JOURNAL OF PATHOLOGY
·
2022
·Vol. 258
·期 3
·213-226
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IF 9.883
Zirong Lan,An Chen,Li Li,Yuanzhi Ye,Qingchun Liang,Qianqian Dong,Siyi Wang,Mingwei Fu,Yining Li,Xiaoyu Liu,Zhenyu Zhu,Jing-Song Ou,Xiaozhong Qiu,Lihe Lu,Jianyun Yan
Vascular calcification is an actively regulated process resembling bone formation and contributes to the cardiovascular morbidity and mortality of chronic kidney disease (CKD). However, an effective therapy for vascular calcification is still lacking. The ketone body β-hydroxybutyrate (BHB) has been demonstrated to have health-promoting effects including anti-inflammation and cardiovascular protective effects. However, whether BHB protects against vascular calcification in CKD remains unclear. In this study, Alizarin Red staining and calcium content assay showed that BHB reduced calcification of vascular smooth muscle cells (VSMCs) and arterial rings. Of note, compared with CKD patients without thoracic calcification, serum BHB levels were lower in CKD patients with thoracic calcification. Supplementation with 1,3-butanediol (1,3-B), the precursor of BHB, attenuated aortic calcification in CKD rats and VitD3-overloaded mice. Furthermore, RNA-seq analysis revealed that BHB downregulated HDAC9, which was further confirmed by RT-qPCR and western blot analysis. Both pharmacological inhibition and knockdown of HDAC9 attenuated calcification of human VSMCs, while overexpression of HDAC9 exacerbated calcification of VSMCs and aortic rings, indicating that HDAC9 promotes vascular calcification under CKD conditions. Of note, BHB treatment antagonized HDAC9-induced vascular calcification. In addition, HDAC9 overexpression activated the NF-κB signaling pathway and inhibition of NF-κB attenuated HDAC9-induced VSMC calcification, suggesting that HDAC9 promotes vascular calcification via activation of NF-κB. In conclusion, our study demonstrates that BHB supplementation inhibits vascular calcification in CKD via modulation of the HDAC9-dependent NF-κB signaling pathway. Moreover, we unveil a crucial mechanistic role of HDAC9 in vascular calcification under CKD conditions; thus, nutritional intervention or pharmacological approaches to enhance BHB levels could act as promising therapeutic strategies to target HDAC9 for the treatment of vascular calcification in CKD. © 2022 The Pathological Society of Great Britain and Ireland.
研究领域:
医学
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分子生物学
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DOI
高影响因子
LAB ON A CHIP
·
2025
·
IF 5.4
Tianhao Xue,JiaNing Shen,Wanting Lin,Jiahui Zhou,Xiaofang Zhang,Jen-Tsai Liu,Ching-Jung Chen,Guixian Zhu
Ketone bodies are key products of fat metabolism, primarily consisting of acetoacetate (AcAc), β-hydroxybutyrate (BHB), and acetone (Acetone). Monitoring the concentration of ketone bodies in sweat can reflect the metabolic status of the body, it is also particularly significant in areas such as diabetes management, exercise monitoring, and the evaluation of the ketogenic diet. This paper presents a microfluidic patch for sweat collection and multiplex detection of AcAc, BHB and glucose. The microfluidic patch can achieve time-sequential sensing through Tesla valves, hydrophilic coatings, and unique chamber structural design. The concentrations of the three substances are quantified using colorimetric methods. Additionally, this study has designed a colorimetric app which can achieve automatic framing and detect the grayscale value of the colored area. Experimental results show that the patch can accurately detect changes in the concentrations of the three substances within specific ranges. The linear detection range for AcAc is 0.25 mM to 8 mM, the limit of detection (LOD) is 0.08 mM; for BHB, linear detection range is 0.05 mM to 0.80 mM, LOD is 0.02 mM; and for glucose, linear detection range is 62.50 μM to 1000 μM, LOD is 20.83 μM. In the future, this technology is expected to be applied to portable metabolic monitoring devices, offering a convenient solution for personal health management
研究领域:
生物医学工程
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代谢监测
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健康科技
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF LUMINESCENCE
·
2016
·
IF 2.693
Chaolong Yang,Pan Zhang,Hualin Zhou,Jing Xu,Youbing Li,Mangeng Lu,Lei Lei,Qiang Zhang,Yi Zhang,Shaopeng Chen
A series of environment friendly Eu/PHB fluorescent films through doped the Eu-complex precursor Eu(TTA) 2 (Tpy-OCH 3 )(2H 2 O) into polymer matrices poly-β-hydroxybutyrate (PHB) with doping percentage at 1, 3, 5, and 7 (mass) were designed, fabricated and characterized. TGA and PL results indicated the Eu-complex precursor was immobilized in PHB matrix through the interaction between the Eu-complex. DSC results indicated the crystallinity of Eu/PHB films decreased with the increase of Eu-complex doping percentage. The emission spectra of the Eu-complex and Eu/PHB films recorded at room temperature exhibited the characteristic bands arising from the 5 D 0 / 7 F J . The fact that the quantum efficiencies ( η ) of the doped film increased significantly revealed that the PHB matrix acts as an efficient co-sensitizer for Eu 3+ ions luminescent center and therefore enhances the quantum efficiency of the emitter 5 D 0 level. In particular, all Eu/PHB films can be excited by visible light (410 nm), and also showed good photoluminescent properties. So the new Eu/PHB fluorescent films showed considerable promise for polymer light-emitting diode, active polymer optical fiber and biomedical analysis applications.
研究领域:
材料科学
·
光学
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产品关联
DOI
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2024
·
IF 5.6
Xiaoyong An,Yida Wang,Zhenghao Chen,Jiafei Zhang,Shuangbao Zhang
This study explores a cost-effective and environmentally friendly surface modification of bamboo fibers to improve their interfacial compatibility with poly (β-hydroxybutyric acid). Laccase catalyzed the oxidation of bamboo fibers, increasing their active reaction sites and surface roughness so that the deposition of catechol and tetraethylenepentamine (TEPA) reactions on the bamboo fiber surface was promoted. The FTIR , XPS , and XRD results of bamboo fibers indicate that laccase can effectively oxidize lignin, generating oxygen radicals and promoting the reactive deposition of catechol and TEPA on the surface of the bamboo fibers, without destroying the structure of bamboo fibers. The TGA results of bamboo fibers indicate that when the concentrations of both catechol and TEPA are 15 mM, a laccase concentration of 150 U/L is more effective in enhancing the thermal stability of bamboo fibers. Furthermore, the mechanical properties of BFs/PHB composites showed that the addition of 200 U/L of laccase led to relatively good interfacial compatibility between bamboo fibers and PHB, tensile strength , flexural strength , flexural modulus and impact strength of the composite material respectively increased by 18.4%, 14.1%, 13.4% and 10.4%, while the tensile modulus decreased by 9.4%, compared to the composite material prepared with unmodified bamboo fibers.
研究领域:
材料科学
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生物技术
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环境科学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Jiajia Mu,Qiannan Sun,Nanyan Lin,Chenguang Yue,Jiaqiao Zhu,Hui Zou,Hongyan Zhao,Ruilong Song,Zongping Liu,Yonggang Ma
Ketosis in dairy cows is linked to endometritis, but the molecular mechanisms are unclear. We investigated whether P2X7R is crucial in ketosis-induced endometritis. Ketotic cows had higher levels of NLRP3, caspase-1, GSDMD, GSDME, and P2X7R in the uterine tissue. β-Hydroxybutyric acid (BHBA) exposure in bovine endometrial epithelial cells induced pyroptosis, increased pyroptosis protein and gene expression, and raised pyroptosis rates. P2X7R levels rose with BHBA, and BHBA also increased the level of extracellular ATP. Inhibitors of NLRP3, caspase-1, caspase-3, and P2X7R reduced BHBA-induced pyroptosis. P2X7R inhibition suppressed NLRP3, caspase-1, and caspase-3 activation, preventing pyroptosis. In P2rx7–/– mice with a ketosis model, blood BHBA was lower, and uterine tissue showed less pyroptosis-related protein expression compared to ketotic mice. P2X7R appears to regulate BHBA-induced pyroptosis through NLRP3 and caspase-3 signaling, suggesting it is a potential therapeutic target.
研究领域:
兽医学
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生殖生物学
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细胞生物学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Nature Nanotechnology
·
2025
·
IF 34.9
Xu Jianchang,Zhang Yang,Zhao Sheng,Zhang Juan,Wang Yanfang,Liu Wei,Ji Kangfan,Xu Guangzheng,Wen Ping,Wei Xinwei,Mei Shaoqian,Lu Leihao,Yao Yuejun,Liu Feng,Ma Yufei,You Jiahuan,Gao Jianqing,Buse John B.,Wang Jinqiang,Gu Zhen
The nuclear envelope serves as a highly regulated gateway for macromolecule exchange between the nucleus and cytoplasm in eukaryotes. Here we have developed a cell nucleus-mimicking polymeric membrane-enclosed system for long and self-regulated therapy. A polymeric nano-membrane with nanopores is conformally synthesized in situ on the surface of each insulin crystal, ensuring sustained, adjustable and zero-order drug release kinetics. Glucose- and β-hydroxybutyrate-dually sensitive microdomains are integrated into the nano-membranes. Under a normal state, the microdomains are uncharged and the channel is narrow enough to block insulin outflow. Under hyperglycaemia and ketonaemia, microdomains convert the high glucose and β-hydroxybutyrate concentration signals to the negative electric potential of membranes, widening the nanopores with rapid insulin outflow. In type 1 diabetic mice and minipigs, this system can maintain normoglycaemia for longer than 1 month and 3 weeks, respectively, with validated glucose- and β-hydroxybutyrate-triggered insulin release. Such membrane-enclosed drug crystal/powder formulation provides a broad platform for long-acting controlled release.
研究领域:
生物医学工程
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糖尿病治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
DIABETES RESEARCH AND CLINICAL PRACTICE
·
2025
·
IF 7.4
Mei He,Weiguang Luo,Shuwei Ning,Yuexin Yu,Bin Yang,Zhikun Guo
Objective Beta-hydroxybutyrate (BHB) has been demonstrated to enhance cardiac function in patients with diabetic cardiomyopathy (DCM), the underlying mechanism remains unclear. Methods A DCM rat model was established, BHB was administered via intraperitoneal injection. The therapeutic effects of BHB were assessed based on cardiac function, fasting glucose levels, myocardial fibrosis markers and myocardial macrophage polarization. To elucidate the mechanism of action, co-culture experiments were conducted using cardiac fibroblasts and peritoneal macrophages to evaluate collagen expression in fibroblasts and macrophage polarization under BHB treatment. Results BHB improved cardiac function in DCM rats, reduced fasting glucose levels, alleviated cardiac fibrosis and modulated macrophage polarization. After BHB treatment, the proportion of M1 macrophages decreased while that of M2 macrophages increased in the myocardium of DCM rats. Cardiac fibroblasts isolated from neonatal rats, when co-cultured with peritoneal macrophages under high-glucose conditions, exhibited altered macrophage polarization and collagen expression. High-glucose conditions promoted an increase in M1 macrophages and a decrease in M2 macrophages. BHB treatment reversed this trend by reducing M1 macrophages and promoting M2 macrophage polarization. Conclusions We show that BHB mitigates cardiac fibrosis in DCM rats by promoting M2 macrophage polarization. BHB may be a useful therapeutic approach for DCM treatment.
研究领域:
心脏病学
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内分泌学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
ChemSusChem
·
2018
·Vol. 11
·期 14
·2382-2387
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IF 7.411
Zhongjian Li,Gang Li,Xinlu Chen,Zheng Xia,Jiani Yao,Bin Yang,Lecheng Lei,Yang Hou
Graphical Confining metal inside carbon : Ni nanoparticles are embedded into N-doped carbon nanotubes (Ni@N-C) by rational catalyst design. The Ni@N-C catalyst exhibits high catalytic activity and good biocompatibility, which is further coupled with Cupriavidus necator H16 in a water splitting–biosynthetic system to achieve efficient conversion of CO 2 to poly-β-hydroxybutyrate. CO 2 reduction has drawn increasing attention owing to the concern of global warming. Water splitting–biosynthetic hybrid systems are novel and efficient approaches for CO 2 conversion. Intimate coupling of electrocatalysts and biosynthesis requires the catalysts possess both high catalytic performance and excellent biocompatibility, which is a bottleneck of developing such catalysts. Here, a complex of Ni nanoparticles embedded in N-doped carbon nanotubes (Ni@N-C) is synthesized as a hydrogen evolution reaction electrocatalyst and is coupled with a hydrogen oxidizing autotroph, Cupriavidus necator H16, to convert CO 2 to poly-β-hydroxybutyrate. In Ni@N-C, the Ni nanoparticles are encapsulated in N-C nanotubes, which prevents bacteria from direct contact with Ni and inhibits Ni 2+ leaching. As a result, Ni@N-C exhibits excellent biocompatibility and stability. This work demonstrates that electrocatalysts and biosynthesis can be intimately coupled through rational catalyst design.
研究领域:
生物技术
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环境科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2019
·Vol. 47
·期 6
·582-591
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IF 3.354
Mengru Bai,Qingquan Zeng,Yingchun Chen,Mingyang Chen,Ping Li,Zhiyuan Ma,Dongli Sun,Hui Zhou,Caihong Zheng,Su Zeng,Huidi Jiang
l-Carnitine (l-Car) plays a crucial role in fatty acid β-oxidation. However, the plasma l-Car concentration in women markedly declines during pregnancy, but the underlying mechanism and its consequences on maternal hepatic β-oxidation have not yet been clarified. Our results showed that the plasma l-Car level in mice at gestation day (GD) 18 was significantly lower than that in nonpregnant mice, and the mean fetal-to-maternal plasma l-Car ratio in GD 18 mice was 3.0. Carnitine/organic cation transporter 2 (OCTN2) was highly expressed in mouse and human placenta and upregulated as gestation proceeds in human placenta, whereas expressions of carnitine transporter (CT) 1, CT2, and amino acid transporter B0,+ were extremely low. Further study revealed that renal peroxisome proliferator–activated receptor α (PPARα) and OCTN2 were downregulated and the renal l-Car level was reduced, whereas the urinary excretion of l-Car was lower in late pregnant mice than in nonpregnant mice. Meanwhile, progesterone (pregnancy-related hormone) downregulated the expression of renal OCTN2 via PPARα-mediated pathway, and inhibited the activity of OCTN2, but estradiol, corticosterone, and cortisol did not. Unexpectedly, the maternal hepatic level of l-Car and β-hydroxybutyrate (an indicator of mitochondrial β-oxidation), and mRNA levels of several enzymes involved in fatty acid β-oxidation in GD 18 mice were higher than that in nonpregnant mice. In conclusion, OCTN2 mediated l-Car transfer across the placenta played a major role in maternal plasma l-Car reduction during pregnancy, which did not subsequently result in maternal hepatic fatty acid β-oxidation decrease.
研究领域:
生理学
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药理学
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内分泌学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-13
·
IF 17.694
Pan An,Sun Xiao-Meng,Huang Feng-Qing,Liu Jin-Feng,Cai Yuan-Yuan,Wu Xin,Alolga Raphael N.,Li Ping,Liu Bao-Lin,Liu Qun,Qi Lian-Wen
Disordered hepatic glucagon response contributes to hyperglycemia in diabetes. The regulators involved in glucagon response are less understood. This work aims to investigate the roles of mitochondrial β-oxidation enzyme HADHA and its downstream ketone bodies in hepatic glucagon response. Here we show that glucagon challenge impairs expression of HADHA. Liver-specific HADHA overexpression reversed hepatic gluconeogenesis in mice, while HADHA knockdown augmented glucagon response. Stable isotope tracing shows that HADHA promotes ketone body production via β-oxidation. The ketone body β-hydroxybutyrate (BHB) but not acetoacetate suppresses gluconeogenesis by selectively inhibiting HDAC7 activity via interaction with Glu543 site to facilitate FOXO1 nuclear exclusion. In HFD-fed mice, HADHA overexpression improved metabolic disorders, and these effects are abrogated by knockdown of BHB-producing enzyme. In conclusion, BHB is responsible for the inhibitory effect of HADHA on hepatic glucagon response, suggesting that HADHA activation or BHB elevation by pharmacological intervention hold promise in treating diabetes.
研究领域:
内分泌学
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代谢学
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分子生物学
·
糖尿病研究
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Shendong Zhou,Nana Ma,Meijuan Meng,Guangjun Chang,Xiangzhen Shen
Ketosis in dairy cows is often accompanied by the dysregulation of lipid homeostasis in the liver. Acetyl-coenzyme A acetyltransferase 2 (ACAT2) is specifically expressed in the liver and is important for regulating lipid homeostasis in ketotic cows. Lentinan (LNT) has a wide range of pharmacological activities, and this study investigates the protective effects of LNT on β-hydroxybutyrate (BHBA)-induced lipid metabolism disorder in bovine hepatocytes (BHECs) and elucidates the underlying mechanisms. BHECs were first pretreated with LNT to investigate the effect of LNT on BHBA-induced lipid metabolism disorder in BHECs. ACAT2 was then silenced or overexpressed to investigate whether this mediated the protective action of LNT against BHBA-induced lipid metabolism disorder in BHECs. Finally, BHECs were treated with LNT after silencing ACAT2 to investigate the interaction between LNT and ACAT2. LNT pretreatment effectively enhanced the synthesis and absorption of cholesterol, inhibited the synthesis of triglycerides, increased the expression of ACAT2, and elevated the contents of very low-density lipoprotein and low-density lipoprotein cholesterol, thereby ameliorating BHBA-induced lipid metabolism disorder in BHECs. The overexpression of ACAT2 achieved a comparable effect to LNT pretreatment, whereas the silencing of ACAT2 aggravated the effect of BHBA on inducing disorder in lipid metabolism in BHECs. Moreover, the protective effect of LNT against lipid metabolism disorder in BHBA-induced BHECs was abrogated upon silencing of ACAT2. Thus, LNT, as a natural protective agent, can enhance the regulatory capacity of BHECs in maintaining lipid homeostasis by upregulating ACAT2 expression, thereby ameliorating the BHBA-induced lipid metabolism disorder.
研究领域:
兽医学
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分子生物学
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药理学
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动物生理学
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DOI
PubMed
高影响因子
Science China-Life Sciences
·
2022
·Vol. 66
·期 7
·1569-1588
·
IF 10.372
Ma Ning,Guo Pingting,Chen Jingyu,Qi Zengkai,Liu Chunchen,Shen Jiakun,Sun Yiwei,Chen Xiyue,Chen Guo-Qiang,Ma Xi
Maintainance of sulfomucin is a key end point in the treatment of diarrhea and inflammatory bowel disease (IBD). However, the mechanisms underlying the microbial sense to sulfomucin are poorly understood, and to date, there are no therapies targeting the secretion and maturation of sulfomucin in IBD. Herein, we biosynthesized poly-β-hydroxybutyrate (PHB) and found that PHB could alleviate inflammation caused by diarrhea and colitis by enhancing the differentiation of sulfomucin. Microbiota transplantation and clearance together demonstrate that PHB promoting sulfomucin is mediated by Lactobacillus johnsonii ( L. johnsonii ). Further studies revealed that PHB provides a favorable niche for L. johnsonii biofilm formation to resist disturbance and support its growth. L. johnsonii -biofilm alleviates colitis by regulating fucose residues to promote goblet cell differentiation and subsequent sulfomucin maturation. Importantly, PHB alleviates colitis by enhancing sulfomucin secretion and maturation in a L. johnsonii -dependent manner. PHB represents a class of guardians, acting as a safe probiotic-biofilm delivery system that significantly promotes probiotic proliferation. Altogether, this study adds weight to the possible role of probiotics and functional materials in the treatment of intestinal inflammation. The application of PHB and biofilm self-coating L. johnsonii carries high translational potential and may be of clinical relevance.
研究领域:
胃肠病学
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微生物学
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药学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）