Bioanalysis
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2025
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IF 1.8
Kaiwei Luo,Danrui Liu,Shengshuo Zhang,Xin Zhang,Qunan Cheng,Jie Lin,Yonghua Yu
Aims This study aimed to establish a robust LC-MS/MS method for quantifying trazodone in human plasma and investigate its pharmacokinetic profile in healthy Chinese subjects under fasting and fed conditions.Materials & methods A validated LC-MS/MS method using protein precipitation was applied to analyze trazodone in 68 healthy subjects (34 fasting/34 fed), with full method validation performed.Results This method exhibited high selectivity, precision, and accuracy. The results showed good linearity in the range of 5–3000 ng/mL and matrix effect results showed no matrix interference. The pharmacokinetic data revealed notable differences between the fasting and postprandial states.Conclusions The validated LC-MS/MS method proved reliable for trazodone quantification. The observed food effects on absorption suggest clinical dosing should consider administration conditions to ensure optimal therapeutic outcomes.
研究领域:
分析化学
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药理学
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临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
·
2025
·
IF 25.9
Xie Ling-Qi,Hu Biao,Lu Ren-Bin,Cheng Ya-Lun,Chen Xin,Wen Jie,Xiao Yao,An Yu-Ze,Peng Ning,Dai Yu,Xie Genqing,Guo Qi,Peng Hui,Luo Xiang-Hang
Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.
研究领域:
神经科学
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内分泌学
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代谢研究
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睡眠医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Lianxia Guo,Yifei Xiao,Zanjin Li,Yuwei Huang,Haobin Cen,Zicong Wu,Hongbo Wang,Xinyu Liu,Zhehan Yang,Caifeng Zhao,Tingying Hao,Hui Chen,Meng Jin,Danyi Lu,Min Chen,Baojian Wu
The intestinal clock plays a role in transmitting feeding signals and generating circadian events, but how this clock system may time homeostatic processes related to sleep-wake regulation is unknown. Our functional dissections of the circadian clock in intestinal epithelial cells (IECs) demonstrate that its integrity is required for maintenance of the diurnal sleep-wake cycle. In IECs, BMAL1 generates diurnal rhythmic SLC6A19 expression that promotes intestinal absorption of glutamine during the active phase, which enhances glutamatergic neuron activities in hypothalamic nuclei and contributes to increased wakefulness and decreased sleep. The involvement of glutamine homeostasis in sleep-wake regulation is also pronounced during the rest phase, as an elevation of glutamine in the rest phase caused by IEC deficiency of REV-ERBα is causally linked to sleep abnormalities characterized by reduced sleep. Overall, the intestinal clock shapes the diurnal sleep-wake cycle through temporally gating glutamine homeostasis and serves as a potential target for boosting the sleep rhythm and for managing sleep disorders.
研究领域:
时间生物学
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神经科学
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代谢学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
GENE
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2014
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IF 2.082
Tao Wu,Anqi Guo,Qingyu Shu,Yangjian Qi,Ying Kong,Zhiping Sun,Shumin Sun,Zhengwei Fu
l -Carnitine supplementation has been used to reduce obesity caused by high-fat diet, which is beneficial for lowering blood and hepatic lipid levels, and for ameliorating fatty liver. However, whether l -carnitine may affect irregular feeding-induced obesity and lipid metabolism disorder is still largely unknown. In the present study, we developed a time-delayed pattern of eating, and investigated the effects of l -carnitine on the irregular eating induced adiposity in mice. After an experimental period of 8 weeks with l -carnitine supplementation, l -carnitine significantly inhibited body weight increase and epididymal fat weight gain induced by the time-delayed feeding. In addition, l -carnitine administration decreased levels of serum alanine aminotransferase (GPT), glutamic oxalacetic transaminase (GOT) and triglyceride (TG), which were significantly elevated by the irregular feeding. Moreover, mice supplemented with l -carnitine did not display glucose intolerance-associated hallmarks, which were found in the irregular feeding-induced obesity. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that l -carnitine counteracted the negative alterations of lipid metabolic gene expression (fatty acid synthase, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase , cholesterol 7α-hydroxylase, carnitine/acylcarnitine translocase) in the liver and fat of mice caused by the irregular feeding. Therefore, our results suggest that the time-delayed pattern of eating can induce adiposity and lipid metabolic disorders , while l -carnitine supplementation might prevent these negative symptoms.
研究领域:
营养学
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代谢研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iMeta
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2025
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IF 33.2
Yihang Zhao,Mengzhen Jia,Chen Ding,Bingkun Bao,Hangqi Li,Jiabin Ma,Weixuan Dong,Rui Gao,Xuhui Chen,Jiao Chen,Xiaoshuang Dai,Yuanqiang Zou,Jun Hu,Lin Shi,Xuebo Liu,Zhigang Liu
Time-restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via the gut-brain axis remains elusive. In a clinical trial, we observed, for the first time, that a 4-month TRF ameliorated cognitive impairments among Alzheimer's disease (AD) patients. Experiments in 5xFAD mice corroborated the gut microbiota-dependent effect of TRF on mitigating cognitive dysfunction, amyloid-beta deposition, and neuroinflammation. Multi-omics integration linked Bifidobacterium pseudolongum ( B. pseudolongum ) and propionic acid (PA) with key genes in AD pathogenesis. Oral supplementation of B. pseudolongum or PA mimicked TRF's protective effects. Positron emission tomography imaging confirmed PA's blood-brain barrier penetration, while knockdown of the free fatty acid receptor 3 (FFAR3) diminished TRF's cognitive benefits. Notably, we observed a positive correlation between fecal PA and improved cognitive function in an AD cohort, further indicating that TRF enhanced PA production. These findings highlight the microbiota-metabolites-brain axis as pivotal in TRF's cognitive benefits, proposing B. pseudolongum or PA as potential AD therapies. Graphical A 4-month of time-restricted feeding (TRF) intervention alleviated cognitive impairments in Alzheimer's disease (AD) patients, while a 3-month TRF regimen improved spatial memory, reduced amyloid-beta accumulation, and promoted microglial aggregation around plaques in AD mice. Antibiotic-induced gut microbiota depletion partly abolished TRF's benefits. Through creatively integrating gut microbiota, metabolites, and hippocampal genes, Bifidobacterium pseudolongum ( B. pseudolongum ) and propionic acid (PA) were identified as key contributors to TRF's cognitive effects, with supplementation of either mimicking TRF's protective benefits. Positron emission tomography imaging revealed that PA directly crossed the blood-brain barrier, and PA supplementation restored disrupted metabolism in AD mice. Knockdown of its receptor free fatty acid receptor 3 (FFAR3) diminished TRF's protective effects. A case-control study showed a negative association between PA and cognitive status, while the TRF clinical intervention linked fecal PA to cognitive status. These findings suggest PA as a potential biomarker and underscore precise TRF-based nutritional interventions as a promising strategy for managing neurodegenerative diseases. Highlights Time-restricted feeding (TRF) improved cognitive function in Alzheimer's disease (AD) patients, with notable enhancement in executive function. Multi-omics integrated analysis in AD mice identified Bifidobacterium pseudolongum ( B. pseudolongum ) and propionic acid (PA) as key mediators of TRF's cognitive benefits. The potential molecular mechanism by which TRF alleviates cognitive impairment induced by AD involves the B. pseudolongum –PA-free fatty acid receptor 3 (FFAR3) pathway. Case-control study and TRF clinical intervention demonstrated PA as a potential biomarker for AD.
研究领域:
神经科学
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微生物学
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营养学
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分子生物学
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临床试验
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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