Biochemical and biophysical research communications最新文献

{"title":"Network pharmacology and experimental verification to explore the molecular mechanisms of Astragaloside IV against diabetic encephalopathy","authors":"Yong Wang ,&nbsp;Qianqian Yang ,&nbsp;Yanchao Lu ,&nbsp;Lei Jiang ,&nbsp;Rui Zhang ,&nbsp;Siyu Jiang ,&nbsp;Yuxuan Xu ,&nbsp;Shunjiang Xu ,&nbsp;Zuojun Geng","doi":"10.1016/j.bbrc.2025.151778","DOIUrl":"10.1016/j.bbrc.2025.151778","url":null,"abstract":"<div><h3>Purpose</h3><div>Diabetic encephalopathy (DE) is a neurological complication caused by diabetes mellitus, and its underlying mechanism has not been fully clarified. Astragaloside IV (AS-IV) has been demonstrated to have treatment effects on multiple neurologic diseases. The objective of this research is to explore the role and underlying mechanism of AS-IV in the treatment of DE, utilizing the methods of network pharmacology and experimental validation.</div></div><div><h3>Methods</h3><div>Multiple public databases were used to search for the targets of AS-IV. Gene Expression Omnibus (GEO) dataset (GSE16135) was analyzed to identify differentially expressed genes (DEGs) in DE. The Venn diagram was employed to determine the intersecting genes. These genes were considered potential therapeutic targets of AS-IV in DE and were annotated using bioinformatics techniques. Subsequently, a protein-protein interaction (PPI) network was constructed utilizing Cytoscape software to identify the core targets of action. Additionally, molecular docking was conducted to validate the binding affinity of AS-IV to the main targets. Finally, we validated the predictive outcomes of network pharmacology in a DE rat model induced by intraperitoneal injection of streptozotocin (STZ).</div></div><div><h3>Results</h3><div>Through the application of network pharmacology and bioinformatics analyses, we discovered the top two hub targets (EGFR and JAK2). Subsequent molecular docking analysis showed that AS-IV was precisely located within the binding sites of both EGFR and JAK2, with binding energies of −8.18 kJ/mol and −10.94 kJ/mol, respectively. Behavioral experiments demonstrated that the treated rats showed improvements in cognitive impairment. Following AS-IV treatment, there was a significant reduction in amyloid-β (Aβ) plaques deposition and neurofibrillary tangles in the hippocampal tissue of DE rats. Furthermore, TUNEL staining and Western blot analyses demonstrated that AS-IV suppressed neuronal apoptosis and inhibited the activation of the EGFR/JAK2/STAT3 signaling pathway.</div></div><div><h3>Conclusion</h3><div>These results demonstrated that the AS-IV has the potential to improve cognitive impairment in DE rats by mitigating neuronal apoptosis through the EGFR/JAK2/STAT3 signaling pathway, which provides important implications for the treatment of DE.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151778"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833203","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":"Vitamin K2 mitigates cognitive, and motor impairments induced by multiple surgery with anesthesia and analgesia in neonatal stage","authors":"Yu Hou ,&nbsp;Shuai Li ,&nbsp;Qi Hou ,&nbsp;Runjia Wang ,&nbsp;Xiyuan Xu ,&nbsp;Zhichao Li ,&nbsp;Linhui Ma ,&nbsp;Qidong Liu ,&nbsp;Yuan Shen ,&nbsp;Hui Zheng","doi":"10.1016/j.bbrc.2025.151784","DOIUrl":"10.1016/j.bbrc.2025.151784","url":null,"abstract":"<div><div>Anesthesia and analgesia are essential components for surgical procedures. While the neurotoxic effects of multiple anesthesia exposures during brain development are well established, the combined impact of multiple surgery with anesthesia and analgesia exposures on neurodevelopmental remains unknown. In this study, neonatal mice underwent multiple surgery with fentanyl and sevoflurane (MSFS) exposures on postnatal days 6, 8, and 10, resulting in attention deficit hyperactivity disorder (ADHD)-like hyperactivity, impulsive behavior, cognitive impairment, and fine motor dysfunction in adulthood. Additionally, MSFS exposures inhibited neurogenesis in the nucleus accumbens (NAc) by reducing neural stem cells (NSCs) proliferation and differentiation into neurons and astrocytes. Pre-administration of Vitamin K2 (VK2) 30 min before each MSFS procedure significantly mitigated the behavioral impairments and restored neurogenesis. RNA-sequencing revealed that MSFS treatment induced 75 up-regulated and 140 down-regulated differentially expressed genes (DEGs) in the NAc, while VK2 pre-administration resulted in 149 up-regulated and 56 down-regulated DEGs. Among these, 32 DEGs were down-regulated by MSFS but restored by VK2 and 12 DEGs were up-regulated by MSFS but down-regulated by VK2. To identify key regulatory genes modulated by VK2, we performed protein-protein interaction analysis using CytoHubba, which revealed 10 hub genes—DLGAP5, TPX2, KIF20B, PLK1, SGO1, GTSE1, ASPM, CDCA2, BUB1B, and NUSAP1—with critical roles in cell cycle, cell division and NSCs pathways. The expression of hub genes was validated by RT-qPCR and immunofluorescence staining. These findings suggest that MSFS-induces ADHD-like behaviors, cognitive impairment, fine motor dysfunction, impaired neurogenesis and altering genes expression involved in cell cycle, cell division and NSCs pathways, which are rescued by VK2. This study presents the clinically MSFS model for investigating neurodevelopmental toxicity and highlights VK2's potential as a neuroprotective agent in pediatric involving multiple surgery with anesthesia and analgesia.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"765 ","pages":"Article 151784"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859954","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 DNA repair factor ku80 binds and activates the adhesion receptor ELTD1/ADGRL4","authors":"Stefan Amisten ,&nbsp;Melinda Rezeli ,&nbsp;Mario Grossi ,&nbsp;Paulina Bryl-Gorecka ,&nbsp;Anton Håkansson ,&nbsp;Kristina Torngren ,&nbsp;György Marko-Varga ,&nbsp;David Erlinge ,&nbsp;Björn Olde","doi":"10.1016/j.bbrc.2025.151785","DOIUrl":"10.1016/j.bbrc.2025.151785","url":null,"abstract":"<div><div>We investigated the mRNA expression of G protein-coupled receptors (GPCRs) in cells from four human vascular beds: umbilical vein (HUVEC), microvasculature (MVEC), aorta (HAEC), and coronary artery (CAEC). Our study revealed that the orphan receptor ELTD1 (ADGRL4) was the most abundantly expressed GPCR mRNA in all four EC types. When recombinantly expressed in U87 cells, ELTD1 receptors activated canonical GPCR pathways, particularly the Gq pathway. Conditioned medium from U87 cells also activated ELTD1 in HEK293 cells, supporting the existence of an autocrine ELTD1-activating factor. Using affinity capture and mass spectrometry in combination with the label free xCelligence system, we identified the proteins ku80 and erythrocyte beta spectrin (SPTB) as ligands to ELTD1.</div><div>Ku80 demonstrated higher potency in activating ELTD1 than SPTB, thus leading us to focus on this protein. INCA-X, a functional antibody targeting the ku80/ku70 complex, and ELTD1 siRNA impaired endothelial tube formation in a similar manner, suggesting a common pathway. In a study cohort of myocardial infarction patients, high plasma levels of the extracellular domain of ELTD1 correlated (P &lt; 0.05) with high (&gt;2.9) cardiovascular flow reserve, thus indicating an association between ELTD1 and active angiogenesis and revascularization.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"764 ","pages":"Article 151785"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835147","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":"RPS15a knockdown impedes the progression of B-ALL by inducing p53-mediated nucleolar stress","authors":"Xinxin Li ,&nbsp;Sijia Di ,&nbsp;Fengze Nie ,&nbsp;Wenting Meng ,&nbsp;Siyong Huang","doi":"10.1016/j.bbrc.2025.151768","DOIUrl":"10.1016/j.bbrc.2025.151768","url":null,"abstract":"<div><div>Ribosome biogenesis is intricately linked to the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL), but the precise regulatory mechanisms remain to be elucidated. First of all, our study identify that RPS15a, the ribosomal small subunit structural protein, is significantly higher expressed in B-ALL patients, indicating a potential crucial role of RPS15a in modulating B-ALL progression. Next in importance, our findings found that RPS15a knockdown (KD) results in the impede of cell proliferation and cell cycle progression, while concurrently inducing apoptosis of B-ALL cells. Next, we used immunofluorescence staining of nucleolar proteins NPM1 and FBL to evaluate whether RPS15a KD-mediated abnormal nucleolar ribosome assembly triggers nucleolar stress. Our findings revealed that, in comparison to control B-ALL cells, RPS15a KD disrupted the localization of NPM1 and FBL within the nucleus, altered the normal architecture of the nucleolus, and induced nucleolar stress. Mechanistically, our study found that RPS15a KD impairs the ribosomal biogenesis by suppressing the synthesis and processing of ribosomal RNAs (rRNAs), including pre-rRNA, 18S rRNA, 28S rRNA, and 5.8S rRNA. Then, we observed that the depletion of RPS15a leads to the activation of p53 signaling, accompanied by an increase in the protein expression of p53 and p21, which are critical signals that induce nucleolar stress. Furthermore, our rescue experiment involving p53 KD found that the suppression of p53, following RPS15a KD, can alleviate ribosomal biogenesis, facilitate cell cycle progression and inhibit apoptosis. In conclusion, these findings suggest that RPS15a primarily regulates the progression of B-ALL by modulating p53 signaling-mediated nucleolar stress, thereby identifying RPS15a as a critical target for B-ALL treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151768"},"PeriodicalIF":2.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833202","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":"Targeting ALPPL2 with a novel CD89 bispecific antibody reprograms macrophages to enhance anti-tumor immunity","authors":"Lijun Xu ,&nbsp;Bowen Yang ,&nbsp;Junhan Zhang ,&nbsp;Shujian Liu ,&nbsp;Qi Zhang ,&nbsp;Longchao Ran ,&nbsp;Bingyu Li","doi":"10.1016/j.bbrc.2025.151761","DOIUrl":"10.1016/j.bbrc.2025.151761","url":null,"abstract":"<div><div>Immunotherapy holds promise for cancer treatment, but its efficacy in solid tumors is often limited by the immunosuppressive tumor microenvironment (TME). Macrophages, abundant within the TME, can be reprogrammed to elicit anti-tumor immunity. We developed a novel bispecific antibody, ALPPL2-CD89, to specifically target and activate macrophages within the tumor. The ALPPL2-CD89 bispecific antibody demonstrated high binding affinity to both targets and significantly enhanced macrophage-mediated phagocytosis of tumor cells. In vivo studies using human CD89 transgenic mice bearing ALPPL2-expressing tumors showed significant tumor growth inhibition. Analysis of the tumor microenvironment revealed that ALPPL2-CD89 treatment increased CD3⁺ and CD8⁺ T cell infiltration, and shifted tumor-associated macrophages toward a pro-inflammatory M1 phenotype. Our findings establish ALPPL2-CD89 as a promising therapeutic candidate that effectively reprograms the myeloid compartment to drive potent anti-tumor immunity against ALPPL2-positive malignancies.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151761"},"PeriodicalIF":2.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808677","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":"Tangeretin protects against Aβ1-42-induced toxicity and exploring mitochondria-lysosome interactions in HT22 cells","authors":"Ying He,&nbsp;Meng-Hui He,&nbsp;Tingting Jin,&nbsp;Siju-Li,&nbsp;Hua-Qiao Wang,&nbsp;Feng He","doi":"10.1016/j.bbrc.2025.151769","DOIUrl":"10.1016/j.bbrc.2025.151769","url":null,"abstract":"<div><div>Tangeretin, a flavonoid from <em>Citri Reticulatae</em> Pericarpium, is known for its neuroprotective effects, but the mechanisms are not fully understood. Alzheimer's disease, a leading neurodegenerative disorder, characterized by amyloid-beta (Aβ) accumulation, represents a significant therapeutic challenge. This study investigates the protective effects of tangeretin against Aβ1-42-induced neurotoxicity using HT22 cells and zebrafish larvae as experimental models. Tangeretin mitigated Aβ_1-42-induced cytotoxicity, as evidenced by enhanced cell viability and reduced apoptosis. Tangeretin treatment mitigated Aβ_1-42-induced cytotoxicity in HT22 cells, as evidenced by enhanced cell viability and reduced apoptosis. Mechanistically, tangeretin ameliorated mitochondrial dysfunction by reducing mitochondrial fragmentation, decreasing donut-shaped mitochondria, restoring mitochondrial membrane potential, and attenuating reactive oxygen species (ROS) production. Moreover, tangeretin modulated mitochondria-lysosome interactions by promoting mitophagy and normalizing the prolonged mitochondria-lysosome contact induced by Aβ_1-42. In zebrafish larvae, Aβ_1-42 exposure resulted in developmental malformations, including pericardial and yolk sac edema, elevated ROS levels, increased apoptosis, and impaired neurodevelopment. Tangeretin effectively counteracted these deficits, as revealed by live imaging, supporting its neuroprotective role observed in cellular models. Collectively, our study suggests that tangeretin may serve as a promising protective agent against Aβ_1-42-induced neurotoxicity.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151769"},"PeriodicalIF":2.5,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815864","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":"Correlation between persistent changes in ciliary dynamics in the FrA and depressive-like behavior","authors":"Rintaro Takahashi ,&nbsp;Akie Hamamoto ,&nbsp;Yumiko Saito,&nbsp;Aika Mizuno,&nbsp;Yuki Kobayashi","doi":"10.1016/j.bbrc.2025.151767","DOIUrl":"10.1016/j.bbrc.2025.151767","url":null,"abstract":"<div><div>Long-term stress contributes to depressive disorders, for which monoamine-based treatments are often inadequate. This study identifies neuronal primary cilia as critical regulators of stress-induced depressive-like behavior. In mice, short-term restraint stress (3 days) reduced cilia length and the proportion of cilia-bearing neurons within the frontal association cortex (FrA). These changes were reversible, with ciliary dynamics recovering after 2 weeks of normal housing, and depressive-like behavior being absent. In contrast, long-term stress (3 weeks) caused persistent cilia shortening and reduced prevalence in the FrA, accompanied by depressive-like behavior. Unlike for short-term stress, these changes persisted even after a 2-week recovery period. However, following a 10-week recovery period, both ciliary morphology and prevalence returned to control levels, along with a resolution of depressive-like behaviors. These findings strongly implicate ciliary dynamics as critical determinants of behavioral outcomes. We found that melanin-concentrating hormone receptor 1 (MCHR1) was predominantly expressed in FrA primary cilia, and restraint stress upregulated MCH expression. <em>Ex vivo</em> MCH treatment recapitulated the stress-induced ciliary shortening and reduced cilia prevalence in FrA brain slices. These findings suggest that MCH-MCHR1 signaling mediates ciliary changes under stress and that the failure to restore ciliary structure may be a key factor in the development of depressive-like behavior. Given the non-synaptic pathways of ciliary signaling, this pathway may represent a novel therapeutic target, especially for treatment-resistant depression.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151767"},"PeriodicalIF":2.5,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808605","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":"PVC nanoplastics impair cardiac function via lysosomal and mitochondrial dysfunction","authors":"Guoxia Liu ,&nbsp;Qimei Bao ,&nbsp;Chunkai Zhang ,&nbsp;Yuke Zhong ,&nbsp;Mingcong Deng ,&nbsp;Yixing Huang ,&nbsp;Zu Ye ,&nbsp;Ji Jing","doi":"10.1016/j.bbrc.2025.151736","DOIUrl":"10.1016/j.bbrc.2025.151736","url":null,"abstract":"<div><h3>Micro</h3><div>and nanoplastics (MNPs) are emerging environmental pollutants that pose a significant threat to human health, with traces found in cardiac tissues. While previous studies have indicated that MNPs can cantribute to cardiac dysfunction, there is limited systematic investigation into how MNPs exposure affects various organelles. This study focuses on polyvinyl chloride nanoparticles (PVC NPs), one of the most common and persistent plastic pollutants in the environment. Our findings reveal that PVC NPs engage in organelle-specific interactions, predominantly accumulating in the lysosomes and mitochondria of cardiomyocytes. This targeted accumulation results in substantial disruptions to lysosomal autophagic flux and mitochondrial energy metabolism. These results offer new insights into the organelle-specific mechanisms behind PVC NP-induced cardiotoxicity, highlighting the distinct risks associated with this widespread environmental contaminant.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151736"},"PeriodicalIF":2.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808690","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":"Integrative metabolic profiling of hypothalamus and skeletal muscle in a mouse model of cancer cachexia","authors":"Jae Yeon Choi ,&nbsp;Ye Jin Kim ,&nbsp;Jeong Seob Shin ,&nbsp;EunBi Choi ,&nbsp;Yuhyun Kim ,&nbsp;Min Gwan Kim ,&nbsp;Yang Tae Kim ,&nbsp;Byong Seo Park ,&nbsp;Jae Kwang Kim ,&nbsp;Jae Geun Kim","doi":"10.1016/j.bbrc.2025.151766","DOIUrl":"10.1016/j.bbrc.2025.151766","url":null,"abstract":"<div><div>Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive weight loss, muscle wasting, and systemic inflammation. Despite its clinical significance, the underlying mechanisms linking central and peripheral metabolic changes remain incompletely understood. In this study, we employed a murine model of cancer cachexia induced by intraperitoneal injection of Lewis lung carcinoma (LLC1) cells to investigate tissue-specific metabolic adaptations. Cachectic mice exhibited reduced food intake, body weight loss, impaired thermoregulation, and decreased energy expenditure. Metabolomic profiling of serum, skeletal muscle, and hypothalamus revealed distinct metabolic shifts, with increased fatty acid and ketone body utilization and altered amino acid metabolism. Notably, hypothalamic metabolite changes diverged from peripheral tissues, showing decreased neurotransmitter-related metabolites and enhanced lipid-based energy signatures. Gene expression analysis further confirmed upregulation of glycolysis- and lipid oxidation-related genes in both hypothalamus and muscle. These findings highlight coordinated yet compartmentalized metabolic remodeling in cancer cachexia and suggest that hypothalamic adaptations may play a central role in the systemic energy imbalance associated with cachexia progression.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151766"},"PeriodicalIF":2.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821362","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":"Quantifying renal lipid accumulation in obese murine models using Magnetic Resonance Imaging (MRI)","authors":"Jamie Lynne Lois Q. Balugo ,&nbsp;Joshua D. Samuels ,&nbsp;Joshua L. Milstein ,&nbsp;Maurits A. Jansen ,&nbsp;Thurl E. Harris ,&nbsp;Silas A. Culver","doi":"10.1016/j.bbrc.2025.151765","DOIUrl":"10.1016/j.bbrc.2025.151765","url":null,"abstract":"<div><div>Renal cortical lipid content is increased in obesity and contributes to obesity-related kidney dysfunction. Studying this phenomenon requires reliable tools to quantitate renal cortical lipid in preclinical models. However, most current preclinical methods require euthanizing the model. MRI has been used to measure lipid content in other organ systems but, to our knowledge, has not been employed in quantifying kidney lipid in mice. Eleven-week old male C57BL/6 mice were fed either standard chow (ND) (12 % fat) or high fat diet (HFD) (45 % fat) for 12 weeks. At the end of this period, a 9.4 T Bruker MRI was utilized to perform fat-water separation imaging based on the Dixon method. These images were utilized to calculate a proton-density fat fraction for regions of interest within the renal cortex. For validation, frozen kidney sections underwent immunofluorescent LipidSpot™ staining for quantitation of lipid droplet area. After 12 weeks on diet, the average body weight of HFD fed mice was 34.63g compared to 27.84g in ND controls (p &lt; 0.001). Consistent with prior studies, MRI demonstrated increased hepatic fat content of 13.34 % in HFD fed mice compared to 8.3 % in ND controls (p &lt; 0.05). Renal cortical lipid measured by MRI averaged 7.35 % in HFD fed mice compared to 4.75 % in ND controls (p &lt; 0.05). On histologic analysis, HFD fed mice had a ratio of lipid droplet area to DAPI of 0.866 compared to 0.221 in ND fed mice (p &lt; 0.05). These results demonstrate that MRI can be used effectively to measure changes in renal cortical lipid content in mice.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151765"},"PeriodicalIF":2.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808678","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}