Toxins
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2021
·Vol. 13
·期 12
·874
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IF 4.546
Quancheng Liu,Fuchang Li,Libo Huang,Wenjie Chen,Zhongyuan Li,Chunyang Wang
Fumonisin B1(FB1) is the most common food-borne mycotoxin produced by theFusariumspecies, posing a potential threat to human and animal health. Pigs are more sensitive to FB1ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain–gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB1group was supplemented with FB1at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB1group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB1can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB1. After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB1were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB1by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.Keywords:fumonisin B1;carboxylesterase FumDSB;hypothalamus;jejunum;brain-gut peptide;ghrelin;obestatin;growing pigsKey Contribution:In this study, the effects of carboxylesterase FumDSB on appetite-related brain-gut peptides in both the hypothalamus and the jejunum of growing pigs were evaluated; next, the mechanism and safety of FumDSB was explored from the perspective of brain–gut regulation, which provided a research basis for the application of FumDSB in actual production.
研究领域:
兽医学
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毒理学
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分子生物学
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动物营养
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Jiuyang Ding,Baofei Sun,Yingdong Gao,Juan Zheng,Changyou Liu,Jian Huang,Nannan Jia,Xianglin Pei,Xueyu Jiang,Shanshan Hu,Bing Xia,Yunle Meng,Zhuihui Dai,Xiaolan Qi,Jiawen Wang
It has been shown that exposure to hexavalent Chromium, Cr (Ⅵ), via nasal cavity can have neurotoxicological effects and induces behavioral impairment due to the fact that blood brain barrier (BBB) does not cover olfactory bulb. But whether Cr (Ⅵ) can cross the BBB and have a toxicological effects in central nervous system (CNS) remains unclear. Therefore, we investigated the effects of Cr (Ⅵ) on mice treated with different concentrations and exposure time (14 days and 28 days) of Cr (Ⅵ) via intraperitoneal injection. Results revealed that Cr accumulated in hypothalamus (HY) in a timely dependent manner. Much more severer neuropathologies was observed in the group of mice exposed to Cr (Ⅵ) for 28 days than that for 14 days. Gliosis, neuronal morphological abnormalities, synaptic degeneration, BBB disruption and neuronal number loss were observed in HY. In terms of mechanism, the Nrf2 related antioxidant stress signaling dysfunction and activated NF-κB related inflammatory pathway were observed in HY of Cr (Ⅵ) intoxication mice. And these neuropathologies and signaling defects appeared in a timely dependent manner. Taking together, we proved that Cr (Ⅵ) can enter HY due to weaker BBB in HY and HY is the most vulnerable CNS region to Cr (Ⅵ) exposure. The concentration of Cr in HY increased along with time. The accumulated Cr in HY can cause BBB disruption, neuronal morphological abnormalities, synaptic degeneration and gliosis through Nrf2 and NF-κB signaling pathway. This finding improves our understanding of the neurological dysfunctions observed in individuals who have occupational exposure to Cr (Ⅵ), and provided potential therapeutic targets to treat neurotoxicological pathologies induced by Cr (Ⅵ).
研究领域:
神经科学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
CARBON
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2022
·
IF 11.307
Shiyu Yang,Zhiqiong Chen,Ping Zhou,Jiashan Xia,Tao Deng,Chao Yu
Compared with visible fluorescence carbon dots (CDs), the multi-emission (visible and near infrared) fluorescence CDs based platform (V-N Platform) with blood-brain barrier penetration, real-time brain imaging and drug loading capacities, is of great significance. Herein, a novel type of multi-emission fluorescence CDs (GT) was created to penetrate BBB for brain imaging and local drug delivery, which was synthesized by hydrothermal method, using endogenous l -tryptophan and d -glucose. The capability for in vitro imaging was verified through the experiments on cell imaging. Moreover, the ability of in vivo imaging, especially for brain imaging, was confirmed by experiments in mice and zebrafish. In addition, the in vitro and in vivo experiments preliminarily confirmed its potential to act as a drug delivery platform. This V-N Platform (GT) will be expected to have a significant impact on the researches for CDs and the theranostics of brain diseases.
研究领域:
纳米技术
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神经科学
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生物医学工程
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材料科学
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产品关联
DOI
高影响因子
BRAIN RESEARCH BULLETIN
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2022
·
IF 3.715
Xiaohui Xia,Shuai Wang,Lirong Wu,Guoxing Li,Kaiwen Hou,Anyong Yu,Zhao Yang
Background Intracerebral hemorrhage (ICH) is a serious disease with high mortality and morbidity, and effective treatment is limited. A large amount of evidence suggests that the inflammatory response contributes to secondary brain damage following ICH. TIPE2 is an essential negative regulator of both innate and adaptive immunity, and depletion of TIPE2 causes inflammatory disease. However, the possible role of TIPE2 following ICH has not been reported. Methods In this study, we investigated TIPE2 levels and inflammation in microglia treated with erythrocyte lysate in vitro. In addition, we analyzed the role of Bcl-2/Bax/cleaved caspase-3 apoptotic pathways in ICH mice. Furthermore, we observed proinflammatory cytokine production, BBB disruption, cerebral water content and neurological damage in ICH mice. Results We found that TIPE2 levels were significantly decreased in erythrocyte lysate-treated microglia compared to control microglia.Upregulation of TIPE2 decreased microglia activation and cytokine production and accelerated brain damage in ICH mice. Furthermore, upregulation of TIPE2 decreased the higher ratio of Blc-2/Bax and increased cleaved caspase-3 levels in ICH mice. In addition, upregulation of TIPE2 attenuated proinflammatory cytokine production, BBB disruption, and severe brain inflammation after ICH. Conclusion These results demonstrated that TIPE2 was negatively correlated with the pathogenesis of ICH, which prevented brain injury and attenuated deleterious inflammatory responses following ICH. TIPE2 might serve as a novel target for ICH therapy.
研究领域:
神经科学
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分子生物学
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病理学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Biophotonics
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2024
·
IF 2
Zengjun Xie,Zhihui He,Zhen Yuan,Miao Wang,Feifan Zhou
Cerebral lymphatic drainage is an important pathway for metabolic waste clearance in the brain, which plays a crucial role in the progression of central nervous system diseases. Recent studies have shown that norepinephrine (NE) is involved in the regulation of cerebral lymphatic drainage function, but the modulation mechanism remains unknown. In this study, we confirmed that NE rapidly reduced glymphatic influx and enhanced meningeal lymphatic clearance. Moreover, the transverse sinus (TS) was the vital region of cerebral lymphatic drainage regulation by NE. Further analysis revealed that NE inhibition could simultaneously enhance glymphatic drainage and dorsal meningeal lymphatic drainage, mainly acting on the TS region. This study demonstrated that the cerebral lymphatic drainage system can be regulated by NE, with the TS region serving as the primary modulating site. The findings provide a potential regulatory target for the amelioration of neurological diseases associated with cerebral lymphatic drainage function.
研究领域:
神经科学
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药理学
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神经病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
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2020
·Vol. 26
·期 1
·1-14
·
IF 4.096
Sun Xiaowei,Liu Hao,Sun Zhongren,Zhang Beng,Wang Xinyu,Liu Tingting,Pan Tingting,Gao Ying,Jiang Xicheng,Li Hongtao
Background Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia–reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms.Methods Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), and Qubin (GB7) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined.Results Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury.Conclusion sOur findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.
研究领域:
神经科学
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中医
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药理学
✓ 已验证
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
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2023
·
IF 4.6
Pandi Chen,Fenglong Li,Guyue Wang,Binbin Ying,Chao Chen,Ying Tian,Maosong Chen,Kyung Jin Lee,Wu Bin Ying,Jin Zhu
The dura mater is the final barrier against cerebrospinal fluid leakage and plays a crucial role in protecting and supporting the brain and spinal cord. Head trauma, tumor resection and other traumas damage it, requiring artificial dura mater for repair. However, surgical tears are often unavoidable. To address these issues, the ideal artificial dura mater should have biocompatibility, anti-leakage, and self-healing properties. Herein, this work has used biocompatible polycaprolactone diol as the soft segment and introduced dynamic disulfide bonds into the hard segment, achieving a multifunctional polyurethane (LSPU-2), which integrated the above mentioned properties required in surgery. In particular, LSPU-2 matches the mechanical properties of the dura mater and the biocompatibility tests with neuronal cells demonstrate extremely low cytotoxicity and do not cause any negative skin lesions. In addition, the anti-leakage properties of the LSPU-2 are confirmed by the water permeability tester and the 900 mm H 2 O static pressure test with artificial cerebrospinal fluid. Due to the disulfide bond exchange and molecular chain mobility, LSPU-2 could be completely self-healed within 115 min at human body temperature. Thus, LSPU-2 comprises one of the most promising potential artificial dura materials, which is essential for the advancement of artificial dura mater and brain surgery.
研究领域:
生物材料
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神经外科
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Nano Energy
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2021
·
IF 17.881
Guangyou Yang,Yong Tang,Tao Lin,Tianyan Zhong,Yaowei Fan,Yan Zhang,Lili Xing,Xinyu Xue,Yang Zhan
The traditional methods of detecting and adjusting blood glucose concentration, such as blood analysis and insulin injection, may delay the treatment of metabolic disease . Here, a new self-powered closed-loop brain-machine-interface system for real-time detecting and rapidly adjusting blood glucose concentration has been fabricated. The system can work without external power supply and be self-powered by the body motion itself, which can meet the requirement of immediate treatment. The system mainly consists of active blood glucose sensor, energy harvester , micro-control unit and brain stimulator . The blood glucose sensor made of enzyme/ZnO nanowire arrays can output piezoelectric voltage under the driving of body motion, and the output can be treated as the glucose-detecting signal through the biosensing-piezoelectric coupling effect. A piezoelectric ceramic device as the energy harvester can convert the body mechanical energy into electricity for powering the whole system. The micro-control unit outputs brain stimulation pulse to the dorsomedial part of the ventromedial hypothalamus (VMHdm) in the brain upon abnormal blood glucose concentration . In mouse samples, the brain stimulator connected to the VMHdm augments the expression of regulatory nerve receptors to achieve rapid increase of blood glucose concentration (39% within 10 min). Thus, a closed loop is formed among the body, brain and system. This self-powered closed-loop approach improves the accessibility of physiological insights and extends brain-machine-interface application in precision medicine for metabolic diseases.
研究领域:
生物医学工程
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代谢病学
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神经工程
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转化医学
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糖尿病研究
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分子传感
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可穿戴设备
✓ 已验证
DOI
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Runzhi Chen,Ying Xu,Peng Wu,Hao Zhou,Yi Lasanajak,Yingying Fang,Lan Tang,Ling Ye,Xing Li,Zheng Cai,Jie Zhao
The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus , and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.
研究领域:
神经病学
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胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
·
IF 4.845
Fangyuan Wang,Zhuanzhuan Yang,Mengli Liu,Yaotian Tao,Zhenbao Li,Zonghao Wu,Shuangying Gui
A rotigotine (ROT)-loaded polymer micelles thermosensitive gel (ROT-PM-TSG) delivery system was engineered to enhance the solubility of the drug, prolong the residence time, and increase the concentration of the drug in the brain tissue. First, ROT-loaded polymer micelles (ROT-PM) were tailored and optimized. The average particle size, encapsulation efficiency, and drug loading of the ROT-PM were (88.62 ± 1.47) nm , (93.5 ± 0.79) %, and (19.9 ± 0.60) %. The optimal ROT-PM-TSG formulation contained 22% P407 and 2% P188 with a gelation temperature of about 32.3 °C and a pH of 5.186. In vivo , the MRT of ROT-PM and ROT-PM-TSG nasal administration was 1.43 and 1.79 times extended than that of the intravenous. In comparison with the intravenous group, the distribution of ROT in olfactory bulb, cerebrum , cerebellum and striatum was 276.6%, 170.5%, 166.5% and 184.4%, respectively. In conclusion, the ROT-PM-TSG system has proven to be a potential application prospect as a ROT nose-to-brain delivery system.
研究领域:
药剂学
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药物递送系统
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神经药理学
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产品关联
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Yue Xin,Tianyue Guan,Guanglu Wang,Yannan Xiang,Mengxin Li,Yikun Zhao,Panpan Zhao
Sepsis is a severe systemic infection that leads to multiple organ dysfunction and high mortality, making it one of the primary causes of death in ICU patients. Sepsis also induces septic encephalopathy (SAE), resulting in acute and long-term cognitive impairments. Research indicates that inhibiting BBB damage, anti-inflammatory, and antioxidant responses are critical therapeutic directions for SAE. Monotropein (Mon), the main active component of the traditional Chinese medicine Epimedium, possesses various pharmacological effects, including antioxidant properties. This study aims to explore the protective effects and potential targets of Mon in SAE. Firstly, the GEO database was utilized to screen for highly expressed genes, identifying matrix metalloproteinase-9 (MMP9) as a target. Drug target reverse screening using Schrodinger software confirmed MMP9 as a potential therapeutic target for Mon. Subsequently, in vitro experiments using an LPS-stimulated BV-2 and HUVECs co-culture model examined the interaction between Mon and MMP9. A CLP-induced mouse model was employed to investigate Mon's role in SAE. Results indicate that MMP9 is highly expressed in SAE and promotes its progression. Mon targets MMP9, enhancing its protein stability and exerting anti-inflammatory, improved vascular permeability, and barrier protective effects. Mon alleviates brain tissue damage, BBB disruption, and synaptic loss induced by CLP, increases antioxidant enzyme activity to eliminate ROS, and suppresses sepsis-induced oxidative stress, thereby mitigating CLP-induced cognitive impairment in mice. In conclusion, Mon targets MMP9, exerting anti-inflammatory, antioxidant, and barrier protective effects, alleviating SAE. Mon may serve as a potential natural therapeutic agent for treating sepsis-induced brain dysfunction.
研究领域:
药理学
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神经科学
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免疫学
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生物信息学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NATURE MEDICINE
·
2025
·
IF 50
He Xiaolong,Hu Mengyao,Xu Yi,Xia Fangbo,Tan Yang,Wang Yuqing,Xiang Huiling,Wu Hao,Ji Tengfei,Xu Qian,Wang Lei,Huang Zhenhe,Sun Meiling,Wan Yu,Cui Peng,Liang Shaocong,Pan Yuan,Xiao Siyu,He Yan,Song Ruixin,Yan Junqing,Quan Xin,Wei Yingge,Hong Changze,Liao Weizuo,Li Fuli,El-Omar Emad,Chen Jinjun,Qi Xiaolong,Gao Jie,Zhou Hongwei
Up to 50–70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut–brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus , increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus . Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut–liver–brain axis and identify a promising therapeutic and predictive target for HE.
研究领域:
胃肠病学
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微生物学
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神经科学
✓ 已验证
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）