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  • 1
    In: Aging, Impact Journals, LLC
    Type of Medium: Online Resource
    ISSN: 1945-4589
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2535337-8
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  • 2
    In: Brain Research, Elsevier BV, Vol. 1708 ( 2019-04), p. 58-68
    Type of Medium: Online Resource
    ISSN: 0006-8993
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1462674-3
    SSG: 12
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  • 3
    In: Cellular Physiology and Biochemistry, S. Karger AG, Vol. 46, No. 5 ( 2018), p. 2173-2186
    Abstract: Background/Aims: Both experimental and clinical studies have revealed satisfactory effects of the traditional Chinese formula Buyang Huanwu decoction (BYHWD) in improving post-intracerebral hemorrhage (ICH) neurological deficiencies. However, the multifaceted mechanisms of BYHWD in ICH treatment are not comprehensively understood. The present study explored various therapeutic targets of BYHWD by using lncRNA and mRNA transcriptomics. Methods: LncRNA and mRNA microarrays were used to identify differentially expressed genes. ICH-induced upregulated genes (ICH vs sham) and BYHWD-induced downregulated genes (BYHWD vs ICH) were first identified. The intersection between these 2 sets was determined to identify ICH-induced highly expressed genes that were reversed by BYHWD. Then, the genes downregulated after ICH and the genes upregulated after BYHWD treatment were used to generate another set of intersections. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were subsequently performed to determine relative biological functions and signaling transduction pathways according to genes within the intersections. Quantitative real-time PCR was used to validate changes in gene expression observed using the microarray. Finally, a lncRNA-mRNA co-expression network was established to identify links among the genes within the intersections. Results: A total of 18 differentially expressed lncRNAs and 33 differentially expressed mRNAs were identified using 2 lncRNA arrays (ICH vs sham and BYHWD vs ICH). The altered genes were enriched in the hemoglobin complex, oxygen transport and oxygen transporter and were closely associated with pyruvate metabolism. The co-expression network consisted of 53 nodes and 595 connections (308 positive interactions and 287 negative interactions). Conclusion: The hemoglobin complex, oxygen transport, oxygen transporter activity and pyruvate metabolism are possible therapeutic targets of BYHWD in ICH treatment. The present study provides the basis and direction for future investigations to explore the mechanisms by which BYHWD protects against long-term neurological deficiencies after ICH.
    Type of Medium: Online Resource
    ISSN: 1015-8987 , 1421-9778
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1482056-0
    SSG: 12
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Hindawi Limited ; 2020
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2020 ( 2020-06-29), p. 1-12
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2020 ( 2020-06-29), p. 1-12
    Abstract: As a bioactive absorbed compound of rhubarb, Rhein is applied for the treatment of brain injury. However, the underlying pharmacological mechanisms remain unclear. In this study, we aimed to explore antineuroinflammatory functions and underlying mechanisms of Rhein in vitro. BV2 microglia cells were chosen and irritated by LPS. The influence of Rhein on cell viability was determined using MTT assay. We finely gauged the proinflammatory cytokines of TNF- α and IL-1 β through tests of immunofluorescence staining, ELISA, RT-qPCR, and western blot. Additionally, mediators including IL-6, IL-12, iNOS, and IL-10 were surveyed by ELISA. Furthermore, protein levels of the underlying signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF- κ B) were tested adopting western blot. We found that Rhein reduced the secretion of pivotal indicators including TNF- α and IL-1 β , effectively restraining their mRNA and protein expression in LPS-activated BV2 microglial cells. Besides, Rhein treatment demoted the production of IL-6, IL-12, and iNOS and promoted the excretion of IL-10. Subsequent mechanistic experiments revealed that Rhein obviously downregulated the phosphorylation levels of PI3K, Akt, p38, and ERK1/2 and simultaneously upregulated the PTEN expression. In addition, Rhein antagonized the increase of TLR4, p-I κ B α , and NF- κ B. In summary, Rhein suppresses neuroinflammation via multiple signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF- κ B) in LPS-stimulated BV2 microglia cells. This study highlights a natural agent for prevention and treatment of neuroinflammation.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2148302-4
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  • 5
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 134, No. 5 ( 2021-05), p. 1515-1526
    Abstract: Thrombin is a unique factor that triggers post-intracerebral hemorrhage (ICH) angiogenesis by increasing hypoxia-inducible factor–1α (HIF-1α) at the protein level. However, HIF-1α mRNA remains unchanged. MicroRNAs (miRNAs) mediate posttranscriptional regulation by suppressing protein translation from mRNAs. This study aimed to determine if miRNAs might be involved in thrombin-induced angiogenesis after ICH by targeting HIF-1α or its upstream prolyl hydroxylase domains (PHDs). METHODS The study was divided into two parts. In part 1, rats received an injection of thrombin into the right globus pallidus. An miRNA array combined with miRNA target prediction, luciferase activity assay, and miRNA mimic/inhibitor transfection were used to identify candidate miRNAs and target genes. Part 2 included experiments 1 and 2. In experiment 1, rats were randomly divided into the sham group, ICH group, and ICH+hirudin–treated (thrombin inhibitor) group. In experiment 2, the rats were randomly divided into the sham group, ICH group, ICH+antagomir group, ICH+antagomir-control group, and ICH+vehicle group. Western blotting and quantitative real-time polymerase chain reaction were used to determine the expression of protein and miRNA, respectively. The coexpression of miR-24–1-5p (abbreviated to miR-24) and von Willebrand factor was detected by in situ hybridization and immunohistochemical analysis. The angiogenesis was evaluated by double-labeling immunofluorescence. Neurological function was evaluated by body weight, modified Neurological Severity Scores, and corner turn and foot-fault tests. RESULTS In part 1, it was shown that miR-24, which is predicted to target PHD1, was upregulated (fold-change of 1.83) after thrombin infusion, and that the miR-24 mimic transfection decreased luciferase activity and downregulated PHD1 expression (p 〈 0.05). miR-24 inhibitor transfection increased PHD1 expression (p 〈 0.05). In part 2, it was shown that miR-24 was expressed in endothelial cells. The HIF-1α protein level and proliferating cell nuclear antigen–positive (PCNA + ) nuclei in vessels were increased, while the PHD1 protein level was decreased after ICH, and these effects were reversed by hirudin (p 〈 0.05). The antagomiR-24–treated rats exhibited a markedly lower body weight and significantly poorer recovery from neurological deficit compared with those in ICH groups (p 〈 0.05). AntagomiR-24 intervention also led to lower miR-24 expression, a higher PHD1 protein level, and fewer PCNA + nuclei in vessels compared with those in ICH groups (p 〈 0.05). CONCLUSIONS The present study suggests that thrombin reduces HIF-1α degradation and initiates angiogenesis by increasing miR-24, which targets PHD1 after ICH.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    RVK:
    RVK:
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2021
    detail.hit.zdb_id: 2026156-1
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Psychiatry Vol. 13 ( 2022-8-18)
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 13 ( 2022-8-18)
    Abstract: Although various susceptibility genes have been revealed to influence tobacco smoking, the underlying regulatory mechanisms between genetic variants and smoking are poorly understood. In this study, we investigated cis -expression quantitative trait loci ( cis -eQTLs) and methylation quantitative trait loci (mQTLs) for 56 candidate smoking-linked genes using the BrainCloud cohort samples. An eQTL was revealed to significantly affect EGLN2 expression in the European sample and two mQTLs were respectively detected in CpG sites in NRXN1 and CYP2A7 . Interestingly, we found for the first time that the minor allele of the single nucleotide polymorphism (SNP) rs3745277 located in CYP2A7P1 (downstream of CYP2B6 ) significantly decreased methylation at the CpG site for CYP2A7 (cg25427638; P = 5.31 × 10 –7 ), reduced expression of CYP2B6 ( P = 0.03), and lowered the percentage of smokers (8.8% vs. 42.3%; Odds Ratio (OR) = 0.14, 95% Confidence Interval (CI): 0.02–0.62; P = 4.47 × 10 –3 ) in a dominant way for the same cohort sample. Taken together, our findings resulted from analyzing genetic variation, DNA methylation, mRNA expression, and smoking status together using the same participants revealed a regulatory mechanism linking mQTLs to the smoking phenotype. Moreover, we demonstrated the presence of different regulatory effects of low-frequency and common variants on mRNA expression and DNA methylation.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564218-2
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-5-7)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-5-7)
    Abstract: Intracerebral hemorrhage (ICH) is a life-threatening type of stroke that lacks effective treatments. The inflammatory response following ICH is a vital response that affects brain repair and organism recovery. The nuclear factor κB (NF-κB) signaling pathway is considered one of the most important inflammatory response pathways and one of its response pathways, the noncanonical NF-κB signaling pathway, is known to be associated with persistent effect and chronic inflammation. NF-κB–inducing kinase (NIK) via the noncanonical NF-κB signaling plays a key role in controlling inflammation. Here, we investigated potential effects of the traditional Chinese medicine formula Buyang Huanwu Decoction (BYHWD) on inflammatory response in a rat model of ICH recovery by inhibiting the NIK-mediated the noncanonical NF-κB signaling pathway. In the first part, rats were randomly divided into three groups: the sham group, the ICH group, and the BYHWD group. ICH was induced in rats by injecting collagenase (type VII) into the right globus pallidus of rats' brain. For the BYHWD group, rats were administered BYHWD (4.36 g/kg) once a day by intragastric administration until they were sacrificed. Neurological function was evaluated in rats by a modified neurological severity score (mNSS), the corner turn test, and the foot-fault test. The cerebral edema showed the degree of inflammatory response by sacrificed brain water content. Western blot and real-time quantitative reverse transcription PCR tested the activity of inflammatory response and noncanonical NF-κB signaling. In the second part, siRNA treatment and assessment of inflammation level as well as alterations in the noncanonical NF-κB signaling were performed to determine whether the effect of BYHWD on inflammatory response was mediated by suppression of NIK via the noncanonical NF-κB signaling pathway. We show that BYHWD treated rats exhibited: (i) better health conditions and better neural functional recovery; (ii) decreased inflammatory cytokine and the edema; (iii) reduced expression of NIK, a key protein in unregulated the noncanonical NF-κB signaling pathways; (iv) when compared with pretreated rats with NIK targeting (NIK siRNAs), showed the same effect of inhibiting the pathway and decreased inflammatory cytokine. BYHWD can attenuate the inflammatory response during ICH recovery in rats by inhibiting the NIK-mediated noncanonical NF-κB signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 8
    In: International Journal of Biological Sciences, Ivyspring International Publisher, Vol. 15, No. 4 ( 2019), p. 895-908
    Type of Medium: Online Resource
    ISSN: 1449-2288
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2019
    detail.hit.zdb_id: 2179208-2
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2018
    In:  Experimental & Molecular Medicine Vol. 50, No. 7 ( 2018-7), p. 1-12
    In: Experimental & Molecular Medicine, Springer Science and Business Media LLC, Vol. 50, No. 7 ( 2018-7), p. 1-12
    Type of Medium: Online Resource
    ISSN: 1226-3613 , 2092-6413
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2084833-X
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  • 10
    In: Chinese Medicine, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2023-11-13)
    Abstract: In this study, we aimed to combine transcriptomic and network pharmacology to explore the crucial mRNAs and specific regulatory molecules of Buyang Huanwu Decoction (BYHWD) in intracerebral hemorrhage (ICH) treatment. Methods C57BL/6 mice were randomly divided into three groups: sham, ICH, and BYHWD. BYHWD (43.29 g/kg) was administered once a day for 7 days. An equal volume of double-distilled water was used as a control. Behavioural and histopathological experiments were conducted to confirm the neuroprotective effects of BYHWD. Brain tissues were collected for transcriptomic detection. Bioinformatics analysis were performed to illustrate the target gene functions. Network pharmacology was used to predict potential targets for BYHWD. Next, transcriptomic assays were combined with network pharmacology to identify the potential differentially expressed mRNAs. Immunofluorescence staining, real-time polymerase chain reaction, western blotting, and transmission electron microscopy were performed to elucidate the underlying mechanisms. Results BYHWD intervention in ICH reduced neurological deficits. Network pharmacology analysis identified 203 potential therapeutic targets for ICH, whereas transcriptomic assay revealed 109 differentially expressed mRNAs post-ICH. Among these, cathepsin B, ATP binding cassette subfamily B member 1, toll-like receptor 4, chemokine (C–C motif) ligand 12, and baculoviral IAP repeat-containing 5 were identified as potential target mRNAs through the integration of transcriptomics and network pharmacology approaches. Bioinformatics analysis suggested that the beneficial effects of BYHWD in ICH may be associated with apoptosis, animal autophagy signal pathways, and PI3K-Akt and mTOR biological processes. Furthermore, BYHWD intervention decreased Ctsb expression levels and increased autophagy levels in ICH. Conclusions Animal experiments in combination with bioinformatics analysis confirmed that BYHWD plays a neuroprotective role in ICH by regulating Ctsb to enhance autophagy.
    Type of Medium: Online Resource
    ISSN: 1749-8546
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2260322-0
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