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Cell Metabolism · 2025 · IF 30.9

Fasting-induced ketogenesis sensitizes bacteria to antibiotic treatment

Shujun Cui,Danyang Chong,Yi-Xin Wang,Huixian Tong,Minggui Wang,Guo-Ping Zhao,Liang-Dong Lyu

Fasting metabolism is a commonly observed motivational response to acute infections and is conceptualized as being beneficial for host survival. Here, we show that fasting potentiates antibiotic treatment for murine sepsis caused by Salmonella Typhimurium, Klebsiella pneumoniae , and Enterobacter cloacae , resulting in increased bacterial clearance and improved host immune responses and survival. This effect is mediated by fasting-induced ketogenesis and could be alternatively implemented by combination therapy with antibiotics and ketone bodies. We show that the ketone body acetoacetate is an effector that sensitizes bacteria to antibiotic treatment by increasing antibiotic lethality and outer and inner membrane permeability. Our results demonstrate that acetoacetate depletes bacterial amino acids, particularly positively charged amino acids and putrescine, leading to cell membrane malfunctions and redox-related lethality. This study reveals an unrecognized role of ketogenesis in antibiotic treatment and a potential ketone body-based treatment strategy for bacterial sepsis.

CAS / MDL: 90-30-2
研究领域: 微生物学 · 医学 · 感染病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ARCHIVES OF MEDICAL RESEARCH · 2020 · IF 2.093

Astragaloside IV as Potential Antioxidant Against Diabetic Ketoacidosis in Juvenile Mice Through Activating JNK/Nrf2 Signaling Pathway

Li-li Deng

Object Astragaloside IV (AS IV) has antioxidative and anti-apoptotic properties, however, its effects on juvenile mice with diabetic ketoacidosis (DKA) have not been determined. This study aims to explore the effect and mechanism of Astragaloside IV (AS-IV) on juvenile mice with DKA. Methods DKA model was established through intraperitoneal injection of streptozotocin (STZ) and alloxan (ALX). DKA mice were divided into Control group, DKA group, DKA+AS-IV group, DKA+AS-IV+SP600125 group, DKA+AS-IV+Anisomycin group, DKA+AS-IV+GV248 group and DKA+AS-IV+GV248-Nrf2 group. To verify the implication of JNK signal pathway, JNK inhibitor SP600125 and activator Anisomycin were injected. The effects of AS-IV on antioxidant capacity and pathologies of pancreatic tissues in DKA juvenile mice were assessed. The expression of JNK/Nrf2 signal pathway was measured by Western blot. Results DKA juvenile mouse models were successfully established, evidenced by elevated blood glucose and blood ketone, suppressed insulin and pH value, and notable injuries in pancreatic tissues. Gavage of AS-IV can enhance antioxidant capacity of pancreatic tissue and ameliorate injuries in pancreatic tissues. AS-IV increased insulin level, in addition to suppressing blood glucose in DKA juvenile mice. In pancreatic tissues of DKA juvenile mice, protein level of p-JNK/JNK in pancreatic tissue and Nrf2 in the nuclei were increased after administration of AS-IV. Inhibition on JNK/Nrf2 signal pathway would impair the favorable effect of AS-IV on DKA juvenile mice, while antioxidant capacity, insulin level and blood glucose were improved in DKA juvenile mice injected an activator of JNK/Nrf2 pathway. Conclusion Collectively, AS-IV can enhance the antioxidant capacity of DKA juvenile mice to decrease blood glucose and to increase serum insulin secretion. The mechanism of action may be realized through the JNK/Nrf2 pathway.

研究领域: 药理学 · 内分泌学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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APPLIED SPECTROSCOPY · 2025 · IF 2.2

EXPRESS: Detection of β-Hydroxybutyric Acid Based on a Fluorescent Probe of Lanthanide Complexes

XingYi Guo,Chun Zhu,Guoqing Chen,Lei Li,Chaoqun Ma,Taiqun Yang,Anqi Hu,WenHui Yang,YaLi Qian

In this paper, a lanthanide complex-based fluorescent sensor Tb(4-MBA) was developed for the selective recognition of diabetic ketoacidosis (DKA) and the diabetes biomarker β-hydroxybutyric (β-Hb). β-Hb significantly enhanced the fluorescence emission of the Tb(4-MBA) complex at 539 nm. Based on the analysis of the surface electrostatic potential distribution and time-resolved spectra, we speculate that in the reaction system of β-Hb with Tb(4-MBA), β-Hb and Tb(4-MBA) may form a complex through hydrogen bonding interactions, which brings β-Hb closer to Tb3+ and thus reduces the non-radiative energy loss of the solvent molecules to Tb3+ and significantly enhances the Tb(4-MBA) fluorescence intensity. The linear range of Tb(4-MBA) for β-Hb was 2–55 μM, and the limit of detection (LOD) was 50.6 nM. This sensor has high sensitivity and selectivity and shows great potential in the field of screening and diagnosis of diabetes mellitus and DKA.

研究领域: 分析化学 · 生物无机化学 · 荧光传感 · 糖尿病研究 · 材料科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Wearable microfluidic electrochemical sensor integrated with iontophoresis for non-invasive sweat ketone monitoring

Yixin Shen,Gangsheng Chen,Yi Chen,Yakun Gao,Chao Hou,Kylin Liao,Biao Ma,Hong Liu

The detection of β-hydroxybutyrate (β-HB) is crucial for the rapid diagnosis of diabetic ketoacidosis and health management. However, daily monitoring of dynamically changing β-HB concentrations is challenging and still limited to laboratory settings or painful and invasive measurements. Herein, we report a wearable electrochemical sensor integrated with iontophoresis for non-invasive monitoring of sweat β-HB. This device can actively stimulate the skin to induce sweat by iontophoresis, and the sweat is controllably collected and transported to the sensing area through the microfluidic channel. The sweat β-HB was measured through an electrochemical oxidation reaction mediated by the generated nicotinamide adenine dinucleotide, which can achieve fast response analysis of sweat β-HB within 40   seconds and a low detection limit of 10   μM. We also used this sensor to monitor the sweat β-HB levels in a volunteer experiencing the ketogenic diet and the sweat and blood β-HB levels exhibited high correlation. We believe this wearable sensor capable of on-demand and noninvasive detection of sweat β-HB shows a wide application prospect in clinical medicine and home healthcare.

研究领域: 生物医学工程 · 传感器 · 可穿戴技术 · 糖尿病管理 · 电化学
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