Biochemistry and Biophysics Reports最新文献

{"title":"β-Hydroxybutyrate promotes chemoresistance and proliferation in breast cancer cells","authors":"Milad Mashinchian ,&nbsp;Somayeh Vandghanooni ,&nbsp;Amir Reza Karamibonari ,&nbsp;Morteza Eskandani","doi":"10.1016/j.bbrep.2025.102217","DOIUrl":"10.1016/j.bbrep.2025.102217","url":null,"abstract":"<div><div>Breast cancer is the most prevalent cancer among women, posing significant challenges due to its heterogeneity. Recent studies suggest that the ketogenic diet (KD) may enhance chemotherapy efficacy by modulating cancer cell metabolism, particularly through the elevation of ketone bodies like β-hydroxybutyrate (BHB). This study investigates the effects of BHB on breast cancer cells using both 2D and 3D culture models, focusing on its role in developing resistance to fluorouracil (5-FU). We utilized CF41.Mg canine mammary gland cancer cells and MCF7 human breast cancer cells to assess BHB's effects as a pre-treatment and post-treatment under varying glucose conditions. The findings indicated that BHB notably increased cell viability, proliferation, and migration. Pre-treatment resulted in a 52.94 % increase in viability for CF41.Mg cells and a 54.73 % increase for MCF7 cells after 48 h, compared to treatment with 5-FU alone. This enhancement persisted at 72 h, indicating BHB's potential to promote resistance to 5-FU. In 3D spheroid models, which better mimic the tumor microenvironment, BHB pre-treatment significantly increased spheroid size and conferred resistance to 5-FU in both cell lines. Additionally, BHB pre-treatment elevated the expression of proliferation markers such as Ki-67 and tumorigenic markers like MUC-1 (Mucin 1), while showing no significant impact on mesenchymal markers like N-cadherin and vimentin. These findings suggest that BHB significantly increases resistance to 5-FU, indicating that BHB may enable cancer cells to evade chemotherapy-induced stress. Our findings raise important questions about the potential dual role of BHB and KD in promoting cancer cell survival while potentially complicating treatment outcomes.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102217"},"PeriodicalIF":2.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908062","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":"Evaluating the effect of the mitochondrial alternative peptide MTALTND4 on gene expression","authors":"Ludovic Nadeau-Lachance,&nbsp;Thierry Choquette,&nbsp;Hajar Hosseini Khorami,&nbsp;Annie Angers,&nbsp;Sophie Breton","doi":"10.1016/j.bbrep.2025.102223","DOIUrl":"10.1016/j.bbrep.2025.102223","url":null,"abstract":"<div><div>• This is a preliminary study exploring the effect of the mitochondrial alternative peptide MTALTND4 on gene expression in two different culture media using microarrays, RNA-seq and RT-qPCR.</div><div>• Microarrays in MiR05 medium suggest that exogenous treatment with MTALTND4 may alter gene expression and that responsive genes are mostly related to cell metabolism.</div><div>• Conversely, RNA-seq in DMEM low glucose suggests that MTALTND4 has a negligible impact on gene expression.</div><div>• RT-qPCR in MiR05 or DMEM low glucose indicates that the culture media affects gene regulation.</div><div>• This study emphasizes the importance of employing diverse approaches when examining the physiological effects on cells and the need to carefully select the appropriate culture media to interpret cellular responses and expression data accurately.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102223"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908060","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":"Inhibition of PI3K/AKT/mTOR signaling enhances autophagy in HL-60 acute myeloid leukemia cells: An integrative bioinformatic and in vitro study","authors":"Mohammad Malekan ,&nbsp;Armin Dozandeh-Jouybari ,&nbsp;Nazanin Joudaki ,&nbsp;Mehdi Ahangari ,&nbsp;Reza Valadan ,&nbsp;Hossein Asgarian-Omran ,&nbsp;Saeid Taghiloo","doi":"10.1016/j.bbrep.2025.102220","DOIUrl":"10.1016/j.bbrep.2025.102220","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) involves uncontrolled proliferation of myeloid progenitor cells and carries a poor prognosis. The PI3K/AKT/mTOR pathway plays a key role in AML pathogenesis by regulating cancer cell proliferation and survival. This study investigates the effects of inhibiting the PI3K/AKT/mTOR pathway on autophagy in AML cell lines, aiming to support targeted therapy development that modulates autophagy.</div></div><div><h3>Methods</h3><div>Gene expression and prognostic significance of PI3K/AKT/mTOR and autophagy-related genes in AML were evaluated using Enricher, GEPIA2, and Human Protein Atlas databases. HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, selective PI3K, AKT, and mTOR inhibitors, either individually or in combination. Autophagy gene expression (<em>Beclin-1, LC3-II, Atg5, ATG7</em>) was assessed by Real-time PCR.</div></div><div><h3>Result</h3><div>Bioinformatic analysis revealed that autophagy genes are associated with PI3K/AKT/mTOR pathway in AML. We observed that HL-60 AML cell lines treated with PI3K/AKT/mTOR inhibitors exhibited significant enhancement in the expression of key autophagy-related genes, including <em>Beclin-1</em>, <em>LC3-II</em>, <em>ATG5</em>, and <em>ATG7</em>, particularly with combination treatment.</div></div><div><h3>Conclusion</h3><div>PI3K/AKT/mTOR inhibitors significantly induce autophagy-related gene expression in AML cells. These findings support combining such inhibitors with autophagy modulators as a potential strategy to improve AML treatment outcomes.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102220"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908063","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 ontogeny of circadian clock gene expression during mouse fetal development","authors":"Daniel L. Stanton ,&nbsp;Linkai Zhu ,&nbsp;Peter J. Hansen","doi":"10.1016/j.bbrep.2025.102216","DOIUrl":"10.1016/j.bbrep.2025.102216","url":null,"abstract":"<div><div>The circadian clock in the suprachiasmatic nucleus and peripheral tissues functions to regulate key physiological and cellular systems in a cycle approximating 24 h. Understanding the ontogeny of the circadian clock mechanism during mammalian development is incomplete. Accordingly, we used the mouse as a model and a previously published RNAseq dataset to determine when expression of core genes regulating the circadian clock increase in transcript abundance in fetal and postnatal brain, heart, liver, and kidney. Transcripts for all six core genes examined (<em>Clock, Bmal1, Per1, Per2, Cry1</em>, and <em>Cry2</em>) were identified in all tissues and time points. For brain, there was a small increase in <em>Clock</em> at E13.5 and a larger increase at E18.5. Similarly, <em>Bmal1</em> transcript abundance increased slightly at E14.5 and to a greater degree at E17.5, <em>Per2</em> increased slightly at E15.5 and remained constant until after birth and <em>Cry2</em> increased slightly at E18.5. For liver, transcript abundance of most genes increased at the end of gestation, with increases observed for <em>Clock</em> at E18.5, and for <em>Bmal1</em>, <em>Per2</em>, and <em>Cry2</em> at E17.5. The genes whose expression increased before birth in heart was <em>Clock</em> (at E18.5), and <em>Per2</em> (at E15.5) and the genes whose expression increased before birth in kidney were <em>Clock</em> (E18.5), <em>Bmal1</em> (E15.5) and <em>Per1</em> (P18.5). For all tissues, there were further increases in transcript abundance for most genes in the postnatal period with the exception of <em>Cry1</em> (all tissues) and <em>Per1</em> (liver and kidney)<em>.</em> Results support the idea that the organization of the molecular clock is more advanced for the fetal brain and liver than for fetal heart and kidney. Furthermore, based on changes in gene expression, components of the molecular clock continued to mature after birth.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102216"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902852","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":"Identification of a piwi1 homologue gene in the orange-spotted grouper (Epinephelus coioides) and its expression pattern in the germ cell lineage","authors":"Ling Qu ,&nbsp;Kunlun Xiang","doi":"10.1016/j.bbrep.2025.102188","DOIUrl":"10.1016/j.bbrep.2025.102188","url":null,"abstract":"<div><div>The protogynous orange-spotted grouper (<em>Epinephelus coioides</em>), a sequentially hermaphroditic teleost, relies on dynamic regulation of germ cell development and sex reversal mechanisms to achieve reproductive plasticity. The <em>piwi</em> gene family, pivotal for germ cell development and transposon silencing across metazoans, remains poorly characterized in hermaphroditic species. Here, we investigate <em>Ecpiwi1</em>, a <em>piwi1</em> homologue in the orange-spotted grouper (<em>E</em>. <em>coioides</em>), to elucidate its role in germ cell fate determination and sex reversal. We cloned a 3084-bp Ecpiwi1 cDNA encoding an 855-amino-acid protein containing conserved PAZ and PIWI domains, phylogenetically clustering with vertebrate Piwi proteins. Real-time PCR showed that the expression level of <em>Ecpiwi1</em> mRNA increases during sex reversal, transitioning from ovary to testis. Spatial expression analysis by in situ hybridization and immunohistochemistry demonstrated <em>Ecpiwi1</em> localization to oogonia, previtellogenic oocytes, and spermatogonia-spermatocyte transition zones. During natural and 17α-methyltestosterone (MT)-induced sex reversal, <em>Ecpiwi1</em> mRNA exhibited progressive upregulation during sex reversal. Notably, MT-treated gonads showed identical <em>Ecpiwi1</em> expression dynamics and subcellular localization patterns compared to natural sex change, validating the MT induction model. These findings establish Ecpiwi1 as a germline-specific regulator coordinating oogenesis, spermatogenesis, and sex reversal in protogynous hermaphrodites. The conserved expression patterns under exogenous androgen induction position <em>Ecpiwi1</em> as a robust molecular marker for teleost germline stem cell studies and advance our understanding of reproductive plasticity in hermaphroditic teleosts.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102188"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902851","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":"Houttuynia cordata triggers type I interferon signaling to promote host defense against Acinetobacter baumannii infection via mTORC1 activation","authors":"Qingqing Xie ,&nbsp;Lele Liu ,&nbsp;Ziwei Zhang ,&nbsp;Yanfeng Li ,&nbsp;Xiaopeng Qi ,&nbsp;Tao Xu ,&nbsp;Xiaoqing Xu","doi":"10.1016/j.bbrep.2025.102213","DOIUrl":"10.1016/j.bbrep.2025.102213","url":null,"abstract":"<div><div>Multidrug-resistant <em>Acinetobacter baumannii</em>, a prevalent opportunistic pathogen in hospitals, presents a substantial risk to immunocompromised patients, triggering life-threatening conditions including pneumonia, bacteremia, and sepsis, which can be fatal. Therefore, it is urgent to develop new therapeutic strategies to combat and eradicate multidrug-resistant <em>A. baumannii</em> infection. Our finding reveals that <em>Houttuynia cordata</em> promotes the mice treated with 5-fluorouracil (5-FU) to defend against multidrug-resistant <em>A. baumannii</em> infection via the mTORC1-IFN-I signaling pathway. Mechanistically, <em>Houttuynia cordata</em> triggers mTORC1 activation through the phosphorylation of p38 MAPK, and mTORC1 is required for the subsequent activation of IFN-I signaling pathways in response to <em>Houttuynia cordata</em> treatment. <em>In vivo</em> studies have demonstrated that <em>Houttuynia cordata</em> enhances the clearance of <em>A. baumannii</em> in mice subjected to 5-FU chemotherapy, with this effect being mediated through the mTORC1 signaling pathway. Our study provides insight into the therapeutic intervention of enhancing IFN-I signaling and boosting host defense against bacterial infections via the administration of <em>Houttuynia cordata</em>.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102213"},"PeriodicalIF":2.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896162","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":"Early pharmacological blockade of the CXCL12-CXCR4 axis attenuates vertebral hypercalcification in a zebrafish model of pseudoxanthoma elasticum.","authors":"Jianjian Sun, Jichang Huang, Renjie Zhang, Shubin Zhang, Tao P Zhong, Ping Zhu","doi":"10.1016/j.bbrep.2025.102204","DOIUrl":"10.1016/j.bbrep.2025.102204","url":null,"abstract":"<p><p>Pseudoxanthoma elasticum (PXE), caused by pathogenic variants in <i>ABCC6</i>, is characterized by pathological ectopic calcification with poorly understood mechanisms and no effective therapies. To address this, we developed the first zebrafish model of human PXE by introducing the pathogenic <i>ABCC6</i> point mutation (<i>abcc6a</i> ^{<i>R1463C/R1463C</i>} , F2 generation) using the highly efficient zhyA3A-CBE5 cytosine base editor. Three mutant types (Type1-Type3, T1-T3) stratified by calcification severity, exhibited reduced levels of the calcification inhibitors vitamin K1 (VK1) and carboxylated matrix Gla protein (cMGP), which were inversely correlated with the severity of calcification. Vertebral transcriptomics revealed dysregulated pathways related to ossification, bone remodeling-associated extracellular matrix (ECM), and immune responses, with the CXCL12-CXCR4 axis identified as a pivotal signaling hub. Early pharmacological blockade of CXCR4 using AMD3100 initiated at 5 days post-fertilization (dpf), significantly attenuated hypercalcification, whereas late intervention (from 1 month post-fertilization, mpf) demonstrated minimal efficacy. Notably, dual-target therapy combining VK1 and AMD3100 synergistically reduced hypercalcification in T3 mutants, surpassing the effects of either monotherapy. This synergy indicates functional crosstalk between vitamin K metabolism and CXCL12-CXCR4 signaling. These findings identify the CXCL12-CXCR4 axis as a therapeutic target for ectopic calcification and propose a novel dual-target strategy for PXE treatment.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"102204"},"PeriodicalIF":2.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940738","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}

{"title":"In vitro evidence of HER2-selective cytotoxicity by scFv(Herceptin)-PE-STXA immunotoxin in gastric cancer cells.","authors":"Hamid Sedighian, Arash Abdi, Zoleikha Goleij, Mahdi Fasihi-Ramandi, Abbas Ali Imani Fooladi","doi":"10.1016/j.bbrep.2025.102218","DOIUrl":"10.1016/j.bbrep.2025.102218","url":null,"abstract":"<p><p>The delivery of therapeutic agents in a targeted manner shows great potential for improving the degree of efficacy in cancer therapies by minimizing harm for normal tissues and reducing treatment-related complications. Among patients with gastric cancer, the HER2 receptor is expressed in approximately 10-30 % of cases. The scFv(Herceptin)-PE-STXA was cloned into the pET28a vector, followed by protein expression and purification. HEK-293 cells served as the control (HER2-negative), while NCI-N87 cells were utilized as the gastric cancer cells (HER2-positive). The cells were subjected to exposure different concentrations (35 and 50 μg/mL) of immunotoxin, after which growth was assessed using the MTT test. The capability of scFv(Herceptin)-PE-STXA to induce apoptotic pathway in NCI-N87 and HEK-293 cells was estimated through flow cytometry. Furthermore, the affinity for binding the IT, lactate dehydrogenase release, and the measurement of apoptosis pathway enzymes (caspase-9 and caspase-3 activities) were also conducted. The outcomes demonstrated that cytotoxic effects occurred in NCI-N87 cells with a dose-proportional manner approach, whereas no such impact was seen in HEK-293(P < 0.001). Flow cytometry analysis of NCI-N87 cells treated with scFv(Herceptin)-PE-STXA revealed a significant increase in apoptotic rate at dose of 35 and 50 μg/mL (55.6 % and 74.2 %). Additional analysis showed that exposing HER2-expressing NCI-N87 cells to the scFv(Herceptin)-PE-STXA caused a notable to enhance in apoptotic caspases activity (3 and 9) (P < 0.001). Results of our study indicated that the scFv(Herceptin)-PE-STXA induces apoptosis in the NCI-N87 cell line derived from gastric cancer. This study emphasizes the potential of scFv(Herceptin)-PE-STXA to specifically target HER2-expressing cancer cells.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"102218"},"PeriodicalIF":2.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038932","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}

{"title":"IMDM-20 enhances neutrophilic features during 1.3 % DMSO-mediated differentiation of HL-60 cells.","authors":"Jorge Andrés Cázares-Preciado, José Antonio Cruz-Cárdenas, Alejandra López-Arredondo, Marco V Gallardo-Camarena, Marion E G Brunck","doi":"10.1016/j.bbrep.2025.102215","DOIUrl":"10.1016/j.bbrep.2025.102215","url":null,"abstract":"<p><p>The promyelocytic HL-60 cell line can be differentiated toward neutrophil-like cells and has been historically used as a surrogate to study human neutrophil biology <i>in vitro</i>. Multiple differentiation protocols have been reported to generate neutrophil-like HL-60 cells, with limited consideration of how methodological variations might influence cell identity and functions. Here, we conducted a systematic search of the PubMed database, to investigate the current heterogeneity in published protocols used to differentiate HL-60 towards neutrophil-like cells. Research articles published in English between January 9th^, 2020, and January 9th^, 2025, were identified using the key words \"neutrophil-like cell\" and \"HL-60\". Metadata of included research papers were charted and analyzed to evaluate the most reported HL-60 cells culture protocols. A total of 71 studies published in 5 years employed 41 distinct protocols. The 3 most prevalent conditions to maintain HL-60 cells were IMDM with 20 % FBS (IMDM-20), DMEM with 10 % FBS (DMEM-10), and RPMI-1640 with 10 % FBS (RPMI-10). Over 90 % of protocols applied 1-1.57 % DMSO as differentiating agent to produce neutrophil-like cells. In the laboratory, we compared the 3 most common culture media applied during neutrophil-like cell differentiation with 1.3 % DMSO over 5 and 7 days. Using IMDM-20 led to the highest proliferation rate and cell yield during differentiation. Neutrophil-like cells produced in IMDM-20 and RPMI-10 exhibited significantly higher proportions of CD15⁺CD11b⁺ cells, and significantly higher bacterial clearance compared to DMEM-10. Culture media did not affect phagocytosis, but using RPMI-10 over 5 days led to significantly higher ability to produce ROS. IMDM-20 produced significantly more IL-6 and IL-1β in culture supernatant following stimulation with opsonized <i>E. coli</i>. Overall, the results support the use of IMDM-20 with 1.3 % DMSO to differentiate HL-60 to study neutrophil biology <i>in vitro</i>.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"102215"},"PeriodicalIF":2.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940732","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}

{"title":"Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy.","authors":"Xiaonan Zhang, Yan Liu, Mengxue Xia, Manwen Yang, Yingjie Wu, Fang Zhang","doi":"10.1016/j.bbrep.2025.102182","DOIUrl":"10.1016/j.bbrep.2025.102182","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR), a leading cause of blindness among working-age adults, lacks targeted therapies besides glucose management. Early retinal lesions are linked to serum metabolites, but the underlying peripheral regulatory networks is unclear.</p><p><strong>Methods: </strong>We first established a streptozotocin (STZ)-induced mouse model of early DR exhibiting retinal inflammation characteristics. This study employed an integrative approach, combining retinal and serum transcriptomic and metabolomic profiles with genome-wide association study (GWAS) data, to identify peripheral metabolites potentially linking early retinal lesions.</p><p><strong>Results: </strong>STZ-induced mice exhibited retinal inflammation and metabolic dysregulation. Metabolites including glucose, sorbitol, and mannitol were altered in both serum and retina, implicating their potential involvement in retinal inflammation. Utilizing GWAS data of diabetic patients, we further explore the potential the upstream regulation of shared metabolites and their peripheral pathways potentially instigating early retinal inflammation through metabolite-related genes correlated with single nucleotide polymorphisms. Key enzyme genes including HK1, HKDC1, AKR1B1 in hyperglycemic pathway, CEL and HMGCR in cholesterol pathway, and ACSL1, PPT2 in palmitic acid pathway, may connect the metabolic network of hyperglycemia, hyperfructosemia and disrupted lipid metabolism to retinopathy.</p><p><strong>Conclusion: </strong>This study elucidates the upstream regulatory network of peripheral serum metabolites associated with early retinal lesions. Specifically, the SNPs in key peripheral enzyme genes may exert remote effects on retinal inflammation in DR. This finding provides insights into the systemic metabolic management and offering peripheral precise early detection and treatment.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"102182"},"PeriodicalIF":2.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038960","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}