SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Bin Jiang,Jiayun Guan,Yilin Lv,Chaojie Yang,Minfeng Yang,Xinyu Shen,Bin Xu,Qi Wang,Yuling Qin,Li Wu
The cholinergic hypothesis constitutes a pivotal theoretical framework for elucidating the pathological mechanisms underpinning Alzheimer's disease (AD). Quantitative assessment of cholinesterases (ChEs) and NAD(P)H levels in neuronal cells, particularly within the septo-hippocampal pathway, is imperative for the comprehensive study of the cholinergic system. In this study, we designed and synthesized a dual-channel, dual-enzyme-responsive fluorescent indicator that was chemically optimized for detecting levels of ChEs and NAD(P)H in neuronal cells. Biological experiments demonstrated that this indicator can sensitively and reliably visualize the dynamics of intracellular ChEs and NAD(P)H following stimulation. The corresponding ChEs activities and NAD(P)H concentrations demonstrated a linear correlation with fluorescence intensity, reaching equilibrium within a few minutes. This innovative and precise technique for visualizing ChEs and NAD(P)H dynamics with high spatial resolution during the progression of AD is expected to serve as a robust tool for investigating alterations in the cholinergic nervous system, including changes in acetylcholine neurotransmission and neuronal energy metabolism.
研究领域:
神经科学
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生物化学
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分子生物学
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医学研究
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荧光成像
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产品关联
DOI
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Hongfei Nie,Yarong Zhang,Haiyang Yu,Hong Xiao,Tao Li,Qian Yang
Nicotinamide riboside (NR), as a dietary supplement, can be converted to nicotinamide adenine dinucleotide (NAD+) in cells to support mitochondrial energy metabolism. However, the efficacy of oral administrated NR is limited due to its quick degradation in circulation and low bioavailability in targeted organs. In this study, we fabricated nanocrystal self-assembled microspheres by Nano Spray Dryer for oral delivery of NR. The structure of NR and resveratrol (RES) nanocrystal self-assembled microspheres (NR/RESms) is confirmed by the morphology, chemical structure, and crystallization. The NR/RESms displayed restricted NR release at the gastric acid-mimic condition (<15% in the first 8 hours), while achieved accelerated NR release in an enteric-mimic environment (>46% within 8 hours). Oral administration of NR/RESms for 8 hours significantly elevated NAD+ levels in serum (169.88 nM versus 30.93 nM in the NR group, p < .01; and 66.89 nM in the NR + RES group, p < .05), and enhanced NAD+ abundance in multiple organs in mice, exhibiting an improved oral NAD+ bioavailability. In addition, without any serious adverse effects on major organs, oral delivery of NR/RESms attenuated myocardial infarction (15.82% versus 19.38% in the I/R + NR group and 20.76% in the I/R + NR + RES group) in a cardiac ischemia/reperfusion (I/R) injury mouse model. Therefore, our data supported that the NR/RESms is a promising candidate as NAD+ booster for oral administration.
研究领域:
药理学
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纳米技术
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心脏病学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Huiying Huang,Jian Shi,Zhongyi Li,Yifeng Rang,Weiye Li,Xueman Xiao,Congying Chen,Chunhong Liu
Nonylphenol (NP) exposure can trigger neurotoxicity and cause learning and memory impairment. Nicotinamide mononucleotide (NMN) has a therapeutic effect on neurodegenerative diseases , but the role of NMN on NP-induced learning and memory impairment is not known. Here, we examined the mitigative effect of NMN on the impaired learning and memory ability of rats exposed to NP. The NP impaired learning and memory in rats, while the low-dose intervention with NMN significantly prolonged the step-through latency of the PAT and improved the NAMPT and NMNAT1 content in brain tissue. At the same time, the NMN intervention also increased the content of 5-HTR 1A , 5-HTR 4 , and 5-HTR 6 related to learning and memory in the hippocampus. In line with this, we found that the NMN intervention activated the SIRT1/MAO-A pathway in brain tissue. NMN intervention, especially at 125 mg/kg doses, may improve rats’ NP-induced learning and memory impairment via the central 5-HT system and the NAD + /SIRT1/MAO-A pathway in the brain.
研究领域:
神经科学
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药理学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Peiling Wu,Wenjie Wang,Chuan Huang,Le Sun,Xiaoli Wu,Lijia Xu,Peigen Xiao
Background TRY-NAD metabolic network includes TRY (tryptophan), 5-HT (5-hydroxytryptamine), KYN (kynurenine), and NAD (nicotinamide adenine dinucleotide) pathway, which plays a significant role in neurological diseases and ageing. It is important to monitor these metabolites for studying the pathological anatomy of disease and treatment of responses evaluation. Although previous studies have reported quantitative methods for several metabolites in the network, the bottlenecks of simultaneously quantifying the whole metabolic network are their similar structures, diverse physico-chemical properties, and instability. Standardized protocols for the whole metabolic network are still missing, which hinders the in-depth study of TRY-NAD metabolic network in laboratory research and clinical screening. Results We developed a LC-MS/MS method for quantifying 28 metabolites in the TRY-NAD network simultaneously. Optimization was done for the mass spectral parameters, chromatographic conditions and sample pretreatment process. The developed method was fully validated in terms of standard curves, sensitivity, carryover, recovery, matrix effect, accuracy, precision, and stability. The pretreatment of 30 samples only takes 90 minutes, and the LC-MS/MS running time of one sample is only 13 minutes. With this method, we bring to light the chaos of global TRY-NAD metabolic network in sleep deprivation mice for the first time, including serum, clotted blood cells, hippocampus, cerebral cortex, and liver. NAD pathway levels in brain and blood decreased, whereas the opposite happened in the liver. The 5-HT pathway decreased and the concentration of KYN increased significantly in the brain. The concentration of many metabolites in KYN pathway (NAD + de novo synthesis pathway) increased in the liver. Significance This method is the first time to determine the metabolites of KYN, 5-HT and NAD pathway at the same time, and it is found that TRY-NAD metabolic network will be disordered after sleep deprivation. This work clarifies the importance of the pH of the extraction solution, the time and temperature control in pretreatment in standardized protocols building, and overcoming the problems of inconsistent sample pretreatment, separation, matrix effect interference and potential metabolite degradation. This method exhibits great prospects in providing more information on metabolic disturbances caused by sleep deprivation as well as neurological diseases and ageing.
研究领域:
分析化学
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神经科学
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药理学
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生物化学
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临床研究
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DOI
PubMed
高影响因子
Nature Communications
·
2026
·
IF 18.1
Chen Xiaoxin,Xu Qi,Liu Yi,Zhu Zhenshuo,Wang Ziqiu,Zhang Yun,Li Ziru,Mao Yunan,Ai Chenmiao,Chen Qi,Tian Le,Yao Zhiying,Gwon Youngdae,Shi Zhubing,Yang Peiguo
Although diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are implicated in host-virus interactions, the specific antiviral mechanisms of certain family members remain largely undefined. Here, we reveal that mono-ADP-ribosyltransferase PARP10 restricts viral replication by forming biomolecular condensates via multivalent interactions among its structured domains. PARP10 condensates enhance enzymatic activity, resulting in increased NAD⁺ consumption that ultimately inhibits viral replication. The antiviral effects of PARP10 are shown to require both its catalytic activity and NAD⁺ regulation, as catalytic mutants and PARP10 inhibitors abrogate these effects, while reduction of NAD⁺ potently restricts viral replication. Furthermore, we identify auto-ADP-ribosylation as an intrinsic negative feedback mechanism modulating PARP10 condensation. These findings establish PARP10 condensation as a compartmentalization strategy that amplifies local NAD⁺ consumption to safeguard host antiviral immunity.
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DOI
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2026
·
IF 4.7
Du Jiangxia,Shen Minhui,Mu Yuan,Peng Shuoran,Xu Zhifei,Yang Xiaochun,Yang Bo,Luo Peihua,Yan Hao,He Qiaojun
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a prevalent chronic liver disorder with complex pathogenesis and limited therapeutic options. Here, we identify the solute carrier SLC13A3 as a critical regulator of MASLD progression. In a mouse model fed a high-fat, high-cholesterol, and high-fructose (HFHCHF) diet, hepatic SLC13A3 expression was significantly upregulated and positively correlated with disease severity. Liver-specific overexpression of Slc13a3 exacerbated hepatic steatosis, lipid accumulation, and metabolic dysfunction, whereas Slc13a3 knockdown attenuated these pathological phenotypes. Targeted metabolomic analysis revealed that SLC13A3 modulates hepatic NAD + levels, thereby influencing the expression of key lipid metabolism genes, including SREBF1 , CD36 , PPARγ , and SCD1 . These findings highlight a previously unrecognized role of SLC13A3 in MASLD pathogenesis and suggest its potential as a therapeutic target.
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产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2020
·Vol. 104
·期 16
·7079-7091
·
IF 3.53
Wang Shengli,Han Jing,Xia Jiale,Hu Yanru,Shi Liang,Ren Ang,Zhu Jing,Zhao Mingwen
Abstract Identifying new and economical means to utilize diverse lignocellulosic biomass is an urgent task. Ganoderma lucidum is a well-known edible and medicinal basidiomycete with an excellent ability to degrade a wide range of cellulosic biomass, and its nutrient use efficiency is closely related to the activity of extracellular cellulase. Intracellular nicotinamide adenine dinucleotide (NAD + ) biosynthesis is controlled in response to nutritional status, and NAD + is an essential metabolite involved in diverse cellular processes. Nicotinamide mononucleotide adenylyltransferase (NMNAT) is a common enzyme in three NAD + synthesis pathways. In this study, a homologous gene of nmnat was cloned from G. lucidum and two G. lucidum overexpression strains, OE::nmnat4 and OE::nmnat19, were constructed using an Agrobacterium tumefaciens -mediated transformation method. The G. lucidum nmnat overexpression strains showed obviously increased colony growth on different carbon sources, and intracellular Ca 2+ concentrations in the G. lucidum OE::nmnat4 and OE::nmnat19 strains were increased by 2.04- and 2.30-fold, respectively, compared with those in the wild-type (WT) strains. In the G. lucidum OE::nmnat4 and OE::nmnat19 strains, endo- β -glucanase (CMCase) activity increased by approximately 2.8- and 3-fold, while β -glucosidase ( p NPGase) activity increased by approximately 1.9- and 2.1-fold, respectively, compared with the activity in the WT strains. Furthermore, overexpression of NAD + synthesis pathways was found to elicit cellulase production by increasing the intracellular Ca 2+ concentration. In summary, this study is the first to demonstrate that increased intracellular NAD + contents through overexpression of the nmnat gene of NAD + synthesis pathways may increase cellulase production by increasing intracellular Ca 2+ concentrations in G. lucidum . Key points
The concentration of NAD
+
influences cellulase production in G. lucidum.
The concentration of NAD
+
influences the intracellular Ca
2+
concentration in G. lucidum.
The concentration of NAD
+
influences cellulase production by eliciting a change in intracellular Ca
2+
in G. lucidum.
研究领域:
微生物学
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生物技术
·
酶学
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DOI
PubMed
高影响因子
Biotechnology Journal
·
2025
·Vol. 20
·期 6
·e70045
·
IF 3.1
Jun-Ping Zhou,Yi-Nan Xue,Feng Wang,Hui Gao,Zhi-Cheng Zhang,Ai-Ping Pang,Zhi-Qiang Liu,Yu-Guo Zheng
Leucine dehydrogenase catalyzes the asymmetric reductive amination of ketoacids to produce valuable chiral unnatural amino acids, but its application is often constrained by substrate inhibition. Here we employed a rational engineering strategy to alleviate substrate inhibition by enhancing the dissociation efficiency of NAD + . Notably, the variant H184A exhibited a 1.53-fold increase in enzyme activity and a 58% improvement in the half-maximal inhibitory concentration for 2-oxobutyric acid, alleviating substrate inhibition.
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DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
·
2022
·
IF 11.889
Lei Yu,Wei-xin Cheng,Quan Wang
Biohydrogen productions from xylose and glucose under dark condition were enhanced by the presence of natural Fe 3 O 4 . The electron equivalent of H 2 fractions accounted for 4.55 % and 5.69 % of the total given xylose and glucose in the experiments without Fe 3 O 4 , and that were correspondingly increased to 5.14 % and 6.50 % in the experiments with 100 mg/L of Fe 3 O 4 , respectively. Moreover, Fe 3 O 4 increased the total intracellular NAD(H) concentrations by 8.84 % and 8.37 %, and boosted the ratios of NADH/NAD + by 8.33 % and 17.72 % in xylose and glucose fermentation, respectively, comparing to the corresponding control experiments. The formation of electron couples of Fe(III)/Fe(II) during the iron oxide respiration and more generation of active extracellular polymeric substances components were determined as the important reasons for the improved biohydrogen production performance. Thus, a promotion mechanism of the internal “driving forces” from extracellular iron oxide respiration on the biohydrogen production was proposed.
研究领域:
生物技术
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环境工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yingchun Zhao,Ying Qu,Changshun Huang,Chengzhilin Li,Wenyu Zhang,Xinyu Wang,Wenlong Duan,Qingbin He,Yachao Zhang,Jianwei Jiao,Runxiao Zheng
Systemic inflammation, excessive reactive oxygen species (ROS) and mitochondrial impairment are the main cause of multi-organ dysfunction syndrome in sepsis. Nevertheless, the pharmaceuticals currently in development focus solely on a single mechanism of disease, which is evidently inadequate. Herein, a precision nanodrug delivery system (MSe-NAD + /Nes) has been designed, incorporating mesoporous selenium nanozymes (MSe NPs) and leveraging a neutrophil-targeting strategy, to accomplish accurate delivery and mitigate inflammation. Upon reaching the inflammatory region, MSe NPs destroys selenium bonds and releases NAD + under the action of ROS, which in turn supplements the NAD + pool and promotes the recovery of mitochondrial function. Moreover, MSe NPs are capable of efficiently eliminating ROS by mimicking the activity of glutathione peroxidase (GPx), thus preventing the activation of the NLRP3 inflammasome. In vivo administration has indicated that MSe-NAD + /Nes efficiently alleviates organ oxidative stress, restores ATP levels, attenuates systemic hyperinflammation, and facilitates rapid organ repair. This study presents a potential modality of inflammation remission via ROS scavenging and mitochondrial repairment for the reliable and safe therapy of sepsis.
研究领域:
纳米医学
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免疫学
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药理学
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炎症研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Cardiovascular Diabetology
·
2025
·Vol. 25
·期 1
·5
·
IF 10.6
Jia Yumeng,Niu Wenhui,Liu Lu,Zhang Qun,Li Dingwei,Dai Tangyu,Du Jie,Wang Lei
Background Disrupted cardiomyocyte energy metabolism is a hallmark of heart failure with preserved ejection fraction (HFpEF). Succinate, a key intermediate of the tricarboxylic acid cycle, is markedly decreased in HFpEF myocardium. In addition to its metabolic role, succinate functions as a signaling molecule that activates GPR91 to regulate metabolic and immune pathways. However, the precise contributions and mechanisms of cardiomyocyte succinate–GPR91 signaling in HFpEF pathogenesis remain incompletely understood. Methods HFpEF models were established in wild-type (WT), global GPR91 knockout (Gpr91 -/- ), and cardiomyocyte-specific GPR91 knockout (Gpr91 ΔCM ) mice, with or without succinate supplementation. Cardiac structure, function, and metabolic phenotypes were assessed using echocardiography, histology, and molecular assays. Transcriptome sequencing of myocardial tissues was performed to identify pathways regulated by succinate–GPR91 signaling. Mechanistic studies in human AC16 cardiomyocytes were conducted to validate pathway regulation and clarify downstream molecular mechanisms. Additionally, rescue experiments were performed to confirm the functional relevance of succinate–GPR91 signaling in cardiomyocyte metabolism and HFpEF progression. Results Cardiac succinate levels and GPR91 expression were markedly decreased in HFpEF mice. Succinate supplementation restored systemic metabolism, improved diastolic function, and attenuated myocardial hypertrophy and fibrosis in WT HFpEF mice, whereas these protective effects were abolished in both Gpr91 -/- and Gpr91 ΔCM mice. Transcriptomic analysis demonstrated that succinate activated AMPK signaling and enriched pathways related to glucose–lipid metabolism and NAD + biosynthesis in Gpr91 fl/fl but not in Gpr91 ΔCM hearts. Mechanistically, succinate enhanced AMPK phosphorylation and NAD + production via Gq-mediated signaling, thereby promoting cardiomyocyte metabolic reprogramming. Conclusion These findings identify the succinate–GPR91 axis as a critical regulator of cardiometabolic homeostasis and a potential therapeutic target in HFpEF. Graphical
研究领域:
心脏病学
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分子生物学
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代谢学
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信号转导
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内分泌学
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DOI
PubMed
高影响因子
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
·
2025
·
IF 2.9
Jianwei Li,Samuel Robertshaw,Shouying Huang,Shelley D. Minteer,Xiaodong Wang
Nicotinamide adenine dinucleotide (NAD+) cofactor regeneration is essential for enabling dehydrogenase-promoted biosynthesis for value-added chemicals. Heterogeneous catalytic cofactor regeneration, using supported metal catalysts, is an emerging approach and has shown great promise. However, mechanistic insight remains largely unexplored. In this work, a series of silica-supported platinum (Pt) catalysts have been prepared for NAD+ cofactor regeneration, to understand the roles of Pt particle size and structure. A turnover frequency (TOF) ‘volcano plot’ was obtained for Pt clusters in the range of 2.2–7.1 nm, with the maximum TOF (136 h−1) observed at 5.6 nm. Selective Pt site blockage with polyvinyl pyrrolidone (PVP) revealed that the significant structure sensitivity originated from the synergistic effect of under- and well-coordinated sites in size-varied Pt clusters. In addition, a facet preference was also identified, where the cofactor regeneration favoured the Pt(100) surface more than Pt(111). These findings provide the first insight into NAD+ regeneration using heterogeneous Pt catalysts, which will be particularly useful for the rational design of supported metal catalysts.
研究领域:
催化化学
·
生物无机化学
·
纳米材料
·
生物催化
·
可持续化学
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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）