ma ,&nbsp;Guocheng Zeng ,&nbsp;Jinming Zhang ,&nbsp;Xia Ji ,&nbsp;Liyan Sun","doi":"10.1016/j.bbrc.2026.153356","DOIUrl":"10.1016/j.bbrc.2026.153356","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition closely linked to metabolic dysregulation. In its progressive stage, metabolic dysfunction-associated steatohepatitis (MASH), hepatocytes face pathological insults including lipotoxicity and inflammatory cell infiltration. Sustained exposure to these stressors severely disrupts hepatocyte mitochondrial homeostasis, culminating in mitochondrial dysfunction. Crucially, mitochondrial dysfunction is intimately associated with chronic inflammation. After injury, mitochondria produce large amounts of mitochondrial reactive oxygen species (mtROS) or release mitochondrial damage-associated molecules that act as signaling molecules to recruit and activate inflammatory cells, such as neutrophils. Activated neutrophils release neutrophil extracellular traps (NETs), which exacerbate liver inflammation, driving MASH progression towards liver cancer. Despite advances in the understanding of MASLD pathophysiology, challenges remain in identifying relation between mitochondrial dysfunction and intrahepatic inflammation. Intercellular communication, primarily mediated by extracellular vesicles (EVs), plays a pivotal role in this pathology. EVs transport diverse bioactive cargo from donor to recipient cells, modulating various pathophysiological processes. This review synthesizes current literature on mitochondrial dysfunction and chronic inflammation in MASH/MASLD, examines the critical role of intrahepatic intercellular communication, particularly via EVs, and highlights targeting mitochondria as a promising therapeutic strategy for MASH.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"Article 153356"},"PeriodicalIF":2.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076943","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}