Biochemistry and Biophysics Reports最新文献

{"title":"Nanochelate-based BCc1 delivery and its impact on key regulatory pathways in BALB/c breast cancer: An analysis of Beclin-1, ATG-4B, ATG-7, and mTOR expression","authors":"Fereshteh Moheb Afzali ,&nbsp;Masoumeh Heshmati ,&nbsp;Ali Salimi ,&nbsp;Somayeh Kalanaky ,&nbsp;Saideh Fakharzadeh ,&nbsp;Maryam Hafizi ,&nbsp;Mohammad Esmail Akbari ,&nbsp;Mohammad Hassan Nazaran ,&nbsp;Mehrdad Hashemi","doi":"10.1016/j.bbrep.2025.102418","DOIUrl":"10.1016/j.bbrep.2025.102418","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) ranks as the most prevalent cancer type among women globally. Nanoparticle technology, a promising approach, plays a crucial role in effective cancer diagnosis and treatment. In this context, researchers investigated the efficacy of BCc1 nanomedicine, which utilizes nanochelating technology and possesses anti-neoplastic properties, in mice with breast tumors. Notably, this study represents the first global exploration of BCc1 nanomedicine's potential to induce autophagy, a process mediated by autophagy-related genes (<em>Beclin-1</em>, <em>ATG-4B</em>, <em>ATG-7</em>, and <em>mTOR</em>), while evaluating tumor cell death.</div></div><div><h3>Methods</h3><div>In this study, female BALB/c mice bearing 4T1 mammary tumors received daily treatments with BCc1 nanomedicine for 24 consecutive days via two administration routes: intraperitoneal (i.p.) injection and oral administration by gavage. The research investigated the impact of BCc1 nanomedicine on autophagy induction. Importantly, BCc1 nanomedicine played a role in mitigating tumor cell death severity by activating essential genes. Real-time PCR facilitated detailed gene expression analysis during the 24-day treatment period.</div></div><div><h3>Results</h3><div>Cyclophosphamide and BCc1 nanomedicine exhibited distinct regulatory effects on autophagy-associated genes. <em>Beclin-1</em> expression was significantly upregulated in both cyclophosphamide-treated and BCc1-administered groups compared to controls. In BCc1-treated mice, <em>ATG-4B</em> and <em>ATG-7</em>—genes essential for autophagosome formation and maturation—were markedly downregulated across all dosing regimens. Concurrently, BCc1 induced a significant reduction in <em>mTOR</em> expression, consistent with the removal of a major inhibitory checkpoint in autophagy initiation. Taken together, these findings suggest that BCc1 exerts a stage-specific influence on autophagy, potentially enhancing its initiation phase while attenuating subsequent maturation steps.</div></div><div><h3>Conclusion</h3><div>In summary, BCc1 nanomedicine demonstrates therapeutic potential in BC, in part through the modulation of autophagy pathways. The observed gene expression profile—characterized by <em>mTOR</em> suppression and <em>Beclin-1</em> upregulation alongside reduced <em>ATG-4B</em> and <em>ATG-7</em> expression—indicates a selective enhancement of autophagy initiation, coupled with alterations in autophagosome maturation. This nuanced modulation of autophagy may contribute to BCc1's anti-tumor activity and warrants further investigation into its stage-specific mechanistic effects in cancer therapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102418"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938390","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":"Mammalian fatty acid synthase and O-GlcNAc transferase preferentially interact via their respective N-terminal regions","authors":"Dimitri Vanauberg,&nbsp;Céline Schulz,&nbsp;Guillaume Brysbaert,&nbsp;Nessim Raouraoua,&nbsp;Peggy Mistarz-Gruau,&nbsp;Marc F. Lensink,&nbsp;Anne-Sophie Vercoutter-Edouart,&nbsp;Tony Lefebvre","doi":"10.1016/j.bbrep.2025.102427","DOIUrl":"10.1016/j.bbrep.2025.102427","url":null,"abstract":"<div><div>Fatty Acid Synthase (FASN) is a central enzyme in the <em>de novo</em> lipogenesis pathway. By producing fatty acids, FASN is implicated in numerous crucial cellular processes, but it is also frequently overexpressed in cancer. <em>O</em>-GlcNAc Transferase (OGT) governs the addition of N-acetylglucosamine residues onto cytosolic, nuclear and mitochondrial proteins. Like FASN, OGT actively participates in carcinogenesis. We previously showed that OGT regulates FASN in different <em>ex vivo</em> and <em>in vivo</em> models. Reciprocally, FASN promotes OGT expression and activity. The two enzymes physically interact together and contribute to cancer cell survival. It is therefore fundamental to define the respective interaction region of each enzyme to explore new therapeutic solutions for patients suffering from cancer. By using the hepatocarcinoma cell line Hep3B, we show thanks to two series of deletion mutants that both enzymes preferentially interact <em>via</em> their respective N-terminal regions. Analysis of the <em>O</em>-GlcNAc status of the various FASN deletion mutants shows that stronger interaction with OGT correlates with higher glycosylation, suggesting that OGT catalyzes the transfer of GlcNAc with limited substrate specificity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102427"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938486","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":"Humanin improves bone health in a glucocorticoid-treated mouse model of Duchenne muscular dystrophy","authors":"Therése Cedervall ,&nbsp;Baptiste Jude ,&nbsp;Ferdinand von Walden ,&nbsp;Lilly Velentza ,&nbsp;Johanna T. Lanner ,&nbsp;Thomas Sejersen ,&nbsp;Farasat Zaman ,&nbsp;Lars Sävendahl","doi":"10.1016/j.bbrep.2025.102421","DOIUrl":"10.1016/j.bbrep.2025.102421","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a progressive muscle disease for which glucocorticoid (GC) treatment is standard therapy. Patients typically suffer from short stature and osteoporosis, caused by the underlying disease and adverse effects of GCs. We investigated whether the mitochondrial peptide humanin (HNG) could prevent GC-induced growth retardation and osteoporosis in mouse models of DMD.</div><div>Male mdx mice (B10.mdx and D2.mdx) were treated with GCs, with/without HNG, from 5 to 9 weeks of age using two different treatment regimens. Tibial growth was monitored by weekly X-ray imaging; growth plates analyzed with immunohistochemistry and histomorphometry; and bone structure examined using peripheral quantitative computed tomography. Effects on skeletal muscle were evaluated by immunohistochemistry, qPCR, and <em>ex vivo</em> force measurements.</div><div>D2.mdx, but not B10.mdx, showed decreased bone growth and impaired bone structure compared with wild type (WT). D2.mdx also displayed increased growth plate height with lower endogenous humanin expression than D2.WT. GC treatment caused growth retardation and reductions in cortical bone area, thickness, and mineral content. Co-administration with HNG prevented bone growth impairment at one week of treatment and mitigated GC adverse effects on cortical bone in B10.mdx mice. Adding HNG to GCs did not exacerbate skeletal muscle pathology; in fact, HNG had a mild enlarging effect on muscle fibers.</div><div>These data suggest that HNG is a potential candidate for improving bone health in DMD during GC therapy. Further <em>in vivo</em> studies are needed to determine optimal HNG dosing and to assess the effects of long-term treatment on skeletal muscle function.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102421"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938488","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":"Melatonin alleviates gentamicin-induced acute kidney injury through the Keap1/Nrf2/HO-1 signaling pathway","authors":"Ningning Li ,&nbsp;Xianghua Liu ,&nbsp;Wei Liu ,&nbsp;Saifei Li ,&nbsp;Yanfei Lei ,&nbsp;Baoying Wang","doi":"10.1016/j.bbrep.2025.102433","DOIUrl":"10.1016/j.bbrep.2025.102433","url":null,"abstract":"<div><div>Drug-related factors represent a primary cause of acute kidney injury. Gentamicin (GM), while being one of the most effective and commonly used clinical agents against Gram-negative bacteria, frequently induces nephrotoxicity and triggers acute kidney injury during treatment. Melatonin, a natural antioxidant produced by the pineal gland, has been shown in recent studies to mitigate drug-induced nephrotoxicity. This study aimed to delineate the dose-dependent effects and underlying mechanisms of GM-induced acute kidney injury, along with the protective role of melatonin. Results demonstrated that GM administration elicited dose-dependent nephrotoxicity in rats, significantly elevating urinary biomarkers of tubular injury (KIM-1 and NGAL) and serum markers of renal dysfunction (BUN and SCr) at doses ≥50 mg/kg. Histopathological analysis revealed progressive renal damage including brush border loss, epithelial necrosis, basement membrane disruption, and interstitial inflammation. GM further exacerbated renal oxidative stress, depleting SOD and GSH while elevating MDA levels. Mechanistically, GM dose-dependently upregulated Keap1 and downregulated NRF2 expressions, consequently suppressing downstream antioxidants (GPX1, NQO1, HO-1). However, melatonin treatment significantly ameliorated high-dose GM-induced acute kidney injury by normalizing biochemical markers of renal impairment, attenuating histopathological damage, restoring antioxidant capacity, and reactivating the KEAP1/NRF2 pathway through suppression of Keap1 while enhancing NRF2 and its target proteins (GPX1/NQO1/HO-1) to nearly double of GM-H group levels, confirming its renoprotective role against GM-induced oxidative injury.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102433"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938391","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":"Normal spermatogenesis and fertility in Spmip8 deficiency male mice","authors":"Zeling Zhang ,&nbsp;Meihong Hu ,&nbsp;Di Yan,&nbsp;Yuanqi Zhao,&nbsp;Wen Tao,&nbsp;Shengyuan Chen,&nbsp;Meijie Qi,&nbsp;Lei Luo,&nbsp;Xiaohua Jiang,&nbsp;Bo Xu,&nbsp;Shun Bai","doi":"10.1016/j.bbrep.2025.102406","DOIUrl":"10.1016/j.bbrep.2025.102406","url":null,"abstract":"<div><div>Spmip8, also known as Tepp, is a protein-coding gene which highly conserved in the mammals. Although SPMIP8 has been reported to be highly expressed in the testis, the function of SPMIP8 in spermatogenesis and male fertility remain unknown. In this study, we used CRISPR/cas9-mediated genome editing system to generate <em>Spmip8</em>-deficient mice. The phenotype of <em>Spmip8</em> knockout (KO) male mice was performed by fertility tests, histology, and immunofluorescence. SPMIP8 is localization to the flagella of elongating spermatids in testis. <em>Spmip8</em> KO male mice exhibited normal fertility. No significant differences were found in sperm count, motility, morphology and kinematic parameters between WT and <em>Spmip8</em> KO mice. Furthermore, no detectable defects in spermatogenesis were found in KO mice. The transcription level of several <em>Spmip</em> genes (<em>Spmip1</em>, <em>Spmip2</em>, <em>Spmip3</em>, <em>Spmip7</em> and <em>Spmip11</em>) was elevated in the testes of <em>Spmip8</em> knockout mice, suggesting that <em>Spmip8</em> gene in male fertility could be compensated by other <em>Spmip</em> family members. Overall, the findings of this study suggest that <em>Spmip8</em> is not an essential gene for male fertility in mice. Our study helps researchers avoid duplication and repetitive work and explore genes that are integral to spermatogenesis and male fertility.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102406"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938392","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":"Functional classification of antineutrophil cytoplasmic antibody (ANCA) and its relation with clinical parameters of ANCA-associated vasculitis","authors":"Mai Taniguchi ,&nbsp;China Washio ,&nbsp;Momo Uchizawa ,&nbsp;Naho Ogawa ,&nbsp;Riku Manabe ,&nbsp;Suishin Arai ,&nbsp;Hodaka Ogawa ,&nbsp;Yuka Nishibata ,&nbsp;Sakiko Masuda ,&nbsp;Daigo Nakazawa ,&nbsp;Utano Tomaru ,&nbsp;Yoshihiro Arimura ,&nbsp;Koichi Amano ,&nbsp;Yukio Yuzawa ,&nbsp;Ken-Ei Sada ,&nbsp;Tatsuya Atsumi ,&nbsp;Hiroaki Dobashi ,&nbsp;Masayoshi Harigai ,&nbsp;Seiichi Matsuo ,&nbsp;Hirofumi Makino ,&nbsp;Akihiro Ishizu","doi":"10.1016/j.bbrep.2025.102428","DOIUrl":"10.1016/j.bbrep.2025.102428","url":null,"abstract":"<div><div>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by serum ANCA and systemic small-vessel vasculitis. Neutrophils are primed to express ANCA antigens on the plasma membrane. ANCA binding to the antigens can transduce signals into neutrophils, releasing reactive oxygen species (ROS) and contributing to AAV development. ANCA-mediated signals are transduced via two pathways: ANCA antigens crosslinked by ANCA, and Fcγ receptor (FcγR), to which the Fc portion of ANCA binds. This study aimed to demonstrate the association of ANCA-mediated neutrophil activation pathways with clinical manifestations of AAV, including renal dysfunction and kidney survival at 6 months after treatment. For this purpose, IgG was extracted from the serum of AAV patients before treatment (n = 112), and ROS production from neutrophils exposed to IgG and its suppression by FcγR inhibitors (FcX) were assessed. IgG exhibiting higher ROS production than control IgG was classified as ROS-inducing ANCA and the others as ROS-noninducing ANCA. The former was subclassified into antigen-driven ANCA and FcγR-driven ANCA according to whether the ROS production suppression rate by FcX was &lt;50 % or ≧50 %, respectively. As a result, ANCA was classified into ROS-inducing antigen-driven ANCA (n = 74), ROS-inducing FcγR-driven ANCA (n = 22), and ROS-noninducing ANCA (n = 16). Serum levels of blood urea nitrogen and creatinine were significantly higher in patients with ROS-inducing FcγR-driven ANCA than in those with ROS-noninducing ANCA. Patients with ROS-inducing FcγR-driven ANCA had a significantly lower kidney survival rate 6 months after treatment than other patients. The collective findings suggest that ROS-inducing FcγR-driven ANCA may predict poor kidney prognosis in AAV.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102428"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938992","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":"The TAAR1 antagonist EPPTB ameliorates colitis via serotonin inhibition","authors":"Leyi Luo ,&nbsp;Tong Zhang ,&nbsp;Linlin Liang ,&nbsp;Weixin Chen ,&nbsp;Tao Wang ,&nbsp;Wenke Chen ,&nbsp;Haitao Xiao ,&nbsp;Guangtao Zhang","doi":"10.1016/j.bbrep.2025.102432","DOIUrl":"10.1016/j.bbrep.2025.102432","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is characterized by gut dysbiosis and impaired microbial metabolite signaling. Emerging evidence suggests that gut microbial metabolites, such as trace amines (tryptamine, phenethylamine, and tyramine), function as endogenous TAAR1 agonists and may contribute to IBD pathogenesis. Our study identified elevated fecal trace amine levels in ulcerative colitis (UC) patients and DSS-induced colitis mice. In vitro, exposure to these trace amines enhanced 5-HT secretion in QGP-1 cells and ex vivo mouse colonic tissues, and this effect could be blocked by the TAAR1 antagonist EPPTB. In vivo, EPPTB treatment significantly mitigated DSS-induced colitis, as demonstrated by reduced weight loss, improved disease activity index (DAI), preserved colon length, and attenuated histopathological damage. Moreover, TAAR1 blockade reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and increased IκB-α expression, restored intestinal barrier integrity (upregulating occludin and ZO-1, while downregulating cclaudin-2), and lowered colonic 5-HT levels by suppressing TPH1 expression. These findings suggest that TAAR1 inhibition alleviates colitis by modulating 5-HT signaling, positioning it as a promising therapeutic target for IBD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102432"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938487","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":"Live cell imaging of exogenous α-synuclein fibrils in primary microglia and neuron co-cultures","authors":"C. Paquette,&nbsp;T. Charlton,&nbsp;N. Prowse,&nbsp;T. Fortin,&nbsp;H. Sun,&nbsp;S. Hayley","doi":"10.1016/j.bbrep.2025.102416","DOIUrl":"10.1016/j.bbrep.2025.102416","url":null,"abstract":"<div><div>α-synuclein (α-syn) rich Lewy bodies are a prominent pathological feature of Parkinson's disease (PD), with intra-cellular accumulation occurring in neurons and possibly microglia. Tracking α-syn movement between the two different cell types is of critical importance in determining how pathology spreads. We hypothesized that the separate pre-treatment of either primary cortical neurons or microglia with exogenous α-syn preformed fibrils (PFFs) will foster a cytotoxic environment when co-cultured with the opposite naïve cell type. To this end, using real time live cell imaging, we found an accumulation of Alexa Fluor 488 labelled α-syn PFFs in both microglia and neurons. In the co-cultures, the labelled-PFFs showed differing patterns of spread to non-seeded cells. The PFF treatment also provoked cellular loss that increased with the passage of time and induced marked vacuolation and changes in microglial morphology. Microglia appeared to accumulate PFFs from morphologically compromised neurons and shifted to a predominately dystrophic and “foamy enlarged fried egg” morphology over time and was associated with a reduction in levels of the anti-inflammatory cytokine, interleukin-4 (IL-4). We currently provide a novel <em>in vitro</em> co-culture model that allows for tracking α−syn spread between primary cortical microglia and neurons.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102416"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938483","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":"Comparative effects of a TLR7/8 agonist and doxorubicin on immune checkpoint modulation and apoptosis in 4T1 breast cancer cells","authors":"Nazanin Joudaki ,&nbsp;Mohsen Tehrani ,&nbsp;Abolghasem ajami ,&nbsp;Saeid Taghiloo","doi":"10.1016/j.bbrep.2025.102440","DOIUrl":"10.1016/j.bbrep.2025.102440","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is still one of the challenges of medical science, despite fast and remarkable advancements in diagnosis and new therapy approaches. This study aims to explore the individual effects of TLR7/8 agonists and to compare their cytotoxic properties with those of the chemotherapy drug doxorubicin on 4T1 breast cancer cells, as well as to evaluate their role in the modulation of immune checkpoint molecules.</div></div><div><h3>Methods</h3><div>4T1 cancer cells were treated with the TLR7/8 agonist R848 and doxorubicin for a duration of 48 h. First, the viability of the cells was assessed using the MTT method. The relative expression of mRNA for Gal-9, PD-L1, and PVR was analyzed with HPRT serving as a housekeeping gene. Finally, an apoptosis test was conducted to evaluate the cytotoxic effects of R848 and doxorubicin on 4T1 cells. And the wound healing assay was completed in order to assess the migratory potential of 4T1 cells after treatment with R848 and doxorubicin.</div></div><div><h3>Results</h3><div>The expression of the PVR and Gal-9 genes in the group treated with R848 showed a decrease compared to the control group, although this change was not statistically significant. In contrast, the expression of PD-L1 and PVR in the group treated with doxorubicin increased significantly when compared to both the control group and the R848 treated group. Additionally, the total apoptosis rate in both the R848 and doxorubicin treatment groups was significantly higher than that in the control group. After 24 h post-scratch, control 4T1 cells showed about 50 % wound closure, while R848 reduced it to 35 %. Doxorubicin lowered migration to under 10 %. By 48 h, control and R848 nearly closed the wound, unlike the DOX group.</div></div><div><h3>Conclusion</h3><div>R848 and doxorubicin possess anti-proliferative and pro-apoptotic effects on 4T1 cells, doxorubicin effectively induces cell death and boosts immune checkpoint gene expression, while R848 fosters early apoptosis without raising checkpoint ligand expression.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102440"},"PeriodicalIF":2.2,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938384","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":"Pulmonary edema following subarachnoid hemorrhage is associated with impairment of pulmonary vascular endothelial glycocalyx","authors":"Nozomi Sasaki ,&nbsp;Yusuke Egashira ,&nbsp;Hideshi Okada ,&nbsp;Chihiro Takada ,&nbsp;Shinomi Sasaibe ,&nbsp;Masaki Kumagai ,&nbsp;Yoshiki Kuse ,&nbsp;Shinsuke Nakamura ,&nbsp;Hirofumi Matsubara ,&nbsp;Yukiko Enomoto ,&nbsp;Toru Iwama ,&nbsp;Tsuyoshi Izumo ,&nbsp;Hideaki Hara ,&nbsp;Masamitsu Shimazawa","doi":"10.1016/j.bbrep.2025.102420","DOIUrl":"10.1016/j.bbrep.2025.102420","url":null,"abstract":"<div><div>Although neurogenic pulmonary edema (NPE) often occurs after aneurysmal subarachnoid hemorrhage (SAH), the mechanism of NPE progression after SAH remains unclear. This study investigates whether pulmonary endothelial glycocalyx (PEG) impairment accompanies NPE after SAH. Accordingly, SAH was induced by endovascular perforation in male mice. The lung tissues of the mice were removed 24 h after SAH induction. The degree of pulmonary edema and lung injury, and the extent of PEG injury were assessed. Water content of lung tissue by the wet/dry method in the SAH group was significantly increased compared to that in the sham group (81.7 % vs. 78.8 %, <em>P</em> &lt; 0.01), which suggested NPE following SAH. Lung injury score by hematoxylin and eosin staining in the SAH group, assessed using a semiquantitative scoring system, was also significantly worse than that in the sham group (7.1 vs. 1.2, <em>P</em> &lt; 0.001). Scanning electron microscopy images clearly demonstrated that the moss-like glycocalyx lined the endothelial lumen without any interruption in sham mice, whereas those microstructures were severely devastated in SAH mice. Moreover, the fluorescence intensity of tomato lectin was significantly reduced in SAH mice compared to that in sham mice (13.3 vs. 30.7, <em>P</em> &lt; 0.001), thereby indicating the loss of PEG. Our results indicate that PEG, which is essential for regulating vascular permeability, is severely impaired after experimental SAH. Maintaining the integrity of PEG is a promising therapeutic strategy for NPE after SAH.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102420"},"PeriodicalIF":2.2,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797520","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}