Redox Biology
·
2025
·
IF 11.9
Chuanlin Feng,Lei Zhang,Xiaoyuan Zhou,Shiyu Lu,Ruowen Guo,Chao Song,Xin Zhang
The magnetic properties of substances directly determine their response to an externally applied magnetic field, which are closely associated with magnetoreception, magnetic resonance imaging (MRI), and magnetic bioeffects. However, people understanding of the magnetic properties of living organisms remains limited. In this study, we utilized NRF2 (nuclear factor erythroid 2-related factor 2) deficiency mice to investigate the contribution of redox (oxidation–reduction) homeostasis, in which the key process is the transfer of electron, a direct target of magnetic field and origin of paramagnetism. Our results show that the NRF2 -/- mice exhibit significantly altered systemic redox state, accompanied by increased magnetic susceptibility, particularly in the liver and spleen. Further analyses reveal that the levels of paramagnetic reactive oxygen species (ROS) in these tissues are markedly elevated compared to wild-type mice. Moreover, the concentrations of Fe 2+ and Fe 3+ are significantly elevated in NRF2 -/- mice, which are directly correlated with the increased magnetic susceptibility. The disrupted redox balance in NRF2 -/- mice not only exacerbates oxidative stress and iron deposition, but also induces impairs to the liver and spleen. The findings highlight the combined effects of ROS and iron metabolism in driving magnetic susceptibility changes, providing valuable theoretical insights for further research into magnetic bioeffects effects and organ-specific sensitivity to magnetic fields.
研究领域:
生物物理学
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分子生物学
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医学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2018
·Vol. 9
·期 8
·1-20
·
IF 5.638
Yang Qin,Zheng Fangshuo,Hu Yida,Yang Yi,Li Yun,Chen Guojun,Wang Wei,He Miaoqing,Zhou Ruijiao,Ma Yuanlin,Xu Demei,Tian Xin,Gao Xiaoya,Wang Qing,Wang Xuefeng
Epilepsy is one of the most prevalent and drug-refractory neurological disorders. Zinc finger DHHC-type containing 8 (ZDHHC8) is a putative palmitoyltransferase that is highly expressed in the brain. However, the impact of ZDHHC8 on seizures remains unclear. We aimed to explore the association of ZDHHC8 with epilepsy and investigate its in epileptogenesis in in vivo and in vitro models through behavioral, electrophysiological, and pathological studies. We used kainic acid- and pilocarpine-induced C57BL/6 mice and magnesium-free-induced pyramidal neurons as experimental epileptic models in this study. We first found increased ZDHHC8 expression in the brains of temporal lobe epilepsy (TLE) patients, similar to that observed in chronic epileptic mice, strongly suggesting that ZDHHC8 is correlated with human epilepsy. In the in vitro seizure models, knocking down ZDHHC8 using recombinant adeno-associated virus (rAAV) delayed seizure precipitation and decreased chronic spontaneous recurrent seizures (SRSs) and epileptiform-like discharges, while ZDHHC8 overexpression had the opposite effect. ZDHHC8 levels were consistent with seizure susceptibility in induced mice with SRSs. In an in vitro magnesium-free model, neuronal hyperexcitability and hypersynchrony were reduced in ZDHHC8-knockdown neurons but were increased in ZDHHC8-overexpressing neurons. To further explore the potential mechanisms, we observed that ZDHHC8 had a significant modulatory effect on 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor-related excitatory, but not inhibitory, glutamatergic synaptic neurotransmission, further affecting the inward rectification of AMPA currents in acute hippocampal slices in whole-cell recordings. ZDHHC8 facilitated GluA1 trafficking to the neuronal surface in the hippocampus, as shown by immunoprecipitation and Western blotting. These results suggest that ZDHHC8 may promote the generation and propagation of seizures in humans and that knocking down ZDHHC8 might produce anti-epileptogenic effects in drug-resistant epilepsy. Our study provides evidence that may facilitate the development of an alternative approach for the treatment of epilepsy by modulating AMPA/GluA1-mediated neurotransmission.
研究领域:
神经科学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2025
·
IF 8.4
Wang Hao,Zhang Li,Yang Wan-yue,Ji Xiao-yi,Gao An-qi,Wei Yi-hong,Ding Xin,Kang Yue,Ding Jian-hua,Fan Yi,Lu Ming,Hu Gang
Obesity increases the risk of depression. Evidence shows that peripheral inflammation, glycemic dysregulation, and hyperactivity within the hypothalamic-pituitary-adrenal axis are implicated in both obesity and depression. In this study we investigated the impact of visceral adipose tissue (VAT), a crucial characteristic of obesity, on stress susceptibility in obese mice. Age-matched mice were fed with chow diet (CD) or high-fat diet (HFD), respectively, for 12 weeks. CD mice were deprived of VAT and received transplantation of VAT from HFD mice (TransHFD) or CD mice (TransCD). Extracellular vesicles (EVs) were prepared from VAT of CD or HFD mice, and intravenously injected (100 μg, 4 times in 2 weeks) in naïve mice or injected into hippocampus (5 μg, 4 times in 2 weeks) through implanted bilateral cannula. Depression-like behaviors were assessed 14 days after transplantation. We showed that HFD mice exhibited significantly higher body weight gain and impaired insulin and glucose tolerance, accompanied by increased stress susceptibility. Transplantation of VAT or VAT-derived EVs from HFD mice caused synaptic damage and promoted stress susceptibility in recipient mice. Through inhibiting miRNA biogenesis in the VAT and miRNA sequencing analysis, we demonstrated that miR-140-5p was significantly upregulated in both VAT-EVs and hippocampus of HFD mice. Overexpression of hippocampal miR-140-5p in naïve mice not only facilitated acute stress-induced depression-like behaviors, but also decreased hippocampal CREB-BDNF signaling cascade and synaptic plasticity. Conversely, knockdown of miR-140-5p in the VAT, VAT-EVs or hippocampus of HFD mice protected against acute stress, reducing stress susceptibility that were mediated via CREB-BDNF pathway. In summary, VAT-EVs or the cargo miRNAs in obese mice promote synaptic damage and stress susceptibility, providing potential therapeutic targets for metabolism-related affective disorders.
研究领域:
医学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Yue Cao,Shouchun Xiao,Bingying He,Xinlei Shi,Nan Xiao,Xueke Liu,Donghui Liu,Zhiqiang Zhou,Peng Wang
Fluxapyroxad is the most commonly used succinate dehydrogenase inhibitor fungicide. This work investigated its adverse effects on colitis susceptibility and explored the underlying mechanisms based on a mouse model. After 13 weeks of exposure at the acceptable daily intake (ADI) level, fluxapyroxad exacerbated the susceptibility to colitis, impaired the intestinal barrier, and elevated proinflammatory cytokines and chemokines of the colon in mice. It was found that this toxic effect was caused by the disruption of the gut microbiome. Specifically, the abundance of Lachnospiraceae and Muribaculaceae decreased, while Desulfovibrionaceae and Eggerthellaceae increased. Altered microbiota reduced fecal indole derivatives, including indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), and indole-3-acrylic acid (IArA), inhibiting aryl hydrocarbon receptor (AHR) activation, disrupting immune homeostasis by overactivating Th17 cells and insufficient Treg cell differentiation, and causing mild colonic inflammation. Oral antibiotic-treated mice and fecal transfer experiments validated the pathway. Susceptibility to colitis induced by fluxapyroxad was not detected in the oral antibiotic-treated mice. Fecal transfer of the disordered gut microbiota caused by fluxapyroxad could aggravate the severity of colitis in recipient oral antibiotic-treated mice that did not receive fluxapyroxad exposure. In conclusion, chronic fluxapyroxad exposure at the ADI level exacerbated colitis via a gut microbiota–indole derivatives–Treg/Th17 cell balance axis, offering a new risk assessment perspective of fluxapyroxad.
研究领域:
毒理学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Nature Metabolism
·
2023
·
IF 20.8
Wang Pei,Wu Peng-Fei,Wang Hua-Jie,Liao Fang,Wang Fang,Chen Jian-Guo
Ammonia has been long recognized as a metabolic waste product with well-known neurotoxic effects. However, little is known about the beneficial function of endogenous ammonia. Here, we show that gut ammonia links microbe nitrogen metabolism to host stress vulnerability by maintaining brain glutamine availability in male mice. Chronic stress decreases blood ammonia levels by altering gut urease-positive microbiota. A representative urease-producing strain, Streptococcus thermophilus , can reverse depression-like behaviours induced by gut microbiota that was altered by stress, whereas pharmacological inhibition of gut ammonia production increases stress vulnerability. Notably, abnormally low blood ammonia levels limit the brain’s availability of glutamine, a key metabolite produced by astrocytes that is required for presynaptic γ-aminobutyric acid (GABA) replenishment and confers stress vulnerability through cortical GABAergic dysfunction. Of therapeutic interest, ammonium chloride (NH 4 Cl), a commonly used expectorant in the clinic, can rescue behavioural abnormalities and GABAergic deficits in mouse models of depression. In sum, ammonia produced by the gut microbiome can help buffer stress in the host, providing a gut–brain signalling basis for emotional behaviour.
研究领域:
神经科学
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微生物学
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精神病学
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产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Yu Cao,Yang Zhao,Tan Deng,Qigang Zhou,Gang Hu,Zhuang-Li Hu,Yan-Yi Jiang,Xiao-Han Yang,Fang Wang,Peng-Fei Wu,Jian-Guo Chen
Extensive research highlights impaired brain energy metabolism in neuropsychiatric disorders, whereas much less is known about the role of the peripheral metabolic state. The liver is the metabolic hub, and herein we demonstrate that hepatic hydrolysis of acetyl-coenzyme A, a central metabolic intermediate, signals the brain and helps buffer stress. Using a chronic social defeat stress paradigm in male mice, we observed a hepatic glucose-to-acetate metabolic switch, followed by a glucocorticoid-repressed transcription of the acetyl-coenzyme A hydrolase, acetyl-coenzyme A thioesterase 12, to confer stress vulnerability. Hepatic overexpression of acetyl-coenzyme A thioesterase 12 alleviated depression-like phenotypes via increasing acetate output to promote histone acetylation in the ventral hippocampus, which bolstered the expression of programmed cell death ligand 1 in astrocytes, limiting neuroinflammation and rescuing inhibitory synaptic transmission dysfunction. Our findings demonstrate that hepatic acetyl-coenzyme A hydrolysis serves as a key liver-brain axis component that regulates depression susceptibility.
研究领域:
神经生物学
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代谢学
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精神病学
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分子生物学
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免疫神经学
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表观遗传学
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肝脏病学
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转化医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2025
·
IF 2.9
Qiuru Chen,Yulei Liang,Yanbin Dong,Junling Cui,Kun He,Xiaoyuan Ma,Jinfeng Zhao,Yajun Zhai,Li Yuan
H-NS is a histone-like nucleoid-structuring protein that regulates gene expressions, particularly acquired foreign genes, however, little is known about whether H-NS can modulate bacterial susceptibility by regulating its intrinsic genes. The hns-deleted mutant EΔhns, the hns-complemented strain EΔhns/phns and the hns-overexpressed strain E/phns were derivatives of Escherichia coli ATCC 25922, the susceptibility of which were assessed by the broth microdilution method and time-kill curves assays. We found that the MICs for strain EΔhns against gentamicin and amikacin were significantly decreased by 8–16 folds in contrast to E. coli ATCC 25922. Further studies displayed that the absence of hns caused damage to the bacterial outer membrane and increased the expression levels of porin-related genes, such as ompC, ompF, ompG, and ompN, thus obviously enhancing aminoglycosides uptake of strain EΔhns. Meanwhile, hns deletion also led to remarkable inhibition of the efflux pumps activity and decreased expressions of efflux-related genes clbM, acrA, acrB, acrD, and emrE, which reduced the efflux of aminoglycosides. In addition, the activation of glycolysis and electron transport chain, as well as the reduction of Δψ dissipation, could lead to a remarkable increase in proton motive force (PMF), thus further inducing more aminoglycosides uptake by strain EΔhns. Our findings reveal that H-NS regulates the resistance of E. coli to aminoglycosides by influencing its uptake and efflux, which will enrich our understanding of the mechanism by which H-NS modulates bacterial resistance.
研究领域:
微生物学
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分子生物学
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抗菌素耐药性
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DOI
PubMed
高影响因子
NEUROSCIENCE
·
2025
·
IF 2.8
Viveka Chinnasamy,Carl E. Stafstrom,Li-Rong Shao
Seizures are a common comorbidity in children with Down syndrome (DS) yet seizure genesis in the DS brain is poorly understood. The two most common types of seizures in DS patients are infantile spasms (IS) and generalized tonic-clonic seizures. Using a novel humanized DS model (TcMAC21), we revealed an increased propensity to IS associated with a heightened neocortical excitation-inhibition ratio. Here, we examined the susceptibility of TcMAC21 mice to flurothyl-induced tonic-clonic type seizures and their propensity to epileptiform activity in neocortical-hippocampal slices. At postnatal day (P) 9–11, TcMAC21 mice exhibited significantly shorter latencies to flurothyl seizures but similar seizure durations compared with euploid controls. At P17-18, TcMAC21 mice showed both shorter seizure latencies and longer seizure durations than euploid mice. In neocortical-hippocampal slices, the frequency and duration of spontaneous epileptiform bursts (induced by 0 Mg 2+ and 4-aminopyridine) in hippocampal CA3 and neocortical layers II/III and V were not significantly different between the euploid and TcMAC21 mice. In addition, we assessed evoked responses in layer II/III by electrical stimulation at the junction of layer VI and white matter, in the presence of a GABA A receptor blocker, gabazine (1 uM). At P9-P13, evoked responses in layer II/III were similar between TcMAC21 and euploid mice; however, at P17-P20, the responses were significantly greater in TcMAC21 than euploid controls. Together, these data show that TcMAC21 mice exhibit heightened susceptibility to tonic-clonic seizures and an age-dependent increased neocortical excitability compared to euploid mice. These results provide new insights into the pathophysiology of seizures in DS.
研究领域:
神经科学
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发育生物学
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癫痫研究
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染色体疾病
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脑电生理学
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转化神经病学
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分子神经病理学
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DOI
PubMed
高影响因子
ZOOLOGICAL RESEARCH
·
2021
·
IF 4.56
Huan Wang,Tian-Xiu Qiu,Jian-Fei Lu,Han-Wei Liu,Ling Hu,Lei Liu,Jiong Chen
Chronic pollution in aquatic ecosystems can lead to many adverse effects, including a greater susceptibility to pathogens among resident biota. Trifloxystrobin (TFS) is a strobilurin fungicide widely used in Asia to control soybean rust. However, it has the potential to enter aquatic ecosystems, where it may impair fish resistance to viral infections. To explore the potential environmental risks of TFS, we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus (SVCV). Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge, SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini (EPC) cells and zebrafish exposed to 25 μg/L TFS. Results showed that the highest viral load was more than 100-fold that of the controls. Intracellular biochemical assays indicated that autophagy was induced by TFS, and associated changes included an increase in autophagosomes, conversion of LC3-II, accumulation of Beclin-1, and degradation of P62 in EPC cells and zebrafish. In addition, TFS markedly decreased the expression and phosphorylation of mTOR, indicating that activation of TFS may be associated with the mTOR-mediated autophagy pathway. This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.
研究领域:
环境毒理学
·
水生生物学
·
病毒学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Dun Jiang,Shuai Wu,Mingtao Tan,Hong Jiang,Shanchun Yan
Insect susceptibility to entomopathogenic microorganisms under heavy metal stress, as well as its regulatory mechanism is still poorly understood. This study aims to investigate the susceptibility of gypsy moth larvae to Beauveria bassiana under cadmium (Cd) stress (at 3.248 or 44.473 mg Cd/kg fresh food), and reveal the potential molecular mechanisms underlying the Cd effect on the larval susceptibility to B. bassiana via combined transcriptome and proteome analyses. Our results showed that pre-exposure to Cd increased the susceptibility of gypsy moth larvae to B. bassiana , and there was an additive effect between Cd exposure and B. bassiana infection on the larval mortality. Under the Cd stress at low and high concentrations, 138 and 899 differentially expressed genes (DEGs), as well as 514 and 840 differentially expressed proteins (DEPs) were identified, respectively. Immunotoxic effects induced by Cd exposure at the transcription level increased in a negative dose-response manner, with no immunity-related DEGs obtained at the low Cd concentration and a high number of immunity-related DEGs down-regulated at the high Cd concentration. In contrast, a potentially suppressed or stimulated trend in the Toll and Imd signaling pathway at protein level was revealed under low or high concentration of Cd treatment. Analysis of xenobiotics biodegradation-related pathways at both transcription and translation levels revealed that the gypsy moth larvae possessed an efficient homeostasis regulatory mechanism to the low-level Cd exposure, but exhibited a reduced xenobiotics biodegradation capability to the Cd stress at high levels. Together, these findings demonstrate Cd contamination promote the microbial-based biocontrol efficacy, and unravel the molecular regulatory network of heavy metal exposures that affects susceptibility of insects to pathogenic diseases.
研究领域:
昆虫学
·
毒理学
·
分子生物学
·
环境科学
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产品关联
DOI
PubMed
高影响因子
Cell Genomics
·
2024
·
IF 11.1
Sijia Zhang,Qiao Song,Peng Zhang,Xiaona Wang,Rong Guo,Yanyan Li,Shuai Liu,Xiaoyu Yan,Jingjing Zhang,Yiwei Niu,Yirong Shi,Tingrui Song,Tao Xu,Shunmin He
Variable number tandem repeat (VNTR) is a pervasive and highly mutable genetic feature that varies in both length and repeat sequence. Despite the well-studied copy-number variants, the functional impacts of repeat motif polymorphisms remain unknown. Here, we present the largest genome-wide VNTR polymorphism map to date, with over 2.5 million VNTR length polymorphisms (VNTR-LPs) and over 11 million VNTR motif polymorphisms (VNTR-MPs) detected in 8,222 high-coverage genomes. Leveraging the large-scale NyuWa cohort, we identified 2,982,456 (31.8%) NyuWa-specific VNTR-MPs, of which 95.3% were rare. Moreover, we found 1,937 out of 38,685 VNTRs that were associated with gene expression through VNTR-MPs in lymphoblastoid cell lines. Specifically, we clarified that the expansion of a likely causal motif could upregulate gene expression by improving the binding concentration of PU.1. We also explored the potential impacts of VNTR polymorphisms on phenotypic differentiation and disease susceptibility. This study expands our knowledge of VNTR-MPs and their functional implications.
研究领域:
基因组学
·
分子生物学
·
人类遗传学
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产品关联
DOI
PubMed
高影响因子
IMMUNOLOGY LETTERS
·
2019
·
IF 2.552
Gang Chi,Jin-hong Pei,Qin-ya Ma,Ying-Xia Ru,Zuo-hua Feng
Autoimmune hepatitis (AIH) is a chronic liver disease mediated by immunity, and could lead to liver fibrosis and hepatocellular carcinoma. However, the mechanisms for breaking hepatic tolerance and driving AIH still remain elusive. We herein reported that the non-specific liver inflammation triggered by carbon tetrachloride (CCl 4 ) recruited high numbers of CD4+T, CD8+T and B cells, and elevated the expression of proinflammaitory cytokines in Balb/c mice, further breaking liver tolerance and inducing autoimmune response, AIH inflammation and liver fibrosis in the presence of CYP2D6 antigen mimicry. In contrast, adenovirus infection could not break liver tolerance and induce AIH in Balb/c mice even in the presence of CYP2D6 antigen mimicry. These results suggested that genetic predisposition could determine liver tolerance in Balb/c mice. The chemical induced inflammation in the liver breaks tolerance and might be considered important for the initiation and development of AIH in Balb/c mice.
研究领域:
免疫学
·
肝病学
·
病理学
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产品关联
DOI
PubMed
高影响因子
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