Frontiers in Psychiatry
·
2023
·
IF 4.7
Zhang Yanjie,Sun Yajun,Miao Qin,Guo Shilong,Wang Qi,Shi Tianyuan,Guo Xinsheng,Liu Shuai,Cheng Guiding,Wang Chuansheng,Zhang Ruiling
Objective: Alcohol dependence (AD) is a chronic recurrent mental disease caused by long-term drinking. It is one of the most prevalent public health problems. However, AD diagnosis lacks objective biomarkers. This study was aimed to shed some light on potential biomarkers of AD patients by investigating the serum metabolomics profiles of AD patients and the controls.Methods: Liquid chromatography-mass spectrometry (LC–MS) was used to detect the serum metabolites of 29 AD patients (AD) and 28 controls. Six samples were set aside as the validation set (Control: n = 3; AD group: n = 3), and the remaining were used as the training set (Control: n = 26; AD group: n = 25). Principal component analysis (PCA) and partial least squares discriminant analysis (PCA-DA) were performed to analyze the training set samples. The metabolic pathways were analyzed using the MetPA database. The signal pathways with pathway impact >0.2, value of p <0.05, and FDR < 0.05 were selected. From the screened pathways, the metabolites whose levels changed by at least 3-fold were screened. The metabolites with no numerical overlap in their concentrations in the AD and the control groups were screened out and verified with the validation set.Results: The serum metabolomic profiles of the control and the AD groups were significantly different. We identified six significantly altered metabolic signal pathways, including protein digestion and absorption; alanine, aspartate, and glutamate metabolism; arginine biosynthesis; linoleic acid metabolism; butanoate metabolism; and GABAergic synapse. In these six signal pathways, the levels of 28 metabolites were found to be significantly altered. Of these, the alterations of 11 metabolites changed by at least 3-fold compared to the control group. Of these 11 metabolites, those with no numerical overlap in their concentrations between the AD and the control groups were GABA, 4-hydroxybutanoic acid, L-glutamic acid, citric acid and L-glutamine.Conclusion: The metabolite profile of the AD group was significantly different from that of the control group. GABA, 4-hydroxybutanoic acid, L-glutamic acid, citric acid, and L-glutamine could be used as potential diagnostic markers for AD.
研究领域:
心理健康
·
代谢组学
·
药理学
·
临床化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2024
·
IF 5.5
Zhiyi Wang,Yu Yan,Wenxin Chen,Zhiping Tan,Qingfeng Yan,Qingqing Chen,Xue Ding,Jiahua Shen,Min Gao,Yang Yang,Lulu Yu,Fuzhi Lin,Yong Fu,Xiaoqiang Jin,Xiaohua Yu
Sensorineural deafness is a hearing impairment resulting from damage to the auditory nerve or inner ear hair cells. Currently, cochlear implants (CIs) are widely used as hearing aids for sensorineural deafness patients. A fundamental limitation of cochlear implants (CIs) is that spiral ganglion neurons (SGNs) cannot be replenished. This greatly restricts the rehabilitation of sensorineural deafness. Additionally, the insertion of CIs can cause secondary cochlear damage, worsening the condition of the patients' cochlear. Therefore, a new type of neural stem cells (NSCs) loaded graphene oxide-polyaniline/GelMA (GO-PAni/GelMA) conductive hydrogel electrode for cochlear implant was fabricated via in-situ radical polymerization and cyclic UV curing technique. On the one hand, the hydrogel electrode, as a direct contact layer, helps to avoid the physical hurt for cochlear. On the other hand, NSCs were supplemented via the hydrogel carrier and neuronal differentiation was induced by electrical stimulation, which was validated by the experimental results of immunofluorescence, Phalloidin Staining and RT-qPCR. Furthermore, based on RNA sequencing and transcriptome analysis, we hypothesized that the neuronal differentiation of NSCs was adjusted by the calcium signaling pathway and GABAergic synapse. Overall, our cell loading conductive hydrogel electrode may be an effective solution to sensorineural deafness. The revelation of the mechanism of neuronal differentiation promoted by electrical stimulation provides a basis for further sensorineural deafness treatment using conductive hydrogel CI electrode.
研究领域:
生物医学工程
·
神经科学
·
材料科学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular Neuroscience
·
2020
·
IF 3.921
Xu Yi,Zhang Shuai,Sun Qiang,Wang Xu-Qiao,Chai Ya-Ni,Mishra Chandan,Chandra Shah Ram,Ai Jing
Chronic cerebral hypoperfusion (CCH) is considered a preclinical condition of mild cognitive impairment and thought to precede dementia. However, as the principal cholinergic source of hippocampus, whether the septo-hippocampal neurocircuit was impaired after CCH is still unknown. In this study, we established the CCH rat model by bilateral common carotid artery occlusion (2VO). Under anesthesia, the medial septum (MS) of rats was stimulated to evoke the field excitatory post-synaptic potential (fEPSP) in the pyramidal cell layer of dCA1. Consequently, we observed decreased amplitude of fEPSP and increased paired-pulse ratio (PPR) after 8-week CCH. After tail pinch, we also found decreased peak frequency and shortened duration of hippocampal theta rhythm in 2VO rats, indicating the dysfunction of septo-hippocampal neurocircuit. Besides, by intracerebroventricularly injecting GABAergic inhibitor (bicuculline) and cholinergic inhibitors (scopolamine and mecamylamine), we found that CCH impaired both the pre-synaptic cholinergic release and the post-synaptic nAChR function in MS–dCA1 circuits. These results gave an insight into the role of CCH in the impairment of cholinergic MS–dCA1 neurocircuits. These findings may provide a new idea about the CCH-induced neurodegenerative changes.
研究领域:
神经科学
·
认知障碍
·
痴呆症
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2022
·
IF 5.78
Xueyun Wang,Jing Wu,Wang Wang,Yuanwang Zhang,Dixin He,Boying Xiao,Haohao Zhang,Anqi Song,Ying Xing,Bo Li
Cell replacement is a promising approach for neurodegenerative disease treatment. Somatic cells such as fibroblasts can be induced to differentiate into neurons by specific transcription factors; however, the potential of viral vectors used for reprogramming to integrate into the genome raises concerns about the potential clinical applications of this approach. Here, we directly reprogrammed rat embryonic skin fibroblasts into induced neurons (iNs) via six small-molecule compounds (SMs) (VPA, CHIR99021, forskolin, Y-27632, Repsox, and P7C3-A20). iNs exhibit typical neuronal morphology, and immunofluorescence showed that more than 96% of the iNs expressed the early neuronal marker class III beta-tubulin (TUJ1) and that more than 91% of iNs expressed the mature neuronal marker neuron-specific enolase (NSE) after 10 days of reprogramming. Quantitative real-time polymerase chain reaction also showed that most iNs expressed the dopaminergic neuron marker tyrosine hydroxylase, the neural marker Nur correlation factor 1, the (γ-aminobutyric acid, GABA) GABAergic neuronal marker GABA, and the cholinergic neuron marker choline acetyltransferase. In addition, we found that cell proliferation decreased during reprogramming and that protein synthesis increased initially and then decreased. SMs were mixed with hydrogels, and the hydrogels were implanted subcutaneously into the backs of rats. After 7 days, the TUJ1 and NSE proteins were expressed in surrounding tissues, indicating that SMs caused reprogramming in vivo. In summary, rat skin fibroblasts can be efficiently reprogrammed into iNs by SMs in vitro and in vivo.
研究领域:
神经科学
·
细胞生物学
·
药理学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENZYME AND MICROBIAL TECHNOLOGY
·
2023
·
IF 3.4
Fangfang Chang,Yuheng Wang,Jie Zhang,Tao Tu,Huiying Luo,Huoqing Huang,Yingguo Bai,Xing Qin,Yaru Wang,Bin Yao,Yuan Wang,Xiaolu Wang
γ-Aminobutyric acid (GABA) has been widely used in the food, feed, pharmaceutical, and chemical industry fields. Previously, we developed a whole-cell catalyst capable of converting L-glutamate (L-Glu) into GABA by overexpressing the glutamate decarboxylase gene ( gadz11 ) from Bacillus sp. Z11 in Escherichia coli BL21(DE3). However, to enhance cell permeability , a freeze-thaw treatment is required, and to enhance GADZ11 activity, pyridoxal 5′-phosphate (PLP) must be added to the reaction system. The aim of this study is to provide a more efficient approach for GABA production by engineering the recombinant E. coli above. First, the inducible expression conditions of the gadz11 in E. coli were optimized to 37 °C for 6 h. Next, an ideal engineered strain was produced via increasing cell permeability by overexpressing sulA and eliminating PLP dependence by constructing a self-sufficient system. Furthermore, an efficient whole-cell biocatalytic process was optimized. The optimal substrate concentration , cell density, and reaction temperature were 1.0 mol/L (the molecular ratio of L-Glu to L-monosodium glutamate (L-MSG) was 4:1), 15 and 37 °C, respectively. Finally, a whole-cell bioconversion procedure was performed in a 3-L bioreactor under optimal conditions. The strain could be reused for at least two cycles with GABA yield, productivity and conversion ratio of 206.2 g/L, 117.8 g/L/h and 100.0%, respectively. This is currently the highest GABA productivity from a mixture of L-Glu and L-MSG reported without the addition of cofactors or additional treatment of cells. This work demonstrates that the novel engineered E. coli strain has the potential for application in large-scale industrial GABA production.
研究领域:
生物技术
·
微生物学
·
生物化工
·
代谢工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2022
·
IF 6.058
Ting-Ting Cao,Huan Chen,Mao Pang,Si-Si Xu,Hui-Quan Wen,Bin Liu,Li-Min Rong,Mang-Mang Li
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 10 6 hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs – low (0.25 × 10 6 cells/kg), medium (1 × 10 6 cells/kg) and high (4 × 10 6 cells/kg) – on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABA A ) receptor expression by the effective doses indicates that GABA A receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 10 6 hUC-MSCs/kg is an alternative approach for treating subacute SCI.
研究领域:
干细胞治疗
·
神经科学
·
脊髓损伤
·
细胞生物学
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Jiarui Zeng,Feibi Sheng,Xi Hu,Zhenfeng Huang,Xiaofei Tian,Zhenqiang Wu
Brewer's spent grain (BSG) is the main byproduct of the beer industry and is commonly used as a low-value animal feed or food ingredient. This study investigated the role of symbiotic fermentation with Bacillus velezensi s and Levilactobacillus brevis in improving the nutritional value of BSG. The addition of B. velezensis increased the cell growth of L. brevis by over thirty-fold higher than that in the single-strain system. Simultaneously, cellulase and protease activities were substantially increased, and more soluble sugars were produced. Total amino acid, glutamic acid , and γ -aminobutyric acid (GABA) levels increased by 52.2%, 155.1%, and 144.1%, respectively. Conversely, lactic acid production decreased. Genetic analysis showed that the glycolysis-related gene pykA , pentose phosphate pathway gene gnd , and GABA-related gene gad were upregulated, while the heterolactin-related gene xpkA was downregulated, explaining that B. velezensis might inhibit heterolactin fermentation while enhancing GABA biosynthesis . This study provides a potential strategy for the high-value utilization of BSG in the food or feed industry.
研究领域:
食品科学
·
微生物学
·
生物技术
·
营养学
✓ 已验证
产品关联
DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Han Yu,Zhang Jia-qi,Ji Ya-wei,Luan Yi-wen,Li Shu-yi,Geng Hui-zhen,Ji Ying,Yin Cui,Liu Su,Zhou Chun-yi,Xiao Cheng
Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-β-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.
研究领域:
神经科学
·
疼痛研究
·
药理学
·
神经生理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Bian Zhenhua,Zhang Wenming,Tang Jingyue,Fei Qianqian,Hu Minmin,Chen Xiaowei,Su Lianlin,Fei Chenghao,Ji De,Mao Chunqin,Tong Huangjin,Yuan Xiaohang,Lu Tulin
Purpose: This study aimed to investigate the potential mechanisms and related bioactive components of ZSS for the treatment of insomnia.Method: The insomnia model of rat induced by PCPA was established. After oral administration of ZSS extract, the general morphological observation, pentobarbital sodium-induced sleep test and histopathological evaluation were carried out. Network pharmacology, assisted by UHPLC-Q-Exactive-MS/MS analysis, was developed to identify the targets of ZSS in the treatment of insomnia, as well as the corresponding signaling pathways. In addition, we validated the identified targets and pathways by RT-qPCR and immunohistochemical analysis.Results: The pentobarbital sodium-induced sleep test, determination of 5-HT and GABA levles in hypothalamic tissues and HE staining showed that ZSS extract was an effective treatment for insomnia. Network pharmacology analysis identified a total of 19 candidate bioactive ingredients in ZSS extract, along with 433 potentially related targets. Next, we performed protein-protein interaction (PPI), MCODE clustering analysis, GO functional enrichment analysis, KEGG pathway enrichment analysis, and ingredient-target-pathway (I-T-P) sub-networks analysis. These methods allowed us to investigate the synergistic therapeutic effects of crucial pathways, including the serotonergic and GABAergic synapse pathways. Our analyses revealed that palmitic acid, coclaurine, jujuboside A, N-nornuciferine, caaverine, magnoflorine, jujuboside B, and betulinic acid, all played key roles in the regulation of these crucial pathways. Finally, we used the PCPA-induced insomnia in rats to validate the data generated by network pharmacology; these in vivo experiments clearly showed that pathways associated with the serotonergic and GABAergic system were activated in the rats model. Furthermore, ZSS treatment significantly suppressed high levels of HTR1A, GABRA1, and GABRG2 expression in the hypothalamus and reduced the expression levels of HTR2A.Conclusion: Based on the combination of comprehensive network pharmacology and in vivo experiments, we successfully identified the potential pharmacological mechanisms underlying the action of ZSS in the treatment of insomnia. The results provide a theoretical basis for further development and utilization of ZSS, and also provide support for the development of innovative drugs for the treatment of insomnia.
研究领域:
药理学
·
神经科学
·
中医药
✓ 已验证
DOI
PubMed
高影响因子
PLANT SCIENCE
·
2021
·
IF 4.729
Zhengke Zhang,Jialiang Liu,Donald J. Huber,Hongxia Qu,Ze Yun,Taotao Li,Yueming Jiang
Litchi fruit has high commercial value on the international market, but senesces rapidly after harvest. We used weighted gene co-expression network analysis (WGCNA) and degradome technology to investigate the molecular mechanisms of melatonin-mediated delay of litchi fruit senescence through application of exogenous melatonin and p-chlorophenylalanine (p-CPA, an inhibitor of melatonin biosynthesis) treatments. Results demonstrated that exogenous melatonin treatment delayed litchi fruit senescence while p-CPA accelerated senescence. Coupled analyses of transcriptome and physiological parameters of litchi fruit provided the correlation of network modules with dynamic changes in browning index during storage. Additionally, we found that microRNAs (miR858 and miR160a) and their targets were actively involved in melatonin-mediated delay of litchi fruit senescence. Melatonin treatment decreased abscisic acid (ABA) content but increased PP2C and F-box expression levels, suggesting the involvement of ABA signaling in melatonin-mediated antisenescence. The transcriptions of ZAT, NAC and DREB1 were activated by melatonin treatment. Moreover, the major functional genes involved in histone methylation, γ-aminobutyric acid (GABA) metabolism, energy production, reactive oxygen species (ROS) accumulation and cell death were identified in the melatonin-inhibited litchi pericarp browning. Taken together, we first constructed the global map of the important regulators and pathways to delay litchi senescence and pericarp browning mediated by melatonin.
研究领域:
植物学
·
遗传学
·
分子生物学
·
植物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Yajing Du,Hao Lin Guo,Xin Su,Mingming Guo,Bowen Li,Hua Wang,Xiaoning Gao,Qing Yuan,Yue Teng,Tao Wang,Bin Zheng
Microbial therapies have promising applications in the treatment of a broad range of diseases. However, effective colonization of the target region by therapeutic microorganisms remains a significant challenge owing to the complexity of the intestinal system. Here, we developed surface nanocoating-based universal platform (SNUP), which enabled the manipulation of controlled release and targeted colonization of therapeutic microbes in the digestive tract without the utilization of any targeting molecules. The system controlled the decomposition time of SNUP in the gut by regulating different modification layers and modification sequences on the microorganism’s surface, so that the microorganism was released at a predetermined time and space. With the SNUP nanomodification technology, we could effectively deliver therapeutic microorganisms to specific complex intestinal regions such as the small intestine and colon, and protect the bioactivity of therapeutic microorganisms from destruction by both strong acids and digestive enzymes. In this study, we found that two layers SNUP-encapsulated Liiliilactobacillus salivarius (LS@CCMC) could efficiently colonize the small intestine and significantly improve the symptoms of a mouse model of Parkinson’s disease through sustained secretion of γ-aminobutyric acid (GABA). This surface nanocoating-based universal platform system does not require the design of specific targeting molecules, providing a simple and universal method for colonized microbial therapy, target theranostics, precision medicine, and personalized medicine.
研究领域:
生物医学工程
·
药学
·
微生物学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Ye Lusha,Gao Yanan,Mok Simon Wing Fai,Liao Wucan,Wang Yazhou,Chen Changjiang,Yang Lijun,Zhang Junfeng,Shi Liyun
Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.
研究领域:
药理学
·
免疫学
·
肺科学
·
纳米技术
·
分子生物学
✓ 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）