Biochemical and biophysical research communications最新文献

{"title":"High-dose vitamin C blocks HOCl production by Myeloperoxidase: A potential therapeutic strategy","authors":"Alexander V. Peskin,&nbsp;Nicholas J. Magon,&nbsp;Stephanie M. Bozonet","doi":"10.1016/j.bbrc.2025.152213","DOIUrl":"10.1016/j.bbrc.2025.152213","url":null,"abstract":"<div><div>High-dose vitamin C therapy for cancer, originally advocated by Linus Pauling (Proc Natl Acad Sci, 1976, 73, 3685–3689), remains a subject of ongoing debate. In this study, we investigate why only pharmacological doses are effective and explore the reasons behind inconsistent therapeutic outcomes. Our data suggest that the bona fide cause of toxicity was oxidized vitamin C rather than hydrogen peroxide. We found that vitamin C at millimolar concentrations, directly inhibits hypochlorous acid generation by myeloperoxidase, through competition with chloride rather than by scavenging the hypochlorous acid that is formed. Products of vitamin C oxidation reacted with the thiols of peroxiredoxin 2 and GAPDH, but failed to react with the cysteine of p16^INK4a. The growth and viability of Jurkat cells were affected by oxidized vitamin C. These experiments were conducted in the presence of catalase, demonstrating that the biological effects were due to the products of vitamin C oxidation and not hydrogen peroxide. These findings may have practical implications for the treatment of cancer and diseases in which the deleterious effects of neutrophil activation are observed. For intravenous administration of pharmacological vitamin C to have a beneficial effect, its concentration in the blood must be maintained at millimolar levels and this can only be achieved via maintenance infusion. As a proof-of-concept, our data suggest that to enhance anticancer therapy interventions, it is crucial to implement treatments that facilitate the oxidation of vitamin C in the bloodstream.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152213"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321775","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":"Innovative melanoma treatment: Acoustic-sensitive foam induces tumor cavitation via the nibbling effect","authors":"Huichao Xie ,&nbsp;Wan Li ,&nbsp;Yongfeng Chen ,&nbsp;Ke Dang ,&nbsp;Xiaoyu Huang ,&nbsp;Bao Li ,&nbsp;Tong Yu ,&nbsp;Haoran Niu ,&nbsp;Di Song ,&nbsp;Shimei Yang ,&nbsp;Shuxin Gao ,&nbsp;Feiyang Huang ,&nbsp;Tianzhi Yang ,&nbsp;Keda Zhang ,&nbsp;Yan Kang ,&nbsp;Pingtian Ding","doi":"10.1016/j.bbrc.2025.152231","DOIUrl":"10.1016/j.bbrc.2025.152231","url":null,"abstract":"<div><div>Melanoma, a malignant tumor originating from melanocytes, is characterized by rapid proliferation and high metastatic potential. Addressing the urgent clinical need for effective tumor-suppressive agents to inhibit melanoma progression, this study introduces a novel therapeutic strategy utilizing acoustic-sensitive foam, termed PFH/TA9. This foam integrates perfluorohexane (PFH), an acoustic-sensitive material, with tranexamic acid nonyl ester hydrochloride (TA9), a cationic surfactant. Administered as an aqueous dispersion, PFH/TA9 was injected directly into the tumor site, where it underwent liquid-to-gas phase transition under low-intensity focused ultrasound radiation. This transition generated PFH bubbles, serving as a gas source for foam formation. The intense ultrasonic cavitation effect induced by LIFU supplied the mechanical force necessary for foam generation, while TA9 molecules aligned at the PFH gas-water interface, reducing surface tension and stabilizing the foam. The stabilized foam extensively contacted tumor tissue, initiating a “nibbling effect” that progressively disrupted tumor cells by damaging cell membranes and inducing tissue cavitation. The acoustic-sensitive foam exhibited a TUNEL⁺ cell rate of 20.91 % and tumor cavitation area of 52.78 % in central tumor regions at 24h post-treatment, achieving 89.37 % tumor inhibition by day 16. By leveraging the cavitation and nibbling effects of acoustic-sensitive foam, this innovative therapeutic strategy demonstrated highly efficient containment of melanoma.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152231"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335993","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":"Coelenterazine sulfotransferase from the luminous squid Watasenia scintillans","authors":"Nowshin Farjana ,&nbsp;Yasuo Mitani ,&nbsp;Souichiro Kato ,&nbsp;Shusei Kanie","doi":"10.1016/j.bbrc.2025.152215","DOIUrl":"10.1016/j.bbrc.2025.152215","url":null,"abstract":"<div><div>The squid <em>Watasenia scintillans</em> is a luminous marine organism that utilizes coelenterazine 2,6-disulfate (CTZ 2,6-SO₃H) as its luminous substrate. CTZ 2,6-SO₃H, a derivative of coelenterazine (CTZ), can be chemically synthesized by sulfating CTZ at its two phenolic hydroxyl groups. CTZ is produced by certain marine plankton and is widely distributed among marine organisms through the food web. However, CTZ 2,6-SO₃H has been identified only in <em>W</em>. <em>scintillans</em>, and it remains unclear whether the squid biosynthesizes CTZ 2,6-SO₃H from CTZ. In this study, we investigated the presence of a sulfotransferase (SULT) responsible for the sulfation of CTZ in <em>W</em>. <em>scintillans</em>. RNA-seq analysis of the squid's arm photophore revealed a putative SULT gene, which was successfully expressed in <em>Escherichia coli</em>. The recombinant protein exhibited sulfation activity toward CTZ in the presence of 3′-phosphoadenosine 5′-phosphosulfate (PAPS), as confirmed by ultra-performance liquid chromatography-photodiode array detection-mass spectrometry (UPLC-PDA-MS) analysis. The sulfated product was not CTZ 2,6-SO₃H but rather CTZ 2-monosulfate (CTZ 2-SO₃H). These findings suggest that <em>W</em>. <em>scintillans</em> possesses a biosynthetic pathway for CTZ 2,6-SO₃H from CTZ, which may involve additional SULT(s).</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152215"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471720","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":"CD5L is a target of transcription factor Nrf2","authors":"Sharadha Dayalan Naidu ,&nbsp;Abel D. Ang ,&nbsp;Charlotte Lim Jia Yee ,&nbsp;Oliver J. Read ,&nbsp;Tom S. Dixon ,&nbsp;Elena V. Knatko ,&nbsp;Aileen Sandilands ,&nbsp;Maureen Higgins ,&nbsp;Dorothy Kisielewski ,&nbsp;John D. Hayes ,&nbsp;Tadashi Honda ,&nbsp;Takafumi Suzuki ,&nbsp;Masayuki Yamamoto ,&nbsp;Albena T. Dinkova-Kostova","doi":"10.1016/j.bbrc.2025.152225","DOIUrl":"10.1016/j.bbrc.2025.152225","url":null,"abstract":"<div><div>CD5 antigen-like (CD5L), also known as apoptosis inhibitor expressed by macrophages (AIM), is a secreted protein produced by macrophages, which has both cell-autonomous and non-autonomous functions: it has been implicated in multiple biological processes, including inflammation, infection, and fibrosis. The transcriptional regulation of <em>CD5L</em> is complex, and a comparison of the proteomes of bone marrow-derived macrophages from mice with graded expression of transcription factor NF-E2 p45-related factor 2 (Nrf2) indicated that Nrf2 controls expression of the <em>CD5L</em> gene. Using genetic and pharmacological means to increase or decrease Nrf2 activity, we found a correlation between the abundance of Nrf2 and <em>CD5L</em> expression in both murine macrophages and primary human monocyte-derived macrophages. Furthermore, the potency of small-molecule Nrf2 activators with distinct mechanisms of action and different potencies, correlated with the extent of CD5L expression, both at the mRNA and the secreted protein levels. Conversely, depletion of Nrf2 resulted in a significant decrease in CD5L mRNA levels. Chip-seq analysis showed Nrf2 binding 20,000 bp upstream of the <em>Cd5l</em> promoter, a region containing sequences resembling the antioxidant response element (ARE, 5′-TGACNNNGC-3′) Nrf2-binding motif. Deletion of two of these sequences by CRISPR/Cas9 gene editing led to a profound decrease in CD5L mRNA levels, confirming the critical role of these ARE-like sequences in controlling <em>CD5L</em> expression. Recombinant CD5L (rCD5L) suppressed transforming growth factor β (TGFβ)-directed fibrogenic responses in human lung fibroblasts, suggesting that Nrf2 activators, such as the clinically used omaveloxolone (RTA-408), could protect against pulmonary fibrosis by boosting the levels of CD5L.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152225"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329704","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":"Carbidopa ameliorates high-fat diet-induced insulin resistance by suppressing gut-derived tryptamine/phenethylamine and systemic 5-HT levels","authors":"Liping Wen ,&nbsp;Jiayu He ,&nbsp;Yanling Li ,&nbsp;Jie Ma ,&nbsp;Jiao peng","doi":"10.1016/j.bbrc.2025.152234","DOIUrl":"10.1016/j.bbrc.2025.152234","url":null,"abstract":"<div><div>Obesity and type 2 diabetes mellitus (T2DM) are major global health burdens, with insulin resistance (IR) as a key pathological driver. This study explores carbidopa, a selective aromatic <span>l</span>-amino acid decarboxylase inhibitor, as a modulator of gut-derived metabolites to alleviate high-fat diet (HFD)-induced IR. We observed that HFD markedly increased fecal tryptamine and phenethylamine levels, which positively correlated with elevated serum 5-hydroxytryptamine (5-HT). Carbidopa treatment suppressed gut production of these metabolites, reducing circulating 5-HT and improving insulin sensitivity in HFD-fed mice. Notably, carbidopa lowered fasting blood glucose, enhanced glucose tolerance, and promoted hepatic Akt phosphorylation. Our results demonstrate that carbidopa attenuates HFD-induced IR by disrupting gut microbiota-dependent synthesis of tryptamine and phenethylamine, thereby reducing systemic 5-HT. These findings identify the gut microbiota-tryptamine/phenethylamine-5-HT axis as a pivotal pathway in IR pathogenesis and position carbidopa as a promising therapeutic candidate for metabolic disorders. Further clinical investigations are needed to validate its translational potential in T2DM management.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152234"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336035","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":"Double-stranded RNA adenosine deaminases suppress ferroptosis through regulating SCD1","authors":"Yui Taek Lee,&nbsp;Ji Woo Kang,&nbsp;Soon Ji Yoo","doi":"10.1016/j.bbrc.2025.152218","DOIUrl":"10.1016/j.bbrc.2025.152218","url":null,"abstract":"<div><div>Double-stranded RNA adenosine deaminases 1 and 2 (ADAR1/2) are enzymes that convert adenosine to inosine (A-to-I), a major RNA editing event. A-to-I editing is strongly correlated with cancer progression and drug resistance. While the role of ADAR1/2 in apoptosis regulation in certain cancer types is well-characterized, their potential involvement in ferroptosis has not been explored. In this study, we report that ADAR1/2 are upregulated in cervical, breast, and colon cancers but have no impact on drug-induced apoptosis. Depletion of ADAR1/2 resulted in increased lipid droplets and downregulated Stearoyl-CoA desaturase 1 (SCD1), a lipogenic enzyme that protects cells from lipid peroxidation and ferroptosis. ADAR1/2 and SCD1 expressions are positively correlated at both mRNA and protein levels in cancers with elevated ADAR1/2. Cells depleted of ADAR1/2 were sensitized to RSL3-induced ferroptosis. Furthermore, cells stably overexpressing wild-type ADAR1 (WT) remained resistant to ferroptosis with strong SCD1 expression, whereas cells with an RNA editing-inactive mutant (EAA) were sensitive with diminished SCD1 levels. WT cells became susceptible to RSL3-induced ferroptosis when SCD1 was depleted. These results indicate that ADAR1/2 suppress ferroptotic cell death via RNA editing activity, specifically through SCD1 regulation.</div><div>Collectively, our findings highlight the suppressive role of ADAR1/2 in ferroptosis and reveal a novel function of ADAR1/2 in regulating this process. These results suggest that targeting ADAR1/2 could offer a promising strategy to overcome chemotherapeutic resistance in cancers with elevated RNA editing.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152218"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329712","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":"Schisandrin A induces osteoblast differentiation to treat glucocorticoid-induced osteoporosis through activating Wnt pathway","authors":"Yuanliang Ai ,&nbsp;Xuehua Xie ,&nbsp;Ying Guo ,&nbsp;Jie Zhao ,&nbsp;Yanfei Xu ,&nbsp;Tao Wang ,&nbsp;Yinghong Huang ,&nbsp;Wenze Huang ,&nbsp;Taohong Ma ,&nbsp;Yan Luo ,&nbsp;Weibo Wen ,&nbsp;Huantian Cui","doi":"10.1016/j.bbrc.2025.152230","DOIUrl":"10.1016/j.bbrc.2025.152230","url":null,"abstract":"<div><div>Schisandrin A (SchA) efficacy in addressing glucocorticoid-induced osteoporosis (GIOP) remains unexplored, and its underlying mechanisms are yet to be clarified. We developed a GIOP mouse model. The efficacy of SchA was assessed comprehensively through micro-CT analysis, biomechanical testing. Using transcriptomic profiling, we investigated the impact of SchA on gene expression in the bone tissue of GIOP mice. Additionally, biochemical assays and Western blot were performed to evaluate SchA's effects on osteogenic growth-related factors in GIOP mice. To complement these findings, we first established an osteoblast injury model to validate the effects of SchA on osteoblast differentiation. We then assessed the activity of the Wnt/β-catenin signaling pathway using a dual luciferase assay and further identified its molecular targets. Our findings demonstrate that SchA intervention significantly improved bone mass parameters, bone mineral density, and bone volume fraction, as well as bone strength indicators in GIOP mice. SchA treatment also elevated serum calcium and phosphorus levels and mitigated pathological damage in the femur. Transcriptomic analysis revealed that SchA upregulated key transcription factors associated with osteoblast differentiatio. Western blot analysis confirmed that SchA intervention increased the expression of key proteins involved in the Wnt signaling pathway. <em>In vitro</em> experiments further validated that SchA upregulated differentiation factors and key Wnt pathway proteins in osteoblasts. The TOP/FOP flash ratio in osteoblasts increased noticeably after SchA treatment, indicating activation of the Wnt/β-catenin signaling pathway. However, when Wnt5a was inhibited using Box5, the regulatory effect of SchA on osteoblast differentiation was abolished. This study comprehensively evaluates the therapeutic effects of SchA on GIOP and suggests that its efficacy likely involves activation of the Wnt signaling pathway in bone cells, thereby promoting osteoblast differentiation and activation, and facilitating bone formation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152230"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338396","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":"The extracellular matrix glycoprotein tenascin-C supports the enriched environment-stimulated neurogenesis in the adult dentate gyrus of mice","authors":"Milena Korenić ,&nbsp;Andrej Korenić ,&nbsp;Vera Stamenković ,&nbsp;Nese Aysit ,&nbsp;Pavle Andjus","doi":"10.1016/j.bbrc.2025.152232","DOIUrl":"10.1016/j.bbrc.2025.152232","url":null,"abstract":"<div><div>The extracellular matrix glycoprotein tenascin C (TnC) is implicated in a variety of processes ranging from cell proliferation and adhesion to synaptic plasticity. The contribution of TnC to neurogenesis related processes in the adult hippocampus, however, remains unclear. To address this question, hippocampal sections were immunostained for the proliferation marker Ki67 and for neuroblast marker doublecortin (DCX). Laser scanning confocal microscopy revealed that TnC - deficiency does not alter either the size of Ki67+ or DCX + cellular populations in the subgranular zone (SGZ) compared to the control animals. Super-resolution Airyscan confocal microscopy enabled the investigation of the complexity of dendritic trees of DCX + cells with the analysis of the dendritic tree complexity parameters. The results show that the dendritic tree complexity of developing neurons is not dependent on the presence of TnC. However, reinforcement of adult neurogenesis by the exposure to enriched environment (EE) revealed that TnC- deficient mice have a reduced number of DCX + cells compared to wild type littermates. This study indicates that TnC might not contribute to the basal levels of adult neurogenesis in the hippocampus, while on the other hand it gains importance in the generation of the positive effect of EE.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152232"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338398","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":"Beyond energy metabolism: ketogenic diet and β-hydroxybutyrate protect against intestinal ischemia-reperfusion injury through anti-inflammatory and barrier-preserving effects","authors":"Fei-xiang Wang ,&nbsp;Na Wei ,&nbsp;Shi-yu Dai ,&nbsp;Xu Zhong ,&nbsp;Guo Mu ,&nbsp;Xin Fan ,&nbsp;Si-rui Chen ,&nbsp;Ye Chen ,&nbsp;Jun Zhou","doi":"10.1016/j.bbrc.2025.152227","DOIUrl":"10.1016/j.bbrc.2025.152227","url":null,"abstract":"<div><div>Intestinal ischemia-reperfusion injury (IRI) is a significant clinical challenge with limited effective treatments. This study investigated the protective effects of ketogenic diet (KD) and β-hydroxybutyrate (BHB) against intestinal IRI using mouse models and intestinal organoids. Following two weeks of KD or BHB administration, mice were subjected to superior mesenteric artery occlusion (60 min) and reperfusion (4 h). Both interventions significantly elevated blood BHB levels and reduced fasting glucose. KD and BHB markedly attenuated intestinal villous damage, preserved epithelial barrier function (E-cadherin, Occludin, ZO-1), maintained mitochondrial integrity, reduced inflammatory cytokines (IL-6, IL-1β, TNF-α), and improved 72-h survival rates, with KD demonstrating superior efficacy. In intestinal organoid oxygen-glucose deprivation models, BHB exhibited differential protective effects at two tested concentrations (2 mM vs. 5 mM), with enhanced protection at the higher concentration on cellular viability, structural integrity, and inflammatory responses. These findings provide the first evidence that ketogenic interventions protect against intestinal IRI through multiple mechanisms including inflammatory suppression and barrier preservation, suggesting potential clinical applications in intestinal IRI prevention and management, though detailed mechanistic elucidation requires further investigation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152227"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313979","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":"The therapeutic effect of topical injection of adipose stem cell-derived extracellular vesicles at different time intervals on wound healing in mice","authors":"Qiang Niu ,&nbsp;Yan Guo ,&nbsp;Zhou Zhang ,&nbsp;Jing Gong ,&nbsp;Fei Liu ,&nbsp;Yu Kong","doi":"10.1016/j.bbrc.2025.152223","DOIUrl":"10.1016/j.bbrc.2025.152223","url":null,"abstract":"<div><div>Adipose-derived stem cell extracellular vesicles (ADEVs) have emerged as a promising biotherapeutic agent, demonstrating efficacy in treating various skin diseases, including wound healing, through local injection. The concentration of ADEVs and the optimal injection interval are critical factors influencing their therapeutic outcomes. However, the optimal dosage and injection intervals for ADEVs in wound healing remain to be elucidated. In this study, we harvested ADEVs from adipose-derived stem cells (ADSCs) of mice and used in vivo imaging to track the local concentration of these vesicles following topical injection. We also evaluated the therapeutic effects of ADEVs on wound healing at different time intervals (4 days, 8 days, and 16 days). Our results indicated that ADEVs injected at concentration over 200 μg/mL persist in skin for more than 7 days. Notably, injection intervals of 4 days and 8 days significantly enhanced wound healing, whereas the 16-day interval did not show such benefits. Additionally, the skin scar tissues in the 4-day and 8-day groups exhibited normal skin structures and appendages, including hair follicles and sebaceous glands. In conclusion, the injection concentration and time intervals influence the outcomes of therapeutic effects of ADEVs under equal total dosages. ADEVs injected at concentration over 200 μg/mL harm the wound healing process with excessive accumulation and unexpected inflammation. Topical injection of ADEVs at a concentration of 50 μg/mL every 4 days or 100 μg/mL every 8 days promote wound healing and skin structure remodeling by regulating angiogenesis-related genes expression.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152223"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336037","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}