Archives of biochemistry and biophysics最新文献

{"title":"Exosomes from isobavachin-modified bone marrow mesenchymal stem cells promote osteoblast proliferation and alleviate osteoporosis by targeting the miR-127-3p/KIF3B/Wnt/β-catenin pathway","authors":"Yu Ning ,&nbsp;Luanning Li ,&nbsp;Xiangzhong Liu ,&nbsp;Haijia Xu ,&nbsp;Wei Wang","doi":"10.1016/j.abb.2025.110713","DOIUrl":"10.1016/j.abb.2025.110713","url":null,"abstract":"<div><h3>Background</h3><div>Mesenchymal stem cell-derived exosomes (MSC-exosome), a promising cell-free strategy, show attractive applications in the treatment of osteoporosis. Pretreatment of MSCs before application can effectively improve the therapeutic efficacy of MSC-exosomes. Our study investigated the effects of exosomes from isobavachin <strong>(</strong>IBA)-pretreated human bone marrow-derived MSCs (hBMSC^IBA-exosomes) on osteoporosis progression and further unveil the underlying molecular mechanism.</div><div>Methods: hBMSCs were treated with IBA alone, transfected with miR-NC/miR-127-3p alone, or pre-treated with IBA and then transfected with NC inhibitor/miR-inhibitor, followed by the collection of exosomes. Human hFOB1.19 osteoblasts were co-cultured with hBMSC-exosomes, and osteoblast proliferation and differentiation were detected. The target gene of miR-127-3p was predicted using bioinformatic analysis and validated by dual-luciferase reporter assay. The KIF3B silencing vector (sh-KIF3B) and the Wnt/β-catenin pathway agonist LiCl were used to respectively validate the involvement of KIF3B and the Wnt/β-catenin pathway in the effects of exosomal miR-127-3p from IBA-treated hBMSCs on osteoblast proliferation and differentiation. Ovariectomy (OVX)-induced rat models of osteoporosis were injected with hBMSC^IBA-exosomes. Their anti-osteoporotic and pro-osteogenic effects <em>in vivo</em> were confirmed through micro-CT analysis, histological examination, and detection of osteogenesis markers.</div></div><div><h3>Results</h3><div>IBA enhanced the promotive effects of hBMSC-exosomes on osteoblast proliferation and differentiation. IBA pretreatment upregulated miR-127-3p expression in hBMSCs and derived exosomes. Overexpressing exosomal miR-127-3p facilitated while downregulating exosomal miR-127-3p suppressed osteoblast proliferation and differentiation Mechanistically, miR-127-3p targeted KIF3B to facilitate the Wnt/β-catenin pathway. KIF3B silencing or LiCl pretreatment reversed the effects of exosomal miR-127-3p knockdown on osteoblast proliferation and differentiation. Additionally, IBA enhanced the anti-osteoporotic and pro-osteogenic effects of hBMSC-exosomes in osteoporosis rat models. However, inhibition of exosomal miR-127-3p abrogated the beneficial effects of hBMSC^IBA-exosomes in osteoporotic rats.</div></div><div><h3>Conclusion</h3><div>Exosomes derived from IBA-pretreated hBMSCs markedly stimulate osteogenesis and ameliorate osteoporosis by delivering miR-127-3p, which inhibits KIF3B and activates the Wnt/β-catenin pathway. Our results reveal the potential of IBA in improving the efficacy of hBMSC-exosomes in the treatment of osteoporosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"777 ","pages":"Article 110713"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826667","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":"NAG-1/GDF15 modulates hepcidin expression through STAT3 and SMAD pathways","authors":"Pattawika Lertpatipanpong ,&nbsp;Chutwadee Krisanapun ,&nbsp;Kanokkan Boonruang ,&nbsp;Yong Jin Jung ,&nbsp;Seung Joon Baek","doi":"10.1016/j.abb.2025.110724","DOIUrl":"10.1016/j.abb.2025.110724","url":null,"abstract":"<div><div>Hepcidin, a liver-derived hormone, is a central regulator of iron homeostasis and a key contributor to anemia of inflammation (AI). This study investigates the regulatory role of NAG-1 (Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1; also known as GDF15) in modulating hepcidin expression. In NAG-1 transgenic mice, elevated circulating NAG-1 was associated with markedly reduced hepatic hepcidin expression, demonstrating an in vivo role for NAG-1 in hepcidin suppression. To further dissect the mechanism, we established HepG2 cell lines stably overexpressing either NAG-1 WT (wild type), which produces both pro- and mature forms, or the R193A mutant, which secretes only the pro-form. Both WT and R193A significantly suppressed IL-6– and BMP6-induced hepcidin expression, with the mutant showing slightly stronger inhibition in some assays. Mechanistically, NAG-1 inhibited both the JAK/STAT3 and BMP6/SMAD pathways by reducing STAT3 activation and Smad1/5/9 phosphorylation, thereby limiting their recruitment to the HAMP promoter. Furthermore, co-expression of NAG-1 with the transcriptional corepressor SMILE produced an additive suppression of hepcidin, through enhanced inhibition of STAT3 signaling, despite only weak physical interaction between the two proteins. Together, these findings establish NAG-1 as a negative regulator of hepcidin transcription and demonstrate that the pro-form retains substantial biological activity within cells, providing new therapeutic insights into the management of anemia of inflammation through modulation of iron metabolism.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"777 ","pages":"Article 110724"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882244","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":"(R)-bambuterol ameliorates DSS-induced colitis in mice fed a high-fat diet via modulating immune response, intestinal barrier integrity, gut microbiota, and metabolomic profiles","authors":"Liangjun Deng ,&nbsp;Le Tian ,&nbsp;Dan Su ,&nbsp;Yipeng Li ,&nbsp;Shidong Zhang ,&nbsp;Shanping Wang ,&nbsp;Zhihua Liu","doi":"10.1016/j.abb.2026.110734","DOIUrl":"10.1016/j.abb.2026.110734","url":null,"abstract":"<div><div>The consumption of a high-fat diet is currently thought to be closely related to the onset of ulcerative colitis. (R)-bambuterol ((R)-BMB) has anti-inflammatory effects in the treatment of respiratory system related diseases. However, the therapeutic effect of (R)-BMB against in high-fat diet-related colitis remain undocumented. Therefore, in this study, the alleviation effect of (R)-BMB in mice with dextran sulfate sodium (DSS)-induced colitis fed a high-fat diet and its potential mechanism was explored. The results demonstrated that (R)-BMB markedly ameliorated the symptoms of colitis, such as body weight loss, spleen swelling and colon shortening. Moreover, (R)-BMB obviously mitigated the levels of inflammatory cytokines. Further research exhibited that (R)-BMB inhibited the NF-κB signaling pathway, regulated the balance of Th17 and Treg cells, elevated activated the Nrf-2/HO-1 signaling pathway, and increased the expression of related to tight junction proteins to increase the integrity of the intestinal barrier. In addition, 16S rDNA sequencing results indicated that (R)-BMB regulated the structure of the intestinal microbiome and relieved imbalances in this microbiome, and non-targeted metabolomics analysis revealed that (R)-BMB reversed the metabolic changes in mice with colitis fed a high-fat diet. In summary, these results indicate that (R)-BMB can serve as a novel alternative strategy for treating colitis in the context of high-fat diet consumption.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"777 ","pages":"Article 110734"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973752","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":"Incorporation of unnatural amino acid into human acidic fibroblast growth factor 1 (FGF1) protein with increased thermal, chemical stability and enhanced bioactivity","authors":"Reyhaneh Tavousi Tabatabaei,&nbsp;Zeina Alraawi,&nbsp;Chenguang Fan,&nbsp;Paul Adams,&nbsp;Thallapuranam Krishnaswamy Suresh Kumar","doi":"10.1016/j.abb.2025.110706","DOIUrl":"10.1016/j.abb.2025.110706","url":null,"abstract":"<div><div>Human acidic fibroblast growth factor 1 (hFGF1) is a critical regulator of cell proliferation, angiogenesis, and tissue regeneration, making it a promising candidate for therapeutic applications in chronic wound healing. However, its clinical utility has been significantly limited by inherent biophysical liabilities, including low thermal stability (Tm ∼42 °C), high susceptibility to proteolytic degradation—particularly cleavage at Arg136 by thrombin—and dependence on heparin for structural integrity and receptor activation. These limitations are especially problematic in diabetic wounds, where elevated protease levels, reduced vascularization, and chronic inflammation compromise the healing environment and degrade native growth factors.</div><div>In this study, we engineered a structurally stabilized hFGF1 variant (R136sY) through the site-specific incorporation of sulfotyrosine at position 136, aimed at reversing the positive charge in the heparin-binding pocket to enhance resistance to proteases and improve functional stability. Biophysical characterization confirmed that the R136sY mutant preserved the native β-trefoil architecture while displaying significantly improved thermostability (Tm = 54 °C, a 12 °C increase over wild type hFGF1), chemical stability (<em>Cm</em> = 2.8 M urea vs. 1.5 M for wild type hFGF1), and structural compactness, as evidenced by reduced ANS binding and limited trypsin digestion profiles. Notably, after 40 min of exposure to trypsin, more than 90 % of R136sY remained intact, compared to less than 10 % of hFGF1.</div><div>Functionally, R136sY promoted significantly enhanced mitogenic activity in NIH 3T3 fibroblasts at lower concentrations (2–29 ng/mL, p &lt; 0.05) even in the absence of heparin, indicating improved potency relative to hFGF1 (Kerr et al., 2019) 66. has direct translational implications, as it simplifies formulation requirements and ensures activity in protease-rich environments such as chronic diabetic wounds.</div><div>Collectively, these findings demonstrate that the R136sY mutant confers critical biophysical and functional improvements by stabilizing the protein's conformation and reducing proteolytic vulnerability. These mechanistic insights provide valuable design principles for engineering second-generation FGF1 analogs optimized for chronic wound care. Specifically, they support the development of protease-resistant, thermostable, and heparin-independent FGF1 variants capable of maintaining biological activity in the harsh microenvironments characteristic of diabetic ulcers—thereby addressing one of the major limitations in current growth factor-based therapies.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110706"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802974","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":"Development and In vitro kinetic evaluation of PEG-chitosan biohybrid micelles loading CBD with bile acid/quercetin as surface modifiers for colon cancer therapy","authors":"Qurat Ul Ain Haidery ,&nbsp;Bo Han ,&nbsp;Xingyuan Ma ,&nbsp;Wenyun Zheng","doi":"10.1016/j.abb.2025.110711","DOIUrl":"10.1016/j.abb.2025.110711","url":null,"abstract":"<div><div>Treatment for colon cancer is an intricate endeavor that demands innovative strategies for increasing the efficacy while lowering mortality and adverse effects. This study investigates the viability of delivering CBD to colon cancer cells by employing biohybrid micelles for oral delivery. These micelles are made of polyethylene glycol (PEG) and chitosan with bile acid and quercetin on the surface to synergistically increase CBD's anticancer benefits at lower doses and with fewer adverse effects. Chitosan's mucoadhesion and penetration facilitate PEG controlled release. The morphology, crystalline nature, stability, encapsulation efficiency (EE = 77.3 % ± 2 %), and composition of the biohybrid micelles are examined by using SEM, TEM, XRD, HPLC, FTIR, and TGA. IC50 values in μM (HCT116: 9.871 ± 0.244, HT29: 17.110 ± 2.515, Caco-2: 20.023 ± 2.685), colon cancer cell lines showed treatment with these micelles reduced cell survival in a dose-dependent manner relative to free CBD. Apoptosis investigations revealed increased caspase-3/7 activity by biohybrid micelles along with upregulation of Bax expression and downregulation of Bcl-2 expression confirmed by ELISA. Efficiency of component release from biohybrid micelles at varying pH levels is assessed after 72 h at pH 1.2, 6.8, and 7.4 (n ≥ 3). Drug release rates: Bile acid surpasses quercetin, which exceeds CBD (p &lt; 0.05). This innovative drug delivery technique improves CBD colon cancer treatment by combining controlled release with quercetin synergy, laying a foundation for clinical trials.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110711"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809281","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":"circCacna1c modulates osteogenic differentiation of BMSCs via miR-7669-3p/Ciart axis in osteoporosis","authors":"Zhipeng Chen ,&nbsp;Yan Li ,&nbsp;Bailing Chen","doi":"10.1016/j.abb.2025.110678","DOIUrl":"10.1016/j.abb.2025.110678","url":null,"abstract":"<div><div>Osteoporosis is a prevalent disorder characterized by reduced bone mass and deterioration of bone microstructure, leading to an increased risk of fractures. The osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) plays a critical role in bone formation. Circular RNAs (circRNAs) have been implicated in various diseases, including osteoporosis, by modulating gene expression. This study explores the role of circCacna1c in osteogenic differentiation and its potential as a therapeutic target for osteoporosis. CircCacna1c expression was downregulated in OVX mice and upregulated during osteogenic differentiation of BMSCs. Overexpression of circCacna1c promoted osteogenesis by increasing key osteogenic markers, such as <em>Runx2</em>, <em>Ocn</em>, and <em>Alp</em>. CircCacna1c was found to act as a molecular sponge for miR-7669-3p, which targets <em>Ciart</em>, enhancing its expression. The miR-7669-3p/<em>Ciart</em> axis played a crucial role in osteogenic differentiation, with knockdown of <em>Ciart</em> reversing the osteogenic-promoting effects of circCacna1c. In conclusions, the circCacna1c/miR-7669-3p/<em>Ciart</em> pathway is involved in regulating the osteogenic differentiation of BMSCs and may serve as a potential therapeutic target for osteoporosis. Modulating circCacna1c expression or its downstream signaling could offer novel strategies for the treatment and management of osteoporosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110678"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740685","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":"Characterization of the enzymatic activity of the rhythmic human NADP(H) phosphatase, Nocturnin","authors":"Crystal Olivas-Rasmussen,&nbsp;Lauren Palluth,&nbsp;Emil Sjulstok Rasmussen,&nbsp;Carla B. Green","doi":"10.1016/j.abb.2025.110692","DOIUrl":"10.1016/j.abb.2025.110692","url":null,"abstract":"<div><div>NAD(P)(H) is an essential cofactor for metabolic processes and a protector against oxidative stress. Phosphorylation of NAD(H) is completed by NAD kinase while dephosphorylation is performed by Nocturnin (NOCT). Because the phosphatase activity of NOCT is a rather new discovery, its enzymatic mechanism has not been reported. In this study, we use classical steady-state kinetics and pH-rate profiles of site-directed mutants in the NOCT active-site to deduce the essential residues for catalytic function for dephosphorylation of NADP(H). The pH-rate profile is bell shaped which supports that NOCT performs acid-base catalysis. Site-directed mutagenesis showed N149 is important for coordinating a deprotonated nearby residue, which is likely D324, and activates a nearby water to act as the nucleophile. After hydrolysis is performed, protonated H286 donates the proton to the leaving group. Finally, NAD(H) and inorganic phosphate is released. Since NOCT has been implicated in many important metabolic and stress response-related processes, understanding the mechanism is essential for the development of pharmacological modulators of NOCT activity.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110692"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699259","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":"Adrenodoxin alters human cytochrome P450 27A1 structure and reaction efficiency beyond supplying electrons","authors":"Quoc T. Vu ,&nbsp;Katherine C. May ,&nbsp;Leonard B. Collins ,&nbsp;Ying Xi ,&nbsp;Zachary B. Davis ,&nbsp;Jackson L. Bartholomew-Schoch ,&nbsp;Lindsay R. Vaughn ,&nbsp;Katherine R. Provost ,&nbsp;Noah L. Arnold ,&nbsp;Ethan F. Harris ,&nbsp;Emma K. Stone ,&nbsp;Hayden K. Campbell ,&nbsp;Lyndsay M. Snider ,&nbsp;Taufika Islam Williams ,&nbsp;Michael J. Reddish","doi":"10.1016/j.abb.2025.110700","DOIUrl":"10.1016/j.abb.2025.110700","url":null,"abstract":"<div><div>Human cytochrome P450 (P450) 27A1 catalyzes the hydroxylation of cholesterol and vitamin D derivatives. P450 27A1 is localized in the mitochondria and is reduced by its redox partner protein adrenodoxin twice for each catalytic cycle. The reliance on adrenodoxin is conserved across all human mitochondrial P450 enzymes. This study examines the adrenodoxin interaction with P450 27A1 and draws comparisons with studies of other P450 enzymes to determine if differences exist. The P450-adrenodoxin complex structure was examined by chemical crosslinking and analyzed by mass spectrometry. The effect of adrenodoxin concentration on P450 27A1 function was assessed by studying effects on steady state enzyme kinetics parameters and equilibrium substrate binding. The results suggest that adrenodoxin binds to P450 27A1 at a proximal site like other P450 enzymes but differs in the specific residues involved. Furthermore, the presence of adrenodoxin and/or substrate decreases the number of interprotein and intraprotein crosslinks observed, indicating that these components change the conformation of the P450 enzyme. Increased adrenodoxin concentration causes the P450 and vitamin D₃ <em>k</em>_<em>cat</em> value to increase, the <em>k</em>_<em>cat</em><em>/K</em>_<em>m</em> value to decrease, and the substrate <em>K</em>_d to remain constant. These results suggest adrenodoxin alters enzyme efficiency beyond electron transfer without affecting substrate loading. The adrenodoxin effects on P450 27A1 kinetics and equilibrium constants differ from those of other human mitochondrial P450 enzymes. In total, these structural and functional studies suggest that while the general adrenodoxin binding site and function is conserved across P450 enzymes, the details and additional effects of this interaction vary.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110700"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826576","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 C is essential for proper myogenic differentiation","authors":"Yoshitaka Kondo ,&nbsp;Ayami Sato ,&nbsp;Noritsugu Osakabe ,&nbsp;Tatsuki Minowa ,&nbsp;Yung-Li Hung ,&nbsp;Shuichi Machida ,&nbsp;Akihito Ishigami","doi":"10.1016/j.abb.2025.110704","DOIUrl":"10.1016/j.abb.2025.110704","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin C (VC) is naturally present in the blood and skeletal muscles. However, conventional myoblast culture media typically lack VC. Because VC exists in skeletal muscle, VC-supplemented media should better represent physiological conditions than VC-deficient media. Therefore, we used a VC-supplemented culture medium to examine the effects of VC deficiency on myogenic differentiation.</div></div><div><h3>Methods</h3><div>Mouse C2C12 myoblasts were cultured in VC-supplemented or VC-free differentiation medium (DM), with the medium replaced every 24 h to preserve the efficacy of VC.</div></div><div><h3>Results</h3><div>First, we confirmed that VC was reliably taken up by the C2C12 cells. We assessed the expression of muscle regulatory factors during myogenic differentiation. The expression levels of late-stage differentiation markers, including myogenin (<em>MyoG</em>), myomaker (<em>Mymk</em>), myosin heavy chain 1 (<em>Myh1</em>), and <em>Myh4</em> were elevated in VC-free DM during the early stages of myogenic differentiation. In contrast, the expression levels of terminal myogenic markers in mature myofibrils, such as troponin I slow skeletal muscle (<em>Tnni1</em>) and troponin I fast skeletal muscle (<em>Tnni2</em>), increased in cells differentiated in VC-free DM but were lower than those in cells differentiated in VC-supplemented DM. The diameters of the differentiated myotubes were smaller in VC-free DM than in VC-supplemented DM. The levels of 5-hydroxymethylcytosine (5-hmC), a product of the VC-dependent DNA demethylation enzyme ten-eleven translocation (Tet), were markedly lower in VC-free DM.</div></div><div><h3>Conclusion</h3><div>These results suggest that VC modulates myogenic differentiation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110704"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800053","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":"Quercetin enhances muscle FNDC5/irisin, partly through AMPK activation, and induces white adipose tissue browning in high-fat-fed rats","authors":"Victoria Muscia Saez ,&nbsp;Diahann Jeanette Perdicaro ,&nbsp;Cecilia Rodriguez Lanzi ,&nbsp;Eleonora Cremonini ,&nbsp;Patricia Oteiza ,&nbsp;Marcela Alejandra Vazquez Prieto","doi":"10.1016/j.abb.2025.110708","DOIUrl":"10.1016/j.abb.2025.110708","url":null,"abstract":"<div><div>Irisin is a myokine released during physical activity that contributes to the browning of white adipose tissue (WAT), providing various metabolic benefits. We previously demonstrated that supplementation with the flavonoid quercetin (Q) alleviates high-fat diet (HFD) induced visceral WAT hypertrophy, inflammation, and insulin resistance in rats. In this study, we aimed to investigate whether these beneficial effects might be associated with the ability of Q to upregulate muscle fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin and uncoupling protein-1 (UCP-1), along with other brown fat markers in inguinal WAT (iWAT). HFD-fed rats for 6 weeks showed reduced muscle protein levels of FNDC5 and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) compared to the control (Ctrl) group. Q supplementation (20 mg/kg/body weight (BW)/day) reverted these adverse effects of the HFD, significantly increasing muscle p-AMPK as well as plasma irisin levels. Furthermore, Q upregulated key proteins involved in WAT browning (PR domain containing 16 (PRDM16), PGC-1α, PPARɣ and UCP-1) and mitigated HFD-induced iWAT mass gain and hypertrophy. To further investigate the effects of Q on the FNDC5/irisin pathway, L6 myotubes were stimulated with palmitate. Q (1 μM) prevented palmitate-induced decreased levels of p-AMPK and FNDC5, and cell media secreted irisin. Moreover, Q prevented palmitate-mediated decreased Pgc1α and Fndc5 mRNA levels. Transfecting L6 myotubes with Pgc-1α siRNA revealed that Pgc-1α was involved in Q-mediated upregulation of FNDC5. Overall, results show that Q could attenuate HFD-induced iWAT hypertrophy partly through the upregulation of the FNDC5/irisin pathway in muscle and promoting WAT browning. Consumption of Q-rich foods may help mitigate adiposity associated with the consumption of diets rich in saturated fats.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"776 ","pages":"Article 110708"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779789","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}