BIOLOGICAL TRACE ELEMENT RESEARCH
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2026
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IF 4.3
Liu Bai Han,Zhang Jin Ge,Peng Dong Qiao,Jin Yong Cheng
Copper is an essential trace element for beef cattle, yet its muscle developmental regulatory mechanism remains unclear. This study investigated the effects of copper sulfate (CuSO₄) on myogenic differentiation of bovine skeletal muscle-derived cells (BSMC) and the underlying molecular mechanisms. BSMC were isolated from the longissimus thoracis muscle of three 30-month-old crossbred steers, with each steer defined as an independent experimental unit corresponding to a separate biological replicate ( n = 3). Based on cell viability, CuSO₄ was used at 0, 0.1, 1, and 10 µM. All cell samples were harvested at differentiation day 6 (D6). The 0.1 µM CuSO₄ treatment during cell growth significantly promoted D6 myotube formation ( P = 0.049), and upregulated mRNA and protein expression of myogenic differentiation 1 (MyoD) ( P = 0.044, P = 0.030), as well as protein expression of hypoxia-inducible factor-1α (HIF-1α) ( P = 0.037) and β-catenin ( P = 0.050). During differentiation, 1 µM CuSO₄ significantly facilitated D6 myotube formation ( P = 0.0004), increased myogenic factor 5(Myf5) mRNA and protein expression ( P = 0.030, P = 0.006), and elevated HIF-1α ( P = 0.025) and β-catenin ( P = 0.004) protein levels, whereas Wnt10b protein expression remained unaltered ( P = 0.930). Single or combined pharmacological inhibition of HIF-1α and β-catenin markedly reversed copper’s pro-myogenic effect on BSMC. In conclusion, copper modulates BSMC myogenic differentiation via the HIF-1α/β-catenin axis by enhancing β-catenin protein stability independent of Wnt10b transcription. HIF-1α acts upstream to drive β-catenin, and a reciprocal regulatory relationship may exist in which β-catenin in turn helps sustain HIF-1α abundance, thereby supporting cascade signaling and downstream myogenic transcription. This study elucidates copper’s molecular mechanism governing muscle development and provides theoretical support for precise copper supplementation to improve beef production performance.
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高影响因子
Biomedical Materials
·
2026
·Vol. 21
·期 3
·035012
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IF 3.9
Xuefei Xiang,Yufang Yang,Heyou Gao,ZhiYun Chen,JingYi Xie,QingChuan Hu,Yu Wang
Composite scaffolds composed of porous polyurethane (PU) block copolymer and nano-hydroxyapatite (n-HA) have demonstrated significant potential in bone defect repair. However, the co-effect of osteogenesis and angiogenesis during the process of large bone defect repair is still not yet fully understood. Recent research has found that erythropoietin (EPO) is essential for both osteogenesis and angiogenesis, offering a new research direction for bone regeneration strategies. In this study, a polydopamine (pDA)-modified, EPO-functionalized HA/PU scaffold was fabricated, and its physicochemical properties, release kinetics, and effects on bone repair were systematically investigated. In vitro, a co-culture system of human umbilical vein endothelial cells and rat bone marrow mesenchymal stem cells was used to evaluate the scaffold’s effects on cell proliferation, osteogenic, angiogenic, and HIF-1α/ vascular endothelial growth factor (VEGF) pathway. In vivo, the modified composite scaffold was implanted onto the cranial bone defects of Sprague-Dawley rats to assess its efficacy in promoting bone repair and HIF-1α/VEGF pathway. In vitro, the EPO/pDA/HA/PU group showed more three-dimensional cell morphology with prominent pseudopodia, facilitating cell adhesion, and significantly increased mRNA expression of ALP, Runx2, CD31, CD34, HIF-1α and VEGF. In vivo, the EPO/pDA/HA/PU group exhibited the most significant bone regeneration, with micro- computed tomography analysis confirming a significantly higher the ratio of bone tissue volume to total tissue volume (BV/TV) compared to the blank and HA/PU control groups. These results indicated that the modified composite scaffold enabled sustained release of EPO, which upregulated the expression of HIF-1α and VEGF, thereby enhancing osteogenic and angiogenic capabilities both in vitro and in vivo. Our research demonstrated that loading of EPO onto the HA/PU composite scaffold could effectively promote osteogenesis and angiogenesis. HIF-1α/VEGF signaling plays a crucial role in this process. This discovery provides novel insights and methods for using HIF-1α/VEGF as a regulatory target to advance the clinical translation of large bone defects repair.
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高影响因子
Frontiers in Nutrition
·
2026
·
IF 5.5
Binhong Hu,Ling Yao,Xin Deng,Wei Zhao,Kuo Chen,Jiacheng Zhang,Zhiqiang Li,Jin-ping Li,Wei Jiang,Huabao Liu
AimsThis study aims to explore the potential therapeutic effect of Dendrobium officinale polysaccharide (DOP) on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD), and to elucidate the underlying mechanism involving the SIRT6/PGC-1α signaling axis and the regulation of the gut microbiota.MethodsWe extracted and characterized DOP. We established a rat model of NAFLD induced by HFD and evaluated the efficacy of DOP by integrating multi-omics techniques (transcriptomics, metabolomics) and 16S rRNA sequencing. To verify the specific role of SIRT6, we introduced the SIRT6 inhibitor OSS_128167 in the primary hepatocyte model induced by oleic acid/palmitic acid (OA/PA).ResultsDOP significantly alleviated liver steatosis, oxidative stress, and lipid metabolism disorders induced by HFD. Multi-omics analysis indicated that DOP regulated liver glycerophospholipid metabolism and restored intestinal microbiota homeostasis, significantly increasing the abundance of beneficial bacteria such as Lactobacillus. Mechanistically, DOP activated the liver SIRT6/PGC-1α signaling axis, thereby enhancing antioxidant defense and inhibiting lipogenesis. Crucially, in vitro experiments confirmed that the SIRT6 inhibitor OSS_128167 eliminated the protective effect of DOP on lipid accumulation, confirming that the effect of DOP depends on SIRT6.ConclusionDOP improves NAFLD through dual mechanisms of regulating the gut-liver axis homeostasis and directly activating the liver SIRT6/PGC-1α signaling pathway. The results of this study provide a theoretical basis for developing DOP as a drug for the treatment of NAFLD.
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BIORESOURCE TECHNOLOGY
·
2026
·
IF 8.2
Fan He,Qiaoqiao Ma,Huahua Zhang,Junheng Gou,Qingbo Deng,Jinsong Gong,Jinsong Shi,Zhenghong Xu,Hui Li
1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2 VD 3 ), the biologically active form of Vitamin D 3 (VD 3 ), plays a crucial role in a wide range of physiological processes. However, the efficient biosynthesis of 1α,25(OH) 2 VD 3 is hindered by the low activity of natural enzymes, poor solubility of substrate VD 3 , and its intracellular metabolic loss. Herein, we developed an integrated bioprocess by synergizing engineered dihydroxylase (CYP109A2-H) with a deep eutectic solvent (DES) based resting cell system to overcome these limitations. A semi-rational design strategy was employed to enhance the performance of the enzyme, which yielded several beneficial mutants including E81G that increased the catalytic titer by 43.6%. Concurrently, a DES resting cell system was constructed, wherein DES dramatically increased VD 3 solubility and resting cells eliminated metabolic loss. This synergistic strategy achieved a record-high 1α,25(OH) 2 VD 3 space–time yield of 33.15 mg·L −1 ·d −1 , establishing the most efficient single-batch bioconversion reported to date. This work provides a sustainable and efficient platform for 1α,25(OH) 2 VD 3 production and a general strategy for the biohydroxylation of hydrophobic compounds.
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Journal of Functional Foods
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2026
·
IF 3.9
Zexuan Wu,Yonghong Long,Fugang Huang,Ze Yang,Yanzuo Wu,Yihong Gan,Xiufang Chen,Guanqun Xie
Capsaicin (CAP), the pungent compound in chili peppers, is well-known for its anti-inflammatory properties, yet its role in autoimmune immunometabolism remains unexplored. In a murine model of Collagen-Induced Arthritis,CAP markedly attenuated joint swelling, cartilage damage, and bone erosion. Mechanistically, CAP targeted HIF-1α, leading to a coordinated suppression of both BNIP3-mediated mitophagy and the characteristic glycolytic shift in M1 macrophages. This dual metabolic suppression was recapitulated in human THP-1-derived M1-like macrophages, where it inhibited M1 polarization and reduced pro-inflammatory cytokine secretion. Collectively, these data identify CAP as a food-derived immunometabolic modulator that alleviates rheumatoid arthritis (RA) by concurrently disrupting mitophagy and glycolysis in M1 macrophages via HIF-1α.
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JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Yuhao Wu,Junke Wang,Tianxin Zhao,Jiadong Chen,Lian Kang,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP) is an extensively used plasticizer and has been shown to cause reproductive dysfunction in humans and model animals. However, the exact mechanisms of testicular injury induced by DEHP exposure have not been fully clarified. Using gas chromatography-mass spectrometry, we found that mono-2-ethylhexyl ester (MEHP, a major biometabolite of DEHP) and DEHP concentrations were elevated in mouse serum after DEHP exposure. Using RNA-seq, we found that ferroptosis and HIF-1 signaling pathways might be involved in testicular injury due to prepubertal DEHP exposure. Subsequent Western blotting, ferrous iron and MDA measurements, and immunofluorescence of testicular sections verified the RNA-seq findings. Consistently, based on the RNA-seq findings, we found that ferroptosis and HIF-1 signaling pathways might play crucial roles in Leydig and Sertoli cell injury due to MEHP exposure in vitro. Further experiments also confirmed ferroptosis in Leydig and Sertoli cells. Using Western blotting, cellular immunofluorescence and ChIP-qPCR, we found that MEHP exposure caused HIF-1α accumulation and stabilization, resulted in HIF-1α translocation into the nucleus, and induced HIF-1α/ Hmox1 binding in Leydig and Sertoli cells. To clarify whether HIF-1α plays a pivotal role in MEHP-induced ferroptosis, we knocked out Hif-1α using the CRISPR/Cas9 technique. We found that Hif-1α knockout rescued MEHP-induced ferroptosis. In summary, our findings certified that prepubertal DEHP exposure led to ferroptosis in mouse testes via the HIF-1α/HO-1 signaling pathway.
研究领域:
毒理学
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生殖生物学
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分子生物学
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Frontiers in Physiology
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2021
·
IF 4.566
Lin Jinyan,Fan Lele,Han Yuming,Guo Juanjuan,Hao Zhiqiang,Cao Lingna,Kang Jiamin,Wang Xiaoqin,He Jianping,Li Jingang
The Gansu zokor (Eospalax cansus) is a subterranean rodent species that is unique to China. These creatures inhabit underground burrows with a hypoxia environment. Metabolic energy patterns in subterranean rodents have become a recent focus of research; however, little is known about brain energy metabolism under conditions of hypoxia in this species. The mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) coordinates eukaryotic cell growth and metabolism, and its downstream targets regulate hypoxia inducible factor-1α (HIF-1α) under conditions of hypoxia to induce glycolysis. In this study, we compared the metabolic characteristics of hypoxia-tolerant subterranean Gansu zokors under hypoxic conditions with those of hypoxia-intolerant Sprague-Dawley rats with a similar-sized surface area. We exposed Gansu zokors and rats to hypoxia I (44 h at 10.5% O2) or hypoxia II (6 h at 6.5% O2) and then measured the transcriptional levels of mTORC1 downstream targets, the transcriptional and translational levels of glycolysis-related genes, glucose and fructose levels in plasma and brain, and the activity of key glycolysis-associated enzymes. Under hypoxia, we found that hif-1α transcription was upregulated via the mTORC1/eIF4E pathway to drive glycolysis. Furthermore, Gansu zokor brain exhibited enhanced fructose-driven glycolysis under hypoxia through increased expression of the GLUT5 fructose transporter and ketohexokinase (KHK), in addition to increased KHK enzymatic activity, and utilization of fructose; these changes did not occur in rat. However, glucose-driven glycolysis was enhanced in both Gansu zokor and rat under hypoxia II of 6.5% O2 for 6 h. Overall, our results indicate that on the basis of glucose as the main metabolic substrate, fructose is used to accelerate the supply of energy in Gansu zokor, which mirrors the metabolic responses to hypoxia in this species.
研究领域:
生理学
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分子生物学
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代谢学
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神经科学
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高影响因子
Scientific Reports
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2026
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IF 4.9
Niu Jiale,Liu Guangxia,He Guangyao,Zhang Xiaomeng,Bai Huihui,Lu Yamin
To investigate the role of IL-17 in macrophage M1 polarization within a type 2 diabetic (T2DM) milieu and to evaluate the therapeutic potential of its neutralizing antibody. PMA-differentiated THP-1 macrophages were polarized to M1 state. Under high glucose, cells were treated with IL-17 and an IL-17 neutralizing antibody. Inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured; mRNA levels of TNF-α, HIF-1α, and NLRP3 were assessed by qPCR; and protein expression related to the NF-κB, mTOR/HIF-1α axis and pyroptosis (NLRP3, Caspase-1, GSDMD) was analyzed by Western Blot. High glucose and IL-17 synergistically promoted M1 polarization, enhancing proinflammatory cytokine secretion. This was associated with activation of the NF-κB, mTOR/HIF-1α signaling axis and induction of pyroptosis, evidenced by NLRP3 inflammasome assembly, Caspase-1 activation, and GSDMD cleavage. The IL-17 neutralizing antibody effectively suppressed these pathological processes. IL-17 acts as a key immunological amplifier in diabetes, driving M1 polarization, oxidative stress, and pyroptosis via the NF-κB, mTOR/HIF-1α axis and NLRP3 inflammasome. Treatment with an αIL-17 effectively reversed the aberrant activation of the aforementioned cellular phenotypes and signaling pathways, partially restoring macrophage functional balance. This finding provides preliminary experimental support for further exploration of IL-17-targeted immunomodulatory strategies to ameliorate diabetes-associated metabolic inflammation.
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BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Reziwanguli Wusiman,Shayila Haimiti,Hanikezi Abuduaini,Miaoyan Yang,Yitian Wang,Meijun Gu,Ali Sailike,Lei Gao
Renal fibrosis is a prominent feature of diabetic nephropathy (DN), and the connection between renal fibrosis and abnormal glycolysis is not fully understood. SUMO-activating enzyme subunit 1 (SAE1) plays a crucial role in the SUMO modification process and is related to abnormal glycolysis. Despite this, the specific role of SAE1 in DN and its mechanism are not well defined. To investigate this, a streptozotocin-induced diabetic CD1 mice model was used, with SAE1 suppression achieved through systemic administration of SAE1 siRNA. In parallel, human renal proximal tubular tubule HK2 cells transfected with siSAE1 were exposed to high glucose for in vitro studies. The study revealed that SAE1 levels were elevated in diabetic kidney, and the deletion of SAE1 mitigated renal fibrosis in DN mice. Such suppression in SAE1 was associated with the lower expression of hypoxia inducible factor-1α (HIF-1α) and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), these alterations subsequently improved abnormal glycolysis and mesenchymal transformations in vivo and in vitro . Further experiments discovered that SAE1 stabilized transcription factor HIF-1α expression through SUMOylation, promoting PFKFB3 transcription, which enhanced glycolysis characterized by increased PFK1 activity and lactate production. Additionally, pharmacological inhibition of PFKFB3 reduced renal fibrosis in DN mice, while overexpression of PFKFB3 partly restored the glycolysis and mesenchymal transformations inhibited by SAE1 knockdown in vitro . These data demonstrate that SAE1 promotes abnormal glycolysis by HIF-1α/PFKFB3 which is responsible for the fibrotic phenotype of diabetic kidney. Inhibition of SAE1 could be an alternative strategy in combating diabetes associated-kidney fibrosis via improving aberrant glycolysis.
研究领域:
肾病学
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分子生物学
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糖尿病学
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高影响因子
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
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2025
·
IF 2.4
Jingjing Lu,Dongxuan Wang,Hongjin Huo,Hao Jiang,Wei Wei,Jie Sun,Fei Jiang
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high metastatic potential and limited therapeutic options. This study investigates the effects of calcitriol, an active metabolite of vitamin D, on TNBC progression by targeting the vitamin D receptor (VDR)-mediated hypoxia-inducible factor-1α (HIF-1α) axis. We established in vivo TNBC xenograft models using 4T1 cells and in vitro models with MDA-MB-231 and 4T1 cells overexpressing HIF-1α. Results showed that calcitriol inhibited lung metastasis and downregulated glycolytic activity in TNBC xenografts without affecting primary tumor growth. In vitro, calcitriol reduced cell viability, migration, and invasion by suppressing HIF-1α expression. It also decreased glucose uptake, lactate production, and ATP levels while downregulating key glycolytic regulators. VDR knockdown abolished these effects, confirming VDR as the critical mediator. Our findings suggest that calcitriol exerts anti-metastatic effects in TNBC by modulating the VDR-HIF-1α axis, inhibiting glycolysis, and suppressing the epithelial-mesenchymal transition. This study highlights the potential therapeutic role of calcitriol in TNBC treatment by targeting both metabolic reprogramming and invasive capacity. Future research should further explore the mechanisms underlying calcitriol-mediated HIF-1α suppression and its clinical application in TNBC.
研究领域:
肿瘤学
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分子生物学
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内分泌学
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癌症代谢
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转化医学
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Bioactive Materials
·
2024
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IF 18
Lili Sun,Haoyi Niu,Yuqiong Wu,Shiyan Dong,Xuefeng Li,Betty Y.S. Kim,Changsheng Liu,Yifan Ma,Wen Jiang,Yuan Yuan
Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.
研究领域:
组织工程
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骨再生
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生物材料
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骨科
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高影响因子
TOXICOLOGY LETTERS
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2018
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IF 3.166
Yisen Cheng,Gaojian Chen,Li Wang,Jiamin Kong,Ji Pan,Yue Xi,Feihai Shen,Zhiying Huang
Triptolide is a major active ingredient of tripterygium glycosides, used for the therapy of immune and inflammatory diseases. However, its clinical applications are limited by severe male fertility toxicity associated with decreased sperm count, mobility and testicular injures. In this study, we determined that triptoide-induced mitochondrial dysfunction triggered reduction of lactate and dysregulation of fatty acid metabolism in mouse Sertoli cells. First, triptolide induced mitochondrial damage through the suppressing of proliferator-activated receptor coactivator-1 alpha (PGC-1α) activity and protein. Second, mitochondrial damage decreased lactate production and dysregulated fatty acid metabolism. Finally, mitochondrial dysfunction was initiated by the inhibition of sirtuin 1 (SIRT1) with the regulation of AMP-activated protein kinase (AMPK) in Sertoli cells after triptolide treatment. Meanwhile, triptolide induced mitochondrial fatty acid oxidation dysregulation by increasing AMPK phosphorylation. Taken together, we provide evidence that the mechanism of triptolide-induced testicular toxicity under mitochondrial injury may involve a metabolic change.
研究领域:
药理学
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毒理学
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生殖生物学
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细胞代谢
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高影响因子
危险品化学品经营许可证（带存储）