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Reduction of cell viability and alteration of genomic DNA methylation by phthalates in a normal human fibroblast (NHF) cell line in vitro 邻苯二甲酸盐对体外正常人成纤维细胞(NHF)细胞系细胞活力的降低和基因组DNA甲基化的改变。
IF 3.3
Biochemistry and Biophysics Reports Pub Date : 2026-09-01 Epub Date: 2026-08-24 DOI: 10.1016/j.bbrep.2026.102755
Warqaa Y. Salih, Fikrat M. Hassan, Majeed A. Sabbah
{"title":"Reduction of cell viability and alteration of genomic DNA methylation by phthalates in a normal human fibroblast (NHF) cell line in vitro","authors":"Warqaa Y. Salih,&nbsp;Fikrat M. Hassan,&nbsp;Majeed A. Sabbah","doi":"10.1016/j.bbrep.2026.102755","DOIUrl":"10.1016/j.bbrep.2026.102755","url":null,"abstract":"<div><div>Phthalates are ubiquitous environmental contaminants widely used as plasticizers in poly vinyl chloride products, and growing evidence implicates them in metabolic activity reduction and epigenetic dysregulation. However, their direct effects on non-transformed human cells remain incompletely characterized. The present <em>in vitro</em> study evaluated the reduction in cell viability and DNA methylation–modulating effects of three widely distributed phthalates, di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isononyl phthalate (DINP), on normal human fibroblast (NHF) cells. Cells were exposed to serial concentrations (31.25–1000 μg/mL) for 72 h, and the viability was assessed by MTT assay, followed by IC<sub>50</sub> determination via nonlinear regression. Global DNA methylation was subsequently quantified at the IC<sub>50</sub> concentration by ELISA-based measurement of 5-methylcytosine (5-mC). All three phthalates produced significant concentration-dependent reductions in cell viability. Constraining the regression plateaus to 100% and 0% viability yielded estimated IC<sub>50</sub> values of 19.2 μg/mL for DEHP, 43.4 μg/mL for DnBP, and 13.1 μg/mL for DINP; as viability fell below 50% at the lowest concentration tested, these values represent extrapolation below the sampled range, their confidence intervals overlap, and no potency ranking is asserted. At fixed high-effect concentrations, DEHP and DINP significantly elevated global 5-mC levels to 189.18% and 159.56% of control, respectively, whereas DnBP induced only a non-significant increase (120.06%). These findings indicate that phthalates compromise both the viability and epigenetic integrity of NHF cells in a congener-specific manner, underscoring their potential contribution to methylation-associated human pathologies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"47 ","pages":"Article 102755"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148824728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanism of FXR signaling: from liver inflammation to hepatocellular carcinoma FXR信号传导的机制:从肝脏炎症到肝细胞癌
IF 3.3
Biochemistry and Biophysics Reports Pub Date : 2026-09-01 Epub Date: 2026-08-26 DOI: 10.1016/j.bbrep.2026.102753
Cheng Qiuluo, Huang Guiqun, Han Xue, Zhu Ying
{"title":"Mechanism of FXR signaling: from liver inflammation to hepatocellular carcinoma","authors":"Cheng Qiuluo,&nbsp;Huang Guiqun,&nbsp;Han Xue,&nbsp;Zhu Ying","doi":"10.1016/j.bbrep.2026.102753","DOIUrl":"10.1016/j.bbrep.2026.102753","url":null,"abstract":"<div><h3>Objective</h3><div>To clarify the core regulatory role and molecular mechanism of farnesoid X receptor (FXR) in the progression from liver inflammation/fibrosis to hepatocellular carcinoma (HCC), and to provide a theoretical basis for targeted prevention and treatment of liver diseases.</div></div><div><h3>Methods</h3><div>A systematic review was performed to integrate FXR's key regulatory mechanisms in bile acid homeostasis, inflammatory signaling, metabolic reprogramming, tumor pathways, and the tumor immune microenvironment. Intervention effects of natural compounds and FXR agonists/antagonists were analyzed for clinical translational potential.</div></div><div><h3>Results</h3><div>FXR acts as a core regulator throughout the inflammation–fibrosis–HCC axis via bidirectional mechanisms. (1) In inflammation/fibrosis, FXR activation upregulates BSEP, FGF15/19, and SHP, inhibits CYP7A1 to maintain bile acid homeostasis, suppresses the TLR4/NF-κB axis and NLRP3 inflammasome, reduces IL-6/TNF-α, and directly inhibits hepatic stellate cell activation and matrix deposition. Agonists like INT-767 block progression from chronic hepatitis to fibrosis/cirrhosis (2) In HCC, FXR dysfunction (e.g., HBx C40-mediated). causes bile acid accumulation, glucose metabolic disorders, and Notch1/STAT3 activation, driving HCC progression. FXR activation inhibits STAT3 phosphorylation, glycolytic enzymes, and Wnt activity. Quercetin and obeticholic acid suppress tumor growth via FXR signaling. (3) Aberrant FXR signaling correlates with immune microenvironment dysregulation and immune escape. FXR agonists reshape the microenvironment and enhance anti-PD-1 efficacy; combined FXR and GPC3 detection improves HCC diagnostic specificity.</div></div><div><h3>Conclusion</h3><div>FXR is a central hub regulating the liver inflammation–fibrosis–HCC axis. FXR-targeting agonists, natural compounds, and combination immunotherapy hold significant translational potential. Further studies are needed to clarify FXR's tissue-specific functions and bidirectional mechanisms, and to develop highly selective modulators for precise liver disease prevention and treatment.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"47 ","pages":"Article 102753"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148854156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimal autofluorescence blocking for reliable immunofluorescence in human ovarian samples: A comparison of 4 blocking kits. 在人卵巢样品中可靠免疫荧光的最佳自身荧光阻断:4种阻断试剂盒的比较。
IF 3.3
Biochemistry and Biophysics Reports Pub Date : 2026-08-24 eCollection Date: 2026-09-01 DOI: 10.1016/j.bbrep.2026.102762
Rebekka Einenkel-Ulrich, Johanna Schlingheider, Cara Maria Färber, Andreas Schallmoser, Nicole Sänger
{"title":"Optimal autofluorescence blocking for reliable immunofluorescence in human ovarian samples: A comparison of 4 blocking kits.","authors":"Rebekka Einenkel-Ulrich, Johanna Schlingheider, Cara Maria Färber, Andreas Schallmoser, Nicole Sänger","doi":"10.1016/j.bbrep.2026.102762","DOIUrl":"10.1016/j.bbrep.2026.102762","url":null,"abstract":"<p><strong>Introduction: </strong>Fertility depends on the complex process of folliculogenesis, yet many aspects of early human follicle development remain unclear. Immunohistofluorescence (IHF) enables detailed analysis of follicular structures and allows quantification. However, it is often affected by tissue autofluorescence. This study compares four commercially available kits to identify the most effective method for reducing autofluorescence and improving IHF accuracy.</p><p><strong>Methods: </strong>Sections of human ovarian tissue were treated according to the staining protocol without antibodies, but with one of four kits reducing autofluorescence to compare their efficacy. Images were taken on the Ti2-E fluorescence microscope in three different fluorescence channels.The kit with the highest reduction in autofluorescence was applied for a strong and a rather subtle staining in order to analyze the signal-to-background ratio (SBR).</p><p><strong>Results: </strong>All tested reagents reduced tissue autofluorescence in all three fluorescence channels. Among the evaluated products, TrueBlack showed the greatest reduction in autofluorescence. When combined with IHF staining, it significantly reduced background fluorescence and improved the SBR. Nevertheless, TrueVIEW and Ready Probes were similarly effective.</p><p><strong>Conclusion: </strong>Autofluorescence in human ovarian tissue can be effectively reduced using commercially available reagents. Among the tested products, TrueBlack showed the highest efficacy with our specific protocol and setup. Given the high demand for research and the rarity of suitable human ovarian samples, sharing these results may support more accurate and reproducible immunofluorescence analyses in future studies.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"47 ","pages":"102762"},"PeriodicalIF":3.3,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Salvianolic acid B mitigates senescence and promotes osteogenesis of senescent bone marrow mesenchymal stem cells via the PI3K/AKT pathway. 丹酚酸B通过PI3K/AKT通路减缓衰老并促进衰老骨髓间充质干细胞成骨。
IF 3.3
Biochemistry and Biophysics Reports Pub Date : 2026-06-04 eCollection Date: 2026-06-01 DOI: 10.1016/j.bbrep.2026.102624
Shaozi Zhong, Dianxuan Wu, Qize Chen, Chun Zeng, Huabin Chen, Jie Huang
{"title":"Salvianolic acid B mitigates senescence and promotes osteogenesis of senescent bone marrow mesenchymal stem cells via the PI3K/AKT pathway.","authors":"Shaozi Zhong, Dianxuan Wu, Qize Chen, Chun Zeng, Huabin Chen, Jie Huang","doi":"10.1016/j.bbrep.2026.102624","DOIUrl":"10.1016/j.bbrep.2026.102624","url":null,"abstract":"<p><p>Senescence is a major contributor to osteoporosis, with progressive bone loss in later life characterizing age-related osteoporosis. The decline in bone marrow mesenchymal stem cells (BMSCs) function, particularly the reduction in osteogenic capacity, plays a central role in this process. Therefore, improving the function of senescent BMSCs could potentially slow the age-related osteoporosis progression. Salvianolic acid B (Sal-B), the most abundant and bioactive water-soluble compound derived from the traditional herb <i>Salvia miltiorrhiza</i> and growing evidence supports its efficacy against osteoporosis. However, the underlying cellular and molecular mechanisms remain unclear. This study aimed to investigate the effects and mechanisms of Sal-B on senescent BMSCs in vitro. Our study show that Sal-B not only promoted osteogenic differentiation but also attenuated cellular senescence in senescent BMSCs. Mechanistically, the PI3K/AKT pathway played a crucial role in mediating these beneficial effects. These findings clarify the biological action and mechanism of Sal-B at the cellular level, providing a theoretical foundation for subsequent in vivo studies.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"102624"},"PeriodicalIF":3.3,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computational identification of putative mRNA-miRNA signatures in chemoresistant and metastatic triple-negative breast cancer. 在化疗耐药和转移性三阴性乳腺癌中推测的mRNA-miRNA特征的计算鉴定。
IF 3.3
Biochemistry and Biophysics Reports Pub Date : 2026-06-04 eCollection Date: 2026-06-01 DOI: 10.1016/j.bbrep.2026.102656
Mahvash Farajzadeh-Dehkordi, Elham Rezvani Boroujeni, Sina Darzi, Manijeh Jalilvand, Babak Rahmani
{"title":"Computational identification of putative mRNA-miRNA signatures in chemoresistant and metastatic triple-negative breast cancer.","authors":"Mahvash Farajzadeh-Dehkordi, Elham Rezvani Boroujeni, Sina Darzi, Manijeh Jalilvand, Babak Rahmani","doi":"10.1016/j.bbrep.2026.102656","DOIUrl":"10.1016/j.bbrep.2026.102656","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a heterogeneous malignancy that is recognized as having a high rate of metastasis and limited treatment options. Identifying new molecular signatures for TNBC remains urgent and challenging. In this study, we aimed to identify novel mRNA and miRNA expression profiles associated with invasive and drug-resistant TNBC using bioinformatics methods. We analyzed four datasets (GSE43502, GSE88847, GSE61723, and GSE154255) obtained from the Gene Expression Omnibus (GEO) repository. Significantly differentially expressed genes (DEGs) and miRNAs (DEMs), along with mRNA-miRNA interaction networks, were identified, visualized, and validated using <i>R</i> packages, enrichment analysis, protein-protein interaction (PPI) networks, and in silico validation through the UALCAN database. A total of 3242 DEGs and 95 DEMs were identified. Among these DEMs, 18 (13 downregulated and 5 upregulated) were selected as novel candidates. Target genes related to the candidate miRNAs were predicted and overlapped with DEGs. We identified 111 commonly upregulated and 129 commonly downregulated genes. Gene set enrichment analysis revealed that upregulated genes were involved in immune-related pathways, whereas downregulated genes were enriched in oncogenic signaling pathways, including MAPK and BRAF/RAF1 fusions. The mRNA-miRNA network highlighted miR-4690-5p and miR-338-3p as key regulators. <i>In silico</i> validation results confirmed that the BRD4 and LYN genes, as well as miR-16-2-3p, were significantly overexpressed, while the XBP1 gene and miR-5684 were markedly downregulated in TNBC samples. Overall, this study reveals computationally novel mRNA and miRNA expression profiles associated with metastatic and chemoresistant TNBC samples. These findings provide preliminary molecular insights may serve as tissue-specific and context-dependent biomarkers for future experimental investigations.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"102656"},"PeriodicalIF":3.3,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hydroxamate formation in the lipopeptide containing siderophore taiwachelin. 羟酸盐在含有铁载体的脂肽中形成。
IF 3.3
Biochemistry and Biophysics Reports Pub Date : 2026-06-03 eCollection Date: 2026-06-01 DOI: 10.1016/j.bbrep.2026.102660
Aaron J Gringer, Kernen P Agwaza, Isabel Da Fonseca, Pablo Sobrado
{"title":"<i>Hydroxamate formation in the lipopeptide containing siderophore</i> taiwachelin.","authors":"Aaron J Gringer, Kernen P Agwaza, Isabel Da Fonseca, Pablo Sobrado","doi":"10.1016/j.bbrep.2026.102660","DOIUrl":"10.1016/j.bbrep.2026.102660","url":null,"abstract":"<p><p><i>Cupriavidus taiwanensis</i> is a nitrogen-fixing bacterium found in root nodules of the invasive tropical weed <i>Mimosa pudica</i>. <i>C. taiwanensis</i> has been shown to grow in environments contaminated with heavy metals such as Pb, Cu, and Cd. Taiwachelin, a recently identified siderophore produced by <i>C. taiwanensis</i>, is an iron chelator that contains a hydroxamate functional group for metal binding. In its biosynthesis, a flavin-dependent N-monooxygenase (NMO) was predicted to hydroxylate l-ornithine, leading to formation of the metal binding hydroxamate moiety. Here, we report the cloning, expression, and biochemical characterization of this enzyme, herein referred to as CtNMO. CtNMO was isolated with bound FAD and catalyzed the hydroxylation of l-ornithine with a <i>k</i> <sub>cat</sub> of 0.72 ± 0.04 s<sup>-1</sup> and a <i>K</i> <sub>M</sub> of 156 ± 26 μM. A ∼25-fold preference for NADPH over NADH was observed. Expression of CtNMO as a fusion to maltose-binding protein resulted in enhanced enzymatic activity. These results validate CtNMO as an efficient l-ornithine hydroxylase and establish its potential utility in future applications, including bioremediation.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"102660"},"PeriodicalIF":3.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive characterization of the human neural stem cell line HNSC.100 as a versatile model for neurobiological research. 人类神经干细胞系HNSC.100作为神经生物学研究的通用模型的综合表征。
IF 3.3
Biochemistry and Biophysics Reports Pub Date : 2026-06-02 eCollection Date: 2026-06-01 DOI: 10.1016/j.bbrep.2026.102655
Estera Jeruzalska, Carolin Ketteler, Elisa Stützenberger, Sandra Burczyk, Larissa Möller, Dierk Niessing
{"title":"Comprehensive characterization of the human neural stem cell line HNSC.100 as a versatile model for neurobiological research.","authors":"Estera Jeruzalska, Carolin Ketteler, Elisa Stützenberger, Sandra Burczyk, Larissa Möller, Dierk Niessing","doi":"10.1016/j.bbrep.2026.102655","DOIUrl":"10.1016/j.bbrep.2026.102655","url":null,"abstract":"<p><p>Studying neural-related questions is inherently challenging due to the limited number of suitable cell models. Here, we characterize a previously reported immortalized human neural stem cell line, HNSC.100, serving as a robust model for a wide range of neurobiological research questions. The cell line expresses key neural stem cell markers, including SOX2, vimentin, nestin, and allows for efficient genetic manipulation. Furthermore, HNSC.100 cells can be differentiated into neurons, astrocytes, and oligodendrocytes, thereby covering a wide spectrum of major neural cell types. We adapted corresponding differentiation protocols and established a comprehensive panel of molecular markers to validate successful differentiation, enabling precise characterization of the resulting cell population. In addition, we provide a complete dataset of RNA expression levels for all detectable genes in HNSC.100 cells. Based on this dataset, we assembled a list of expressed genes implicated in neural disorders that can be studied with this cell line. Together, we present a detailed characterization of the HNSC.100 cell line and provide new tools and reference data to facilitate its use. This resource enables researchers to evaluate the line's suitability for specific applications and to rapidly integrate HNSC.100 cells into their experimental workflows.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"102655"},"PeriodicalIF":3.3,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Farnesoid X receptor-bile acid axis contributes to immune evasion in gastric cancer and its inhibition enhances efficacy of anti-PD-L1 therapy Farnesoid X受体-胆汁酸轴参与胃癌的免疫逃避,其抑制作用增强了抗pd - l1治疗的疗效
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-05-30 DOI: 10.1016/j.bbrep.2026.102653
Cristina Di Giorgio , Michele Biagioli , Silvia Marchianò , Carmen Massa , Ginevra Lachi , Ginevra Urbani , Martina Bordoni , Rachele Bellini , Luigi Cari , Benedetta Sensini , Maria Rosaria Sette , Elva Morretta , Maria Chiara Monti , Nicola Natalizi , Luigina Graziosi , Eleonora Distrutti , Annibale Donini , Angela Zampella , Stefano Fiorucci
{"title":"The Farnesoid X receptor-bile acid axis contributes to immune evasion in gastric cancer and its inhibition enhances efficacy of anti-PD-L1 therapy","authors":"Cristina Di Giorgio ,&nbsp;Michele Biagioli ,&nbsp;Silvia Marchianò ,&nbsp;Carmen Massa ,&nbsp;Ginevra Lachi ,&nbsp;Ginevra Urbani ,&nbsp;Martina Bordoni ,&nbsp;Rachele Bellini ,&nbsp;Luigi Cari ,&nbsp;Benedetta Sensini ,&nbsp;Maria Rosaria Sette ,&nbsp;Elva Morretta ,&nbsp;Maria Chiara Monti ,&nbsp;Nicola Natalizi ,&nbsp;Luigina Graziosi ,&nbsp;Eleonora Distrutti ,&nbsp;Annibale Donini ,&nbsp;Angela Zampella ,&nbsp;Stefano Fiorucci","doi":"10.1016/j.bbrep.2026.102653","DOIUrl":"10.1016/j.bbrep.2026.102653","url":null,"abstract":"<div><div>Gastric cancer ranks among the most prevalent malignancies globally and remains a major contributor to cancer-related mortality. Its progression is profoundly shaped by the tumor microenvironment (TME), a dynamic milieu comprising extracellular matrix components, soluble mediators, and diverse non-malignant immune populations that collectively influence tumor initiation and evolution. Although immunotherapeutic strategies have recently attracted increasing attention in the management of solid tumors, including gastric carcinoma, the determinants of immune evasion in this context are still not fully delineated. The Farnesoid X receptor (FXR), a key nuclear receptor for bile acids, has recently been implicated in regulating TME composition and immune cell recruitment within gastric tumors. Yet, how bile acid signaling contributes to the bidirectional interactions between malignant and immune cells remains largely undefined. This study aimed to investigate the role of FXR in modulating immune-regulatory networks associated with PD-L1/PD-1 in gastric cancer. RNA-seq analysis of paired gastric mucosa from 39 gastric cancer patients revealed significant molecular differences between intestinal and diffuse tumors. FXR was overexpressed in the intestinal subtype and correlated with poor prognosis. MS/MS analysis demonstrated enrichment of tumor tissues by cholic acid and chenodeoxycholic acid compared to non-neoplastic pairs, supporting the hypothesis of dysregulated bile acid metabolism. In vitro, exposure of gastric cancer cell lines and patient-derived organoids to FXR ligands increased PD-L1 expression through direct binding of FXR-responsive elements in the PD-L1 promoter. Targeting FXR may offer a therapeutic approach to improve the effectiveness of immunotherapies in intestinal gastric cancer.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102653"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167376","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}
引用次数: 0
Timosaponin B-II attenuates hemorrhagic transformation-driven acceleration of alzheimer disease-related pathology after ischemic stroke Timosaponin B-II减轻缺血性脑卒中后出血转化驱动的阿尔茨海默病相关病理加速
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-05-30 DOI: 10.1016/j.bbrep.2026.102654
Yafen Dong , Xuesong Bai , Ye Chen, Jian Wang, Qiaoyan Cui, Liming Fan, Shushu Li, Yan Qiu
{"title":"Timosaponin B-II attenuates hemorrhagic transformation-driven acceleration of alzheimer disease-related pathology after ischemic stroke","authors":"Yafen Dong ,&nbsp;Xuesong Bai ,&nbsp;Ye Chen,&nbsp;Jian Wang,&nbsp;Qiaoyan Cui,&nbsp;Liming Fan,&nbsp;Shushu Li,&nbsp;Yan Qiu","doi":"10.1016/j.bbrep.2026.102654","DOIUrl":"10.1016/j.bbrep.2026.102654","url":null,"abstract":"<div><div>Hemorrhagic transformation (HT) is a major complication of reperfusion therapy after ischemic stroke, but its impact on Alzheimer disease (AD) progression remains unclear. In this study, we used an early-stage APP/PS1 mouse model and found that HT following transient middle cerebral artery occlusion(tMCAO) aggravated cognitive impairment and promoted AD-like pathological changes, which were markedly attenuated by Timosaponin B-II (TB-II) treatment. TB-II effectively alleviated HT following tMCAO(tMCAO/HT)-induced cognitive and recognition memory deficits in APP/PS1 mice and reduced hippocampal Aβ42 production. In vitro, TB-II pretreatment reversed oxygen-glucose deprivation/reoxygenation (OGD/R) and hemin-induced increases in Aβ42 production and apoptotic propensity, as well as decreases in mitochondrial membrane potential and cell viability in N2a/APPswe cells. Mechanistically, TB-II activated NRF2, which in turn indirectly modulating GSK-3β-mediated APP phosphorylation and negatively regulated BACE1 transcription through binding promoter binding, ultimately suppressing amyloidogenic processing. Together, our findings suggest that TB-II may serve as a potential therapeutic agent against HT-associated acceleration of AD-like pathology after ischemia-reperfusion.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102654"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167377","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}
引用次数: 0
Distinct hyaluronan content and hierarchical organization of collagen-elastic fiber assemblies in subcutaneous fascia 不同的透明质酸含量和胶原弹性纤维组件在皮下筋膜的分层组织
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2026-06-01 Epub Date: 2026-03-09 DOI: 10.1016/j.bbrep.2026.102536
Natsuki Maeda , Kenshi Togashi , Yongchol Shin , Yasutada Imamura
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