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1.
Sci Adv ; 10(16): eadk1855, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38630814

ABSTRACT

Transfected stem cells and T cells are promising in personalized cell therapy and immunotherapy against various diseases. However, existing transfection techniques face a fundamental trade-off between transfection efficiency and cell viability; achieving both simultaneously remains a substantial challenge. This study presents an acoustothermal transfection method that leverages acoustic and thermal effects on cells to enhance the permeability of both the cell membrane and nuclear envelope to achieve safe, efficient, and high-throughput transfection of primary T cells and stem cells. With this method, two types of plasmids were simultaneously delivered into the nuclei of mesenchymal stem cells (MSCs) with efficiencies of 89.6 ± 1.2%. CXCR4-transfected MSCs could efficiently target cerebral ischemia sites in vivo and reduce the infarct volume in mice. Our acoustothermal transfection method addresses a key bottleneck in balancing the transfection efficiency and cell viability, which can become a powerful tool in the future for cellular and gene therapies.


Subject(s)
Mesenchymal Stem Cells , Mice , Animals , Transfection , Mesenchymal Stem Cells/metabolism , Plasmids , Cell Membrane , Cell- and Tissue-Based Therapy
2.
Quant Imaging Med Surg ; 14(2): 1526-1540, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38415119

ABSTRACT

Background: Neuroimaging plays a central role in the evaluation, treatment, and prognosis of neonates. In recent years, the exploration of the developing brain has been a major focus of research for researchers and clinicians. In this study, we conducted bibliometric and visualization analyses of the related studies in the field of neonatal magnetic resonance imaging (MRI) brain neuroimaging from the past 10 years, and summarized its research status, hotspots, and frontier development trends. Methods: The Web of Science core collection database was used as the literature source from which to retrieve the relevant papers and reviews in the field of neonatal MRI brain neuroimaging published in the Science Citation Index-Expanded from 2013 to 2022. VOSviewer and CiteSpace were used to conduct bibliometric and visualization analyses of the annual publication volume, countries, institutions, journals, authors, co-cited literature, and the overall distribution of keywords. Results: We retrieved 3,568 papers and reviews published from 2013 to 2022. The number of publications increased during this period. The United States (US) and the United Kingdom were the largest contributors, with the US receiving the highest H-index and number of citations. The institutions that published the most were the University of London and Harvard University. The research mainly focused on cerebral cortex, brain tissue, brain structure network, artificial intelligence algorithm, automatic image segmentation, and premature infants. Conclusions: This study reveals the research status and hotspots of magnetic resonance imaging in the field of neonatal brain neuroimaging in the past decade, which helps researchers to better understand the research status, hotspots, and frontier development trends.

3.
Phytomedicine ; 126: 155422, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38422651

ABSTRACT

BACKGROUND: Prenatal stress (PS) can cause cognitive disorder and a range of psychological illnesses, including anxiety and depression. Icariin (ICA) has shown promising effects in improving PS-induced depressive behaviour. However, its mechanism of action remains unclear. PURPOSE: This study was performed to reveal the key targets, metabolites and gut microbiota for ICA in improving depressive behaviour in PS rat pups. METHODS: A prenatal restraint stress animal model was established for Sprague-Dawley (SD) rats in late pregnancy. Male pups were randomly divided into six groups: no stress group (NS), PS group, PS + saline group (PS_S), PS + high-dose ICA group (ICAH, 80 mg/kg*day), PS + low-dose ICA group (ICAL, 40 mg/kg*day) and PS + fluoxetine group (FLU, 10 mg/kg*day). The depressive behaviour of each group of rat pups was evaluated using open field test, forced swimming test and sucrose preference test. Different metabolites were identified using untargeted metabolomics of serum and faeces, and metabolic pathways were analyzed through MetaboAnalyst. Targets for ICA acting on depression were determined after network pharmacology was applied. An integrated network of network pharmacology and metabolomics were constructed using Cytoscape software, and molecular docking were performed to verify the interactions between ICA and key targets. Finally, gut microbiota of rat pups in each group were analyzed after 16S rDNA sequencing. RESULTS: PS could cause rat pups to exhibit depressive behaviour, and ICA could significantly improve this depressive behaviour. A total of 49 differential metabolites were found in serum and 23 differential metabolites were found in faeces, and 24 metabolites in serum and 6 metabolites in faeces could be reversed following ICA administration. Integrated analysis focused on five key targets (i.e. adenosyl homocysteinase; medium-chain specific acyl-CoA dehydrogenase, mitochondrial; thymidine phosphorylase; cGMP-specific 3',5'-cyclic phosphodiesterase and xanthine dehydrogenase/oxidase) and three metabolites (i.e. palmitoylcarnitine, methionine and hypoxanthine). Molecular docking indicated that ICA combined well with key targets. Gut microbiota analysis showed that g_Bacteroides, f_Bacteroidaceae and s_Lactobacillus reuteri were required for ICA to improve depressive behaviour. CONCLUSION: In this study, the antidepressant mechanism of ICA was clarified with a strategy of integrating metabolomics, network pharmacology and gut microbiota. ICA has a good effect on improving metabolism and increasing the abundance of probiotics in the intestine. The present research provided new insights into the anti-depressant mechanism of ICA.


Subject(s)
Flavonoids , Gastrointestinal Microbiome , Female , Rats , Male , Pregnancy , Animals , Rats, Sprague-Dawley , Molecular Docking Simulation , Network Pharmacology , Metabolomics
4.
Front Neurosci ; 17: 1146613, 2023.
Article in English | MEDLINE | ID: mdl-37152596

ABSTRACT

Background: Studies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression. Methods: In this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites (n = 24,925) and depression (n = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and "leave-one-out" methods. Results: Apolipoprotein A-I (OR 0.990, 95% CI 981-0.999) and glutamine (OR 0.985, 95% CI 0.972-0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009-1.034), glycoproteins (OR 1.005, 95% CI 1.000-1.009), isoleucine (OR 1.013, 95% CI 1.002-1.024), and urea (OR 1.020, 95% CI 1.000-1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites. Conclusion: In this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.

5.
J Cell Mol Med ; 27(12): 1697-1707, 2023 06.
Article in English | MEDLINE | ID: mdl-37165726

ABSTRACT

The skin harbours transcriptionally and functionally heterogeneous mesenchymal cells that participate in various physiological activities by secreting biochemical cues. In this study, we aimed to identify a new subpopulation of dermal mesenchymal cells that enhance hair follicle regeneration through a paracrine mechanism. Integrated single-cell RNA sequencing (scRNA-seq) data analysis revealed epidermal growth factor receptor (EGFR) as a marker of distinct fibroblast subpopulation in the neonatal murine dermis. Immunofluorescence staining and fluorescence-activated cell sorting (FACS) were used to validate the existence of the cell population in Krt14-rtTA-H2BGFP mouse. The difference of gene expression between separated cell subpopulation was examined by real-time PCR. Potential effect of the designated factor on hair follicle regeneration was observed after the application on excisional wounds in Krt14-rtTA-H2BGFP mouse. Immunofluorescence staining demonstrated the existence of dermal EGFR+ cells in neonatal and adult mouse dermis. The EGFR+ mesenchymal population, sorted by FACS, displayed a higher expression level of Igf1 (insulin-like growth factor 1). Co-localisation of IGF1 with EGFR in the mouse dermis and upregulated numbers of hair follicles in healed wounds following the application of exogenous IGF1 illustrated the contribution of EGFR+ cells in promoting wound-induced hair follicle neogenesis. Our results indicate that EGFR identifies a subpopulation of dermal fibroblasts that contribute to IGF1 promotion of hair follicle neogenesis. It broadens the understanding of heterogeneity and the mesenchymal cell function in skin and may facilitate the potential translational application of these cells.


Subject(s)
Dermis , Hair Follicle , Animals , Mice , Dermis/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Hair Follicle/physiology , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Skin
6.
Tissue Eng Part A ; 29(17-18): 491-505, 2023 09.
Article in English | MEDLINE | ID: mdl-37212289

ABSTRACT

The treatment of refractory cutaneous wounds remains to be a clinical challenge. There is growing evidence to show that mesenchymal stem cells (MSCs) have great potential in promoting wound healing. However, the therapeutic effects of MSCs are greatly dampened by their poor survival and engraftment in the wounds. To address this limitation, in this study, MSCs were grown into a collagen-glycosaminoglycan (C-GAG) matrix to form a dermis-like tissue sheet, named engineered dermal substitute (EDS). When seeded on C-GAG matrix, MSCs adhered rapidly, migrated into the pores, and proliferated readily. When applied onto excisional wounds in healthy and diabetic mice, the EDS survived well, and accelerated wound closure, compared with C-GAG matrix alone or MSCs in collagen hydrogel. Histological analysis revealed that EDS prolonged the retention of MSCs in the wounds, associated with increased macrophage infiltration and enhanced angiogenesis. RNA-Seq analysis of EDS-treated wounds uncovered the expression of abundant human chemokines and proangiogenic factors and their corresponding murine receptors, suggesting a mechanism of ligand/receptor-mediated signals in wound healing. Thus, our results indicate that EDS prolongs the survival and retention of MSCs in the wounds and enhances wound healing.


Subject(s)
Diabetes Mellitus, Experimental , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Mice , Humans , Animals , Diabetes Mellitus, Experimental/metabolism , Wound Healing , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cell Transplantation/methods
7.
Environ Sci Technol ; 57(14): 5714-5725, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36995247

ABSTRACT

Tire wear particles (TWPs) exposed to the aquatic environment are rapidly colonized by microorganisms and provide unique substrates for biofilm formation, which potentially serve as vectors for tetracycline (TC) to influence their behaviors and potential risks. To date, the photodegradation capacity of TWPs on contaminants due to biofilm formation has not been quantified. To accomplish this, we examined the ability of virgin TWPs (V-TWPs) and biofilm-developed TWPs (Bio-TWPs) to photodegrade TC when exposed to simulated sunlight irradiation. V-TWPs and Bio-TWPs accelerated the photodegradation of TC, with rates (kobs) of 0.0232 ± 0.0014 and 0.0152 ± 0.0010 h-1, respectively (kobs increased by 2.5-3.7 times compared to that for only TC solution). An important factor of increased TC photodegradation behavior was identified and linked to the changed reactive oxygen species (ROS) of different TWPs. The V-TWPs were exposed to light for 48 h, resulting in more ROS for attacking TC, with hydroxyl radicals (•OH) and superoxide anions (O2•-) playing a dominant role in TC photodegradation measured using scavenger/probe chemicals. This was primarily due to the greater photosensitization effects and higher electron-transfer capacity of V-TWPs in comparison to Bio-TWPs. In addition, this study first sheds light on the unique effect and intrinsic mechanism of the crucial role of Bio-TWPs in TC photodegradation, enhancing our holistic understanding of the environmental behavior of TWPs and the associated contaminants.


Subject(s)
Microplastics , Water Pollutants, Chemical , Photolysis , Plastics , Reactive Oxygen Species/chemistry , Anti-Bacterial Agents , Tetracycline , Water Pollutants, Chemical/analysis
8.
Stem Cell Res Ther ; 13(1): 507, 2022 10 22.
Article in English | MEDLINE | ID: mdl-36273220

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) have shown immense therapeutic potential for various brain diseases. Intrathecal administration of MSCs may enhance their recruitment to lesions in the central nervous system, but any impact on cerebrospinal fluid (CSF) flow remains unclear. METHODS: Rats with or without middle cerebral artery occlusion (MCAO) received intrathecal injections of 2D cultured MSCs, 3D cultured MSCs or an equal volume of artificial cerebrospinal fluid (ACSF). Ventricle volume was assessed by MRI on Days 2 and 14 post-MCAO surgery. A beam walking test was used to assess fine motor coordination and balance. Aggregation of MSCs was evaluated in CSF and frozen brain tissue. Differential expression of cell adhesion molecules was evaluated by RNA-Seq, flow cytometry and immunofluorescence analyses. The influence of VCAM-1 blockade in mediating the aggregation of 2D MSCs was investigated in vitro by counting cells that passed through a strainer and in vivo by evaluating ventricular dilation. RESULTS: MSC expanded in 2D culture formed aggregates in the CSF and caused ventricular enlargement in both MCAO and normal rats. Aggregates were associated with impaired motor function. 2D MSCs expressed higher levels of integrin α4 and VCAM-1 than 3D MSCs. Blockade of VCAM-1 in 2D MSCs reduced their aggregation in vitro and reduced lateral ventricular enlargement after intrathecal infusion. 3D MSCs exhibited lower cell aggregation and reduced cerebral ventricular dilation after intrathecal transplantation CONCLUSIONS: The aggregation of 2D MSCs, mediated by the interaction of integrin α4 and VCAM-1, is a potential risk for obstruction of CSF flow after intrathecal transplantation.


Subject(s)
Infarction, Middle Cerebral Artery , Integrin alpha4 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Vascular Cell Adhesion Molecule-1 , Animals , Rats , Infarction, Middle Cerebral Artery/genetics , Infarction, Middle Cerebral Artery/therapy , Integrin alpha4/genetics , Integrin alpha4/metabolism , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism
9.
Front Pediatr ; 10: 846560, 2022.
Article in English | MEDLINE | ID: mdl-35874593

ABSTRACT

Background: Maternal stress during pregnancy can raise the risk of mental disorders in offspring. The continuous emergence of clinical concepts and the introduction of new technologies are great challenges. In this study, through bibliometric analysis, the research trends and hotspots on prenatal stress (PS) were explored to comprehend clinical treatments and recommend future scientific research directions. Methods: Studies on PS published on the Web of Science Core Collection (WoSCC) database between 2011 and 2021 were reviewed. Bibliometric analysis was conducted according to the number of publications, keywords, journals, citations, affiliations, and countries. With the data collected from the WoSCC, visualization of geographic distribution; clustering analysis of keywords, affiliations, and authors; and descriptive analysis and review of PS were carried out. Results: A total of 7,087 articles published in 2011-2021 were retrieved. During this period, the number of publications increased. Psychoneuroendocrinology is the leading journal on PS. The largest contributor was the United States. The University of California system was leading among institutions conducting relevant research. Wang H, King S, and Tain YL were scholars with significant contributions. Hotspots were classified into four clusters, namely, pregnancy, prenatal stress, oxidative stress, and growth. Conclusion: The number of studies on PS increased. Journals, countries, institutions, researchers with the most contributions, and most cited articles worldwide were extracted. Studies have mostly concentrated on treating diseases, the application of new technologies, and the analysis of epidemiological characteristics. Multidisciplinary integration is becoming the focus of current development. Epigenetics is increasingly used in studies on PS. Thus, it constitutes a solid foundation for future clinical medical and scientific research.

10.
Behav Brain Res ; 432: 113973, 2022 08 26.
Article in English | MEDLINE | ID: mdl-35728732

ABSTRACT

Depression is a common mental disease that can lead to suicide when severe. Exposure to prenatal stress (PS) can lead to depression-like behavior in offspring, but the mechanism is unclear. RhoA (Ras homology family member A) plays an important role in stress-induced changes in synaptic plasticity, participating in the development of depression by activating the downstream effector ROCK (Rho-associated protein kinase). This study explored the influence in the expression of RhoA and downstream molecules ROCK1/2 in prenatally stressed rats, and the effect of RhoA inhibitor simvastatin on depression-like behavior induced by PS. Depression-like behavior in offspring was detected by sucrose preference test, forced swimming test, and open-field test. The mRNA and protein expression of RhoA and ROCK1/2 in the hippocampus and prefrontal cortex of offspring rats were detected by qRT-PCR and western blotting, respectively. Our results showed that PS causes depression-like behavior in offspring rats, associated with elevated expression of RhoA, ROCK1/2 in the hippocampus and prefrontal cortex. After administration of simvastatin to PS rats, the expression of RhoA and ROCK2 was significantly reduced, alleviating depression-like behavior. Our study demonstrated that RhoA participates in the depression-like behavior in prenatally stressed offspring rats, which may be a potential target for antidepressant therapy.


Subject(s)
Depression , Prenatal Exposure Delayed Effects , rho GTP-Binding Proteins/metabolism , Animals , Depression/drug therapy , Depression/etiology , Depression/metabolism , Female , Hippocampus/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Rats , Rats, Sprague-Dawley , Simvastatin/metabolism , Stress, Psychological/complications , Stress, Psychological/metabolism , rho-Associated Kinases/metabolism , rhoA GTP-Binding Protein/metabolism
11.
Front Med (Lausanne) ; 9: 868087, 2022.
Article in English | MEDLINE | ID: mdl-35602470

ABSTRACT

Objective: Artemisinin is an organic compound that comes from Artemisia annua. Artemisinin treatment is the most important and effective method for treating malaria. Bibliometric analysis was carried out to identify the global research trends, hot spots, scientific frontiers, and output characteristics of artemisinin from 2000 to 2021. Methods: Publications and their recorded information from 2000 to 2021 were retrieved through the Web of Science Core Collection (WoSCC). Using VOSviewer and Citespace, the hotspots and trends of studies on artemisinin were visualized. Results: A total of 8,466 publications were retrieved, and for the past 22 years, the annual number of publications associated with artemisinin kept increasing. The United States published most papers. The H-index and number of citations of the United States ranked first. The University of Oxford and MALARIA JOURNAL were the most productive affiliation and journal, respectively. A paper written by E.A. Ashley in 2011 achieved the highest global citation score. Keywords, such as "malaria," "artesunate," "plasmodium-falciparum," "in-vitro," "artemisinin resistance," "plasmodium falciparum," "resistance," and "artemether-lumefantrine," appeared most frequently. The research on artemisinin includes clinical research and animal and cell experiments. Conclusion: The biosynthesis, drug resistance mechanism, and combination of artemisinin have become more popular than before. Studies on artemisinin treating coronavirus disease 2019 (COVID-19) have been carried out, and good research results have been obtained.

12.
Front Pharmacol ; 13: 1088750, 2022.
Article in English | MEDLINE | ID: mdl-36744213

ABSTRACT

Background: Intrahepatic cholestasis (IC) is a disorder of bile production, secretion, and excretion with various causes. Crocin I (CR) is effective in the treatment of IC, but its underlying mechanisms need to be further explored. We aimed to reveal the therapeutic mechanism of crocin I for IC by combining an integrated strategy of metabolomics and transcriptomics. Methods: The hepatoprotective effect of CR against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) was evaluated in rats. The serum biochemical indices, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß), as well as the liver oxidative stress indexes and the pathological characteristics of the liver were analyzed. In addition, we also performed a serum metabolomics study using UPLC-Q Exactive HF-X technology to investigate the effect of CR on the serum of rats with ANIT-induced IC and screened potential biomarkers. The enrichment analysis of differential expressed genes (DEGs) was performed by transcriptomics. Finally, the regulatory targets of CR on potential biomarkers were obtained by combined analysis, and the relevant key targets were verified by western blotting. Results: CR improved serum and liver homogenate indexes and alleviated liver histological injury. Compared with ANIT group, the CR group had 76 differential metabolites, and 10 metabolic pathways were enriched. There were 473 DEGs significantly changed after CR treatment, most of which were enriched in the retinol metabolism, calcium signaling pathway, PPAR signaling pathway, circadian rhythm, chemokine signaling pathway, arachidonic acid metabolism, bile secretion, primary bile acid biosynthesis, and other pathways. By constructing the "compound-reaction-enzyme-gene" interaction network, three potential key-target regulation biomarkers were obtained, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), ATP-binding cassette transporter G5 (ABCG5), and sulfotransferase2A1(SULT2A1), which were further verified by western blotting. Compared with the ANIT group, the CR group significantly increased the expression of ABCG5 and SULT2A1, and the expression of HMGCR significantly decreased. Conclusion: Combined metabolomic and transcriptomic analyses show that CR has a therapeutic effect on IC through regulation of the biosynthesis of bile acids and bilirubin in the bile secretion pathway and regulation of the expression of HMGCR, ABCG5, and SULT2A1.

13.
Pharmacol Biochem Behav ; 210: 173269, 2021 11.
Article in English | MEDLINE | ID: mdl-34487773

ABSTRACT

Previous studies have shown that prenatal stress (PS) can potentially contribute to depression-like behavior in offspring and that this effect may be moderated by cross-fostering. However, the underlying mechanism of this effect remains to be determined. This study aimed to determine the effect of cross-fostering on the expression of EAAT2 and the SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats and to demonstrate functional effects on depression-like behavior. The impacts of cross-fostering were functionally assessed using the sucrose preference test (SPT), the forced swimming test (FST) and the elevated plus maze (EPM). Quantitative real-time PCR was used to determine changes in the expression of EAAT2 and SNAREs mRNA in the hippocampus and the prefrontal cortex of offspring rats. PS offspring rats showed significantly decreased sucrose preference and prolonged immobility time, while cross-fostering effectively increased sucrose preference and shorten the time of immobility. The expression of EAAT2 mRNA in PS offspring rats was markedly reduced, whilst the core mRNA expression of the SNARE complex increased. Our results provide strong evidence demonstrating that cross-fostering can alleviate depression-like behavior and regulate the abnormal expression levels of EAAT2 mRNA and SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats. Our findings contribute to further understanding of the pathogenesis of PS-induced depression and may help to inform the future development of novel treatment approaches.


Subject(s)
Depression/metabolism , Excitatory Amino Acid Transporter 2/metabolism , Prenatal Exposure Delayed Effects/metabolism , SNARE Proteins/metabolism , Stress, Psychological/metabolism , Animals , Behavior, Animal , Depression/psychology , Disease Models, Animal , Female , Hippocampus/metabolism , Prefrontal Cortex , Pregnancy , Prenatal Exposure Delayed Effects/psychology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley
14.
BMC Complement Med Ther ; 21(1): 222, 2021 Sep 03.
Article in English | MEDLINE | ID: mdl-34479552

ABSTRACT

BACKGROUND: Increasing attention has been paid to the effect of Epimedium on the nervous system, particularly anti-depression function. In the present study, we applied network pharmacology to introduce a testable hypothesis on the multi-target mechanisms of Epicedium against depression. METHODS: By reconstructing the network of protein-protein interaction and drug-component-target, we predicted the key protein targets of Epicedium for the treatment of depression. Then, through molecular docking, the interaction of the main active components of Epicedium and predicted candidate targets were verified. RESULTS: Nineteen active compounds were selected from Epicedium. There were 200 targets associated with Epicedium and 537 targets related to depression. The key targets of Epicedium for treating depression were IL6, VEGFA, AKT1, and EGF. According to gene ontology functional enrichment analysis, 22 items of biological process (BP), 13 items of cell composition (CC) and 9 items of molecular function (MF) were obtained. A total of 56 signaling pathways (P < 0.05) were identified by Kyoto Encyclopedia of Genes and Genomes analysis, mainly involving depression-related pathways such as dopaminergic synapse, TNF signaling pathway, and prolactin signaling pathway. The results of molecular docking showed that the most important activity components, including luteoklin, quercetin and kaempferol, were well combined with the key targets. CONCLUSIONS: Luteoklin, quercetin, kaempferol and other active compounds in Epicedium can regulate multiple signaling pathways and targets such as IL6, AKT1, and EGF, therefore playing therapeutic roles in depression.


Subject(s)
Depression/drug therapy , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional/methods , Molecular Docking Simulation/methods , Humans , Signal Transduction/drug effects
15.
Stem Cell Res Ther ; 12(1): 358, 2021 06 21.
Article in English | MEDLINE | ID: mdl-34154653

ABSTRACT

BACKGROUND: We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved. METHODS: Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq. RESULTS: We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke. CONCLUSIONS: Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.


Subject(s)
Brain Ischemia , Ischemic Stroke , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Stroke , Animals , Brain Ischemia/therapy , Cells, Cultured , Disease Models, Animal , Microglia , Rats , Stroke/therapy
16.
Stress ; 24(5): 612-620, 2021 09.
Article in English | MEDLINE | ID: mdl-34184955

ABSTRACT

Prenatal stress (PS) affects neurodevelopment and increases the risk for anxiety in adolescence in male offspring, but the mechanism is still unclear. N-Cadherin regulates the expression of AMPA receptors (AMPARs), which mediate anxiety by modulating network excitability in the prefrontal cortex (PFC). Our results revealed that in adolescent male, but not female, offspring rats, PS induced anxiety-like behavior, as assessed by the open field test (OFT). Furthermore, N-cadherin and AMPAR subunit GluA1 were colocalized in the PFC, and the expression of the N-cadherin and the GluA1 decreased following PS exposure in male offspring rats. We also found that the AMPAR agonist CX546 did not alleviate anxiety-like behavior in adolescent male offspring rats; however, it increased the expression of GluA1 in the PFC but did not alter the expression of N-cadherin. In conclusion, our study suggested that the N-cadherin-GluA1 pathway in the PFC mediates anxiety-like behavior in adolescent male offspring rats and that N-cadherin might be required for sex differences in the effect of PS on adolescent offspring.


Subject(s)
Cadherins , Prenatal Exposure Delayed Effects , Animals , Anxiety , Cadherins/genetics , Female , Male , Prefrontal Cortex , Pregnancy , Rats , Rats, Sprague-Dawley , Stress, Psychological
17.
Behav Brain Res ; 399: 113000, 2021 02 05.
Article in English | MEDLINE | ID: mdl-33161032

ABSTRACT

A large body of literature has demonstrated that prenatal stress (PS) can induce depression-like behavior in the offspring. However, the underlying mechanism remains largely unknown. CREB-regulated transcriptional coactivator 1(CRTC1) has recently been shown to involve in mood regulation. This research aims to investigate whether CRTC1 signaling was involved in the depression-like behavior of prenatally stressed offspring rats. Sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT) were adopted to test the depression-like behavior in the male offspring rats, and CRTC1 signaling was measured. The results showed that there were significantly reduced sucrose intake in SPT and prolonged immobility time in FST in PS-exposure offspring rats. It was also found decreased levels of total CRTC1, nuclear CRTC1, calcineurin, brain-derived neurotrophic factor (BDNF) and c-fos, but increased cytoplasmic p-CRTC1 in the hippocampus (HIP) and prefrontal cortex (PFC) of the offspring rats. Furthermore, the mRNA level of CRTC1, calcineurin, BDNF, c-fos were down-regulated. Abnormal expression of CRTC1 signaling could be alleviated by fluoxetine treatment. In conclusion, our research indicated that the aberration of CRTC1 expression and/or phosphorylation activity might play a vital role in PS-induced depression-like behavior of offspring rats.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Depression/metabolism , Prefrontal Cortex/metabolism , Prenatal Exposure Delayed Effects/metabolism , Signal Transduction/physiology , Stress, Psychological/metabolism , Transcription Factors/metabolism , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Brain-Derived Neurotrophic Factor/drug effects , Depression/drug therapy , Female , Fluoxetine/pharmacology , Male , Prefrontal Cortex/drug effects , Pregnancy , Prenatal Exposure Delayed Effects/drug therapy , Rats , Rats, Sprague-Dawley , Selective Serotonin Reuptake Inhibitors/pharmacology , Signal Transduction/drug effects , Transcription Factors/drug effects
18.
Zhongguo Zhong Yao Za Zhi ; 41(17): 3181-3185, 2016 Sep.
Article in Chinese | MEDLINE | ID: mdl-28920368

ABSTRACT

The application of ArcGIS and Maxent modelto analyze the ecological suitability of Gardenia jasminoides.Taking 85 batches of Gardenia as the basis of analysis, the selection of ecological factors for the growth of Gardenia. The results showed that the average precipitation in April, the average precipitation in November and the average precipitation in August were the most important factors affecting the growth of Gardenia. The relative concentration of Gardenia suitable growth region,north to the south of Shaanxi province, south of Henan, central Anhui, south to the north of Hainan province, west to central Sichuan province, east of Zhejiang coastal area, northeast of Taiwan.


Subject(s)
Gardenia/growth & development , China , Climate , Ecology , Geographic Information Systems
19.
Monoclon Antib Immunodiagn Immunother ; 34(5): 327-33, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26492620

ABSTRACT

Monoclonal antibodies are known to have several applications in clinical diagnosis and therapy. In the present study, the truncated S1 gene, encoding the exterior of the viral spike protein of porcine epidemic diarrhea virus (PEDV), was subcloned into prokaryotic expression vector pET32a (+) and expressed as a recombinant protein in Escherichia coli BL21(DE3). Female BALB/c mice were immunized with the purified recombinant truncated S1 protein, and three monoclonal antibodies (MAb designated as E3, G8, and G9) against the truncated S1 protein obtained by hydridoma technique. Further characterization demonstrated that the three MAbs (E2, G8, and G9) belong to IgG1 subclass and have different affinities (G9 > G8 > E3). Furthermore, all of the three MAbs reacted with PEDV in the fluorescent antibody assay. Our study suggests that purified truncated S1 protein and the three developed MAbs could be useful in the development of a diagnostic assay for anti-PEDV antibodies and PEDV antigen, respectively.


Subject(s)
Antibodies, Monoclonal/immunology , Porcine epidemic diarrhea virus/immunology , Recombinant Proteins/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Viral/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Escherichia coli/genetics , Female , Mice , Mice, Inbred BALB C , Swine , Swine Diseases/immunology , Swine Diseases/virology
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