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1.
Front Microbiol ; 14: 1304874, 2023.
Article in English | MEDLINE | ID: mdl-38116529

ABSTRACT

Myxococcus xanthus and Escherichia coli represent a well-studied microbial predator-prey pair frequently examined in laboratory settings. While significant progress has been made in comprehending the mechanisms governing M. xanthus predation, various aspects of the response and defensive mechanisms of E. coli as prey remain elusive. In this study, the E. coli MG1655 large-scale chromosome deletion library was screened, and a mutant designated as ME5012 was identified to possess significantly reduced susceptibility to predation by M. xanthus. Within the deleted region of ME5012 encompassing seven genes, the significance of dusB and fis genes in driving the observed phenotype became apparent. Specifically, the deletion of fis resulted in a notable reduction in flagellum production in E. coli, contributing to a certain level of resistance against predation by M. xanthus. Meanwhile, the removal of dusB in E. coli led to diminished inducibility of myxovirescin A production by M. xanthus, accompanied by a slight decrease in susceptibility to myxovirescin A. These findings shed light on the molecular mechanisms underlying the complex interaction between M. xanthus and E. coli in a predatory context.

2.
J Agric Food Chem ; 71(40): 14483-14492, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37751549

ABSTRACT

Plant pathogenic fungi and viruses are seriously threatening agricultural production. There is an urgent need to develop novel fungicides and antiviral agents with low toxicity and high efficiency. In this study, we designed and synthesized 32 thiazole-, hydrazone-, and amide-containing derivatives of laurene and systematically evaluated their antiviral activities and fungicidal activities. Structure-simplified compounds 5a-5c, 5i, 5k, 5l, 11a, 11j, and 12c displayed higher antiviral activities than that of ningnanmycin. Compound 11a with a simple chemical structure, convenient synthetic route, and excellent antiviral activity emerged as a secondary lead compound. The docking results show that compounds 5i, 5k, and 11a have strong interactions with the tobacco mosaic virus coat protein (TMV CP). These compounds also exhibited significant fungicidal activities. Compounds 5g, 5k, 11j, and 11l displayed 9.15-17.45 µg/mL EC50 values against Pyricularia grisea, and compounds 5h (EC50: 8.01 µg/mL) and 11i (EC50: 15.23 µg/mL) exhibited a similar level of EC50 values with chlorothalonil (EC50: 7.33 µg/mL) against Physalospora piricola. Preliminary fungicidal mechanism research indicated that compound 5h has a certain destructive effect on the hyphae of P. piricola. This work lays a foundation for the application of laurene derivatives in plant protection.

3.
Hortic Res ; 10(9): uhad148, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37691966

ABSTRACT

Jujube witches' broom (JWB) phytoplasmas parasitize the sieve tubes of diseased phloem and cause an excessive proliferation of axillary shoots from dormant lateral buds to favour their transmission. In previous research, two JWB effectors, SJP1 and SJP2, were identified to induce lateral bud outgrowth by disrupting ZjBRC1-mediated auxin flux. However, the pathogenesis of JWB disease remains largely unknown. Here, tissue-specific transcriptional reprogramming was examined to gain insight into the genetic mechanisms acting inside jujube lateral buds under JWB phytoplasma infection. JWB phytoplasmas modulated a series of plant signalling networks involved in lateral bud development and defence, including auxin, abscisic acid (ABA), ethylene, jasmonic acid, and salicylic acid. JWB-induced bud outgrowth was accompanied by downregulation of ABA synthesis within lateral buds. ABA application rescued the bushy appearances of transgenic Arabidopsis overexpressing SJP1 and SJP2 in Col-0 and ZjBRC1 in the brc1-2 mutant. Furthermore, the expression of ZjBRC1 and ABA-related genes ZjHB40 and ZjNCED3 was negatively correlated with lateral main bud outgrowth in decapitated healthy jujube. Molecular evidence showed that ZjBRC1 interacted with ZjBRC2 via its N-terminus to activate ZjHB40 and ZjNCED3 expression and ABA accumulation in transgenic jujube calli. In addition, ZjBRC1 widely regulated differentially expressed genes related to ABA homeostasis and ABA signalling, especially by binding to and suppressing ABA receptors. Therefore, these results suggest that JWB phytoplasmas hijack the ZjBRC1-mediated ABA pathways to stimulate lateral bud outgrowth and expansion, providing a strategy to engineer plants resistant to JWB phytoplasma disease and regulate woody plant architecture to promote crop yield and quality.

4.
bioRxiv ; 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37425680

ABSTRACT

Liquid biopsy analysis of cell-free DNA (cfDNA) has revolutionized cancer research by enabling non-invasive assessment of tumor-derived genetic and epigenetic changes. In this study, we conducted a comprehensive paired-sample differential methylation analysis (psDMR) on reprocessed methylation data from two large datasets, CPTAC and TCGA, to identify and validate differentially methylated regions (DMRs) as potential cfDNA biomarkers for head and neck squamous cell carcinoma (HNSC). Our hypothesis is that the paired sample test provides a more suitable and powerful approach for the analysis of heterogeneous cancers like HNSC. The psDMR analysis revealed a significant number of overlapped hypermethylated DMRs between two datasets, indicating the reliability and relevance of these regions for cfDNA methylation biomarker discovery. We identified several candidate genes, including CALCA, ALX4, and HOXD9, which have been previously established as liquid biopsy methylation biomarkers in various cancer types. Furthermore, we demonstrated the efficacy of targeted region analysis using cfDNA methylation data from oral cavity squamous cell carcinoma and nasopharyngeal carcinoma patients, further validating the utility of psDMR analysis in prioritizing cfDNA methylation biomarkers. Overall, our study contributes to the development of cfDNA-based approaches for early cancer detection and monitoring, expanding our understanding of the epigenetic landscape of HNSC, and providing valuable insights for liquid biopsy biomarker discovery not only in HNSC and other cancer types.

5.
NAR Genom Bioinform ; 5(2): lqad055, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37332657

ABSTRACT

Identifying novel and reliable prognostic biomarkers for predicting patient survival outcomes is essential for deciding personalized treatment strategies for diseases such as cancer. Numerous feature selection techniques have been proposed to address the high-dimensional problem in constructing prediction models. Not only does feature selection lower the data dimension, but it also improves the prediction accuracy of the resulted models by mitigating overfitting. The performances of these feature selection methods when applied to survival models, on the other hand, deserve further investigation. In this paper, we construct and compare a series of prediction-oriented biomarker selection frameworks by leveraging recent machine learning algorithms, including random survival forests, extreme gradient boosting, light gradient boosting and deep learning-based survival models. Additionally, we adapt the recently proposed prediction-oriented marker selection (PROMISE) to a survival model (PROMISE-Cox) as a benchmark approach. Our simulation studies indicate that boosting-based approaches tend to provide superior accuracy with better true positive rate and false positive rate in more complicated scenarios. For demonstration purpose, we applied the proposed biomarker selection strategies to identify prognostic biomarkers in different modalities of head and neck cancer data.

6.
iScience ; 26(2): 105915, 2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36685033

ABSTRACT

Cancer prognosis prediction is critical to the clinical decision-making process. Currently, the high availability of transcriptome datasets allows us to extract the gene modules with promising prognostic values. However, the biomarker identification is greatly challenged by tumor and patient heterogeneity. In this study, a framework of three subnetwork-based strategies is presented, incorporating hypothesis-driven, data-driven, and literature-based methods with informative visualization to prioritize candidate genes. By applying the proposed approaches to a head and neck squamous cell cancer (HNSCC) transcriptome dataset, we successfully identified multiple HNSCC-specific gene modules with improved prognostic values and mechanism information compared with the standard gene panel selection methods. The proposed framework is general and can be applied to any type of omics data. Overall, the study demonstrates and supports the use of the subnetwork-based approach for distilling reliable and biologically meaningful prognostic factors.

7.
Mol Carcinog ; 62(4): 493-502, 2023 04.
Article in English | MEDLINE | ID: mdl-36636912

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous disease that involves multiple anatomic sites, is a leading cause of cancer-related mortality worldwide. Although the utility of noninvasive biomarkers based on circulating cell-free DNA (cfDNA) methylation profiling has been widely recognized, limited studies have been reported so far regarding the dynamics of cfDNA methylome in oral cavity squamous cell carcinoma (OCSCC). It is hypothesized in this study that comparison of methylation profiles in pre- and postsurgery plasma samples will reveal OCSCC-specific prognostic and diagnostic biomarkers. As a strategy to further prioritize tumor-specific targets, top differential methylated regions (DMRs) were called by reanalyzing methylation data from paired tumor and normal tissue collected in the the cancer genome atlas head-neck squamous cell carcinoma (TCGA) head and neck cancer cohort. Matched plasma samples from eight patients with OCSCC were collected at Moffitt Cancer Center before and after surgical resection. Plasma-derived cfDNA was analyzed by cfMBD-seq, which is a high-sensitive methylation profiling assay. Differential methylation analysis was then performed based on the matched samples profiled. In the top 200 HNSCC-specific DMRs detected based on the TCGA data set, a total of 23 regions reached significance in the plasma-based DMR test. The top five validated DMR regions (ranked by the significance in the plasma study) are located in the promoter regions of genes PENK, NXPH1, ZIK1, TBXT, and CDO1, respectively. The genome-wide cfDNA DMR analysis further highlighted candidate biomarkers located in genes SFRP4, SOX1, IRF4, and PCDH17. The prognostic relevance of candidate genes was confirmed by survival analysis using the TCGA data. This study supports the utility of cfDNA-based methylome profiling as a promising noninvasive biomarker source for OCSCC and HNSCC.


Subject(s)
Carcinoma, Squamous Cell , Cell-Free Nucleic Acids , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/surgery , Epigenome , DNA Methylation , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/surgery , Mouth Neoplasms/genetics , Mouth Neoplasms/surgery , Cell-Free Nucleic Acids/genetics
8.
Front Psychol ; 13: 815147, 2022.
Article in English | MEDLINE | ID: mdl-35664195

ABSTRACT

In the Chinese society, where power distance is high, leaders' attitudes and behavior toward employees determine their career development as well as affect the entire team's performance. Therefore, exploring the kind of employees that leaders expect in China is essential. Based on implicit followership theory perspective, this study considers leaders' positive implicit followership (LPIF) as the main research variable and examines its influence on employees' innovative behavior (EIB). Moreover, it explores the multiple mediation effect of the leader-member exchange (LMX) relationship and psychological empowerment (PE) in this influence mechanism. The study sample comprised 389 leaders and their direct employees at 45 large- and medium-sized enterprises in Shandong, Beijing, Hebei, Shanghai, Shanxi, Zhejiang, and other regions of China. We used the leader-employee 1:1 matching questionnaire, and the longitudinal research design was adopted to avoid homology variance, making the study results more realistic and reliable. This study used the SPSS 26.0 and AMOS 26.0 statistical software to verify the hypotheses. Our findings show that LPIF has a significant positive effect on EIB, and LMX and PE have multiple mediation effects on the relationship between LPIF and EIB. When the level of LPIF is high, LMX and PE are also enhanced, which in turn promotes the increase in EIB. This study provides a new perspective for subsequent research on the psychological mechanism of employees and suggests an important method for understanding leadership and following processes in an organization. It plays a guiding role for the management practice of an enterprise, selection of leaders, and training of employees.

9.
Front Microbiol ; 13: 861865, 2022.
Article in English | MEDLINE | ID: mdl-35531272

ABSTRACT

Extracellular DNA (eDNA) is a critical component in the extracellular matrix (ECM) of bacterial biofilms, while little is known about the mechanisms underlying how eDNA integrates into the ECM through potential macromolecular interactions. Myxococcus xanthus biofilm was employed as a suitable model for the investigation due to the co-distribution of eDNA and exopolysaccharides (EPS) owing to their direct interactions in the ECM. DNA is able to combine with M. xanthus EPS to form a macromolecular conjugate, which is dominated by the electrostatic forces participating in the polymer-polymer interactions. Without intercalation binding, DNA-EPS interactions exhibit a certain degree of reversibility. Acting as a strong extracellular framework during biofilm formation process, the eDNA-EPS complex not only facilitates the initial cell adhesion and subsequent establishment of ECM architecture, but also renders cells within biofilms stress resistances that are relevant to the survival of M. xanthus in some hostile environments. Furthermore, the EPS protects the conjugated DNA from the degradation by nucleic acid hydrolases, which leads to the continuous and stable existence of eDNA in the native ECM of M. xanthus biofilms. These results will shed light on developing prevention and treatment strategies against biofilm-related risks.

10.
Front Psychol ; 11: 1853, 2020.
Article in English | MEDLINE | ID: mdl-32903662

ABSTRACT

How to make use of leaders' psychological capital to improve the innovation behavior of employees has become an important issue for the talent management of enterprises today, and it is also the goal that enterprises must pursue if they want to stand out in fierce competition. Therefore, a total of 154 enterprises in a high-tech area were selected for questionnaire survey in this study. The correlation between leader-member exchange (LMX) relationship (emotion, loyalty, contribution, and professional respect), leaders' psychological capital (confidence, hope, optimism, and tenacity), and employees' innovation behaviors were analyzed based on multivariate regression. Hierarchical regression method was used to examine the mediating effect of the LMX. It was found that confidence, toughness, and contribution were significantly positively correlated with employee innovation behavior (p < 0.001). The positive correlation between hope, optimism, emotion, and loyalty with employees' innovation behavior was significant (p < 0.05). Besides, emotion, loyalty, and contribution had mediating effects on the leaders' psychological capital and the innovation behavior of employees. In conclusion, leaders' psychological capital can have a significant positive effect on the innovation behavior of employees directly, and it can also have an indirect positive effect on the innovation behavior of employees by maintaining high quality LMX.

11.
Elife ; 92020 08 05.
Article in English | MEDLINE | ID: mdl-32755541

ABSTRACT

Telomeres define the natural ends of eukaryotic chromosomes and are crucial for chromosomal stability. The budding yeast Cdc13, Stn1 and Ten1 proteins form a heterotrimeric complex, and the inactivation of any of its subunits leads to a uniformly lethal phenotype due to telomere deprotection. Although Cdc13, Stn1 and Ten1 seem to belong to an epistasis group, it remains unclear whether they function differently in telomere protection. Here, we employed the single-linear-chromosome yeast SY14, and surprisingly found that the deletion of CDC13 leads to telomere erosion and intrachromosome end-to-end fusion, which depends on Rad52 but not Yku. Interestingly, the emergence frequency of survivors in the SY14 cdc13Δ mutant was ~29 fold higher than that in either the stn1Δ or ten1Δ mutant, demonstrating a predominant role of Cdc13 in inhibiting telomere fusion. Chromosomal fusion readily occurred in the telomerase-null SY14 strain, further verifying the default role of intact telomeres in inhibiting chromosome fusion.


Subject(s)
Cell Cycle Proteins/genetics , Chromosomal Proteins, Non-Histone/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Telomere-Binding Proteins/genetics , Telomere/physiology , Cell Cycle Proteins/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Telomere-Binding Proteins/metabolism
12.
Cell Mol Bioeng ; 12(5): 375-388, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31719921

ABSTRACT

INTRODUCTION: Treatment options for cancer metastases, the primary cause of cancer mortality, are limited. The chemokine receptor CXCR4 is an attractive therapeutic target in cancer because it mediates metastasis by inducing cancer cell and macrophage migration. Here we engineered carrier-free CXCR4-targeting RNA-protein nanoplexes that not only inhibited cellular migration but also polarized macrophages to the M1 phenotype. MATERIALS AND METHODS: A CXCR4-targeting single-chain variable fragment (scFv) antibody was fused to a 3030 Da RNA-binding protamine peptide (RSQSRSRYYRQRQRSRRRRRRS). Self-assembling nanoplexes were formed by mixing the CXCR4-scFv-protamine fusion protein (CXCR4-scFv-RBM) with miR-127-5p, a miRNA shown to mediate M1 macrophage polarization. RNA-protein nanoplexes were characterized with regard to their physicochemical properties and therapeutic efficacy. RESULTS: CXCR4-targeting RNA-protein nanoplexes simultaneously acted as a targeting ligand, a macrophage polarizing drug, and a miRNA delivery vehicle. Our carrier-free, RNA-protein nanoplexes specifically bound to CXCR4-positive macrophages and breast cancer cells, showed high drug loading (~ 90% w/w), and are non-toxic. Further, these RNA-protein nanoplexes significantly inhibited cancer and immune cell migration (75 to 99%), robustly polarized macrophages to the tumor-suppressive M1 phenotype, and inhibited tumor growth in a mouse model of triple-negative breast cancer. CONCLUSIONS: We engineered a novel class of non-toxic RNA-protein nanoplexes that modulate the tumor stroma. These nanoplexes are promising candidates for add-ons to clinically approved chemotherapeutics.

13.
Article in English | MEDLINE | ID: mdl-31461936

ABSTRACT

From the perspective of green growth, which seeks to coordinate and make sustainable the development of resources, the environment, and the economy, this study's aim was to find out whether the high-tech industry along the Belt and Road (B&R) is sustainable and effective in using resources, reducing environmental pollution, and increasing performance. This study used panel data covering 16 provinces (municipalities) along the B&R in China between 2009 and 2016. This study used the directional distance function (DDF) and the global Malmquist-Luenberger (GML) index model to analyze the technological innovation efficiency (TIE) of the high-tech industry (HTI) while considering the undesirable output (environmental pollution). Further, supplemented by ArcGIS geographical analysis, this study carried out a comparative analysis of the TIE and its decomposition in the HTI along the B&R from geographical and time-series dimensions. Moreover, the panel Tobit regression model was used to analyze the influencing factors of TIE. The results show that the direct financial support of the government has no impact on the improvement of TIE in the HTI, the government's regulation of environmental pollution can significantly affect the improvement of the TIE, the intensity of R&D has a significantly negative impact on the TIE, a higher level of R&D personnel in the HTI can be helpful in improving TIE, and increasing the import and export trade volumes of the HTI can promote TIE.


Subject(s)
Conservation of Natural Resources/methods , Efficiency, Organizational , Industry/organization & administration , Sustainable Development , China
14.
Biomed Pharmacother ; 109: 2262-2269, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30551483

ABSTRACT

The functions of 4-acetylantroquinonol B (4-AAQB), a ubiquinone derivative isolated from the mycelium of Antrodia cinnamomea, in immunotherapy for liver cancer were investigated. We found that 4-AAQB could inhibit liver cancer stem cell related manifestations and activate the antitumor ability of dendritic cells. Specifically, 4-AAQB can inhibit EpCAM, AFP and related pathways of HepG2 cells. It also significantly decreases the expression of ß-catenin, inhibits the tumorigenicity and decreases the secretion of immune escape related cytokines. Moreover, 4-AAQB can stimulate the proliferation of immune cells and promote the endocytosis of immature dendritic cells. When co-cultured immature dendritic cells with EpCAM+ HepG2 cells, 4-AAQB enhanced the expression of MHC class I and II on the surface of liver cancer stem cells and dendritic cells, increased the expression of costimulatory molecules CD80 of dendritic cells and cytokines related to immune activation. In conclusion, 4-AAQB from Antrodia cinnamomea can enhance immune function of dendritic cells against liver cancer stem cells, and may have the potential to be used for liver cancer prevention and immunotherapy.


Subject(s)
4-Butyrolactone/analogs & derivatives , Antrodia , Cyclohexanones/pharmacology , Dendritic Cells/immunology , Immunity, Cellular/immunology , Liver Neoplasms/immunology , Neoplastic Stem Cells/immunology , 4-Butyrolactone/isolation & purification , 4-Butyrolactone/pharmacology , 4-Butyrolactone/therapeutic use , Animals , Cell Survival/drug effects , Cell Survival/immunology , Coculture Techniques , Cyclohexanones/isolation & purification , Cyclohexanones/therapeutic use , Dendritic Cells/drug effects , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , Immunity, Cellular/drug effects , Liver Neoplasms/drug therapy , Mice , Neoplastic Stem Cells/drug effects , RAW 264.7 Cells
16.
Sci Rep ; 7(1): 3958, 2017 06 21.
Article in English | MEDLINE | ID: mdl-28638103

ABSTRACT

Early detection of neck lymph node (LN) recurrence is paramount in improving the prognosis of treated head and neck cancer patients. Ultrasound (US) with US-guided fine needle aspiration (FNA) and core needle biopsy (CNB) have been shown to have great accuracy for LN diagnoses in the untreated neck. However, in the treated neck with fibrosis, their roles are not clarified. Here, we retrospectively review 153 treated head and neck cancer patients who had received US and US-guided FNA/CNB. In multivariate logistic regression analyses, size (short-axis diameter >0.8 cm) (odds ratio (OR) 4.19, P = 0.007), round shape (short/long axis ratio >0.5) (OR 3.44, P = 0.03), heterogeneous internal echo (OR 3.92, P = 0.009) and irregular margin (OR 7.32, P < 0.001) are effective US features in predicting recurrent LNs in the treated neck. However, hypoechogenicity (OR 2.38, P = 0.289) and chaotic/absent vascular pattern (OR 3.04, P = 0.33) are ineffective. US-guided FNA (sensitivity/specificity: 95.24%/97.92%) is effective in the treated neck, though with high non-diagnostic rate (29.69%). US-guided CNB (sensitivity/specificity: 84.62%/100%) is also effective, though with low negative predictive value (62.5%). Overall, US with US-guided FNA/CNB are still effective diagnostic tools for neck nodal recurrence surveillance.


Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Lymph Nodes/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Adult , Aged , Biopsy, Fine-Needle/methods , Biopsy, Large-Core Needle/methods , Female , Head and Neck Neoplasms/pathology , Humans , Image-Guided Biopsy/methods , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Sensitivity and Specificity , Ultrasonography , Young Adult
17.
Biomed Pharmacother ; 93: 208-217, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28641163

ABSTRACT

6-shogaol is a phytochemical of dietary ginger, we found that 6-shogaol could induced both autophagic and apoptotic death in human colon adenocarcinoma (HT-29) cells. Results of this study showed that 6-shogal induced cell cycle arrest, autophagy, and apoptosis in HT-29 cells in a time sequence. After 6h, 6-shogal induced apparent G2/M arrest, then the HT-29 cells formed numerous autophagosomes in each phase of the cell cycle. After 18h, increases in acidic vesicles and LAMP-1 (Lysosome-associated membrane proteins 1) showed that 6-shogaol had caused autophagic cell death. After 24h, cell shrinkage and Caspase-3/7 activities rising, suggesting that apoptotic cell death had increased. And after 48h, the result of TUNEL assay indicated the highest occurrence of apoptosis upon 6-shogaol treatment. It appeared that apoptosis is triggered by autophagy in 6-shogaol treated HT-29 cells, the damage of autophagic cell death initiated apoptosis program.


Subject(s)
Adenocarcinoma/drug therapy , Apoptosis/drug effects , Autophagy/drug effects , Catechols/pharmacology , Cell Cycle Checkpoints/drug effects , Cell Death/drug effects , Colorectal Neoplasms/drug therapy , Adenocarcinoma/metabolism , Caspase 3/metabolism , Caspase 7/metabolism , Cell Line, Tumor , Colorectal Neoplasms/metabolism , G2 Phase Cell Cycle Checkpoints/drug effects , Zingiber officinale/chemistry , HT29 Cells , Humans , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
18.
Chem Commun (Camb) ; 48(63): 7847-9, 2012 Aug 14.
Article in English | MEDLINE | ID: mdl-22760299

ABSTRACT

We have successfully developed an example of copper-catalyzed decarboxylative C(sp(2))-C(sp(3)) coupling reactions via C-H functionalization for the first time. It is noteworthy that our catalytic system is very stable, low-cost, palladium-free, ligand-free, and easily accessible.

19.
J Neuroinflammation ; 9: 13, 2012 Jan 19.
Article in English | MEDLINE | ID: mdl-22257737

ABSTRACT

BACKGROUND: Intracerebral hemorrhage (ICH) remains a serious clinical problem lacking effective treatment. Urocortin (UCN), a novel anti-inflammatory neuropeptide, protects injured cardiomyocytes and dopaminergic neurons. Our preliminary studies indicate UCN alleviates ICH-induced brain injury when administered intracerebroventricularly (ICV). The present study examines the therapeutic effect of UCN on ICH-induced neurological deficits and neuroinflammation when administered by the more convenient intraperitoneal (i.p.) route. METHODS: ICH was induced in male Sprague-Dawley rats by intrastriatal infusion of bacterial collagenase VII-S or autologous blood. UCN (2.5 or 25 µg/kg) was administered i.p. at 60 minutes post-ICH. Penetration of i.p. administered fluorescently labeled UCN into the striatum was examined by fluorescence microscopy. Neurological deficits were evaluated by modified neurological severity score (mNSS). Brain edema was assessed using the dry/wet method. Blood-brain barrier (BBB) disruption was assessed using the Evans blue assay. Hemorrhagic volume and lesion volume were assessed by Drabkin's method and morphometric assay, respectively. Pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) expression was evaluated by enzyme-linked immunosorbent assay (ELISA). Microglial activation and neuronal loss were evaluated by immunohistochemistry. RESULTS: Administration of UCN reduced neurological deficits from 1 to 7 days post-ICH. Surprisingly, although a higher dose (25 µg/kg, i.p.) also reduced the functional deficits associated with ICH, it is significantly less effective than the lower dose (2.5 µg/kg, i.p.). Beneficial results with the low dose of UCN included a reduction in neurological deficits from 1 to 7 days post-ICH, as well as a reduction in brain edema, BBB disruption, lesion volume, microglial activation and neuronal loss 3 days post-ICH, and suppression of TNF-α, IL-1ß, and IL-6 production 1, 3 and 7 days post-ICH. CONCLUSION: Systemic post-ICH treatment with UCN reduces striatal injury and neurological deficits, likely via suppression of microglial activation and inflammatory cytokine production. The low dose of UCN necessary and the clinically amenable peripheral route make UCN a potential candidate for development into a clinical treatment regimen.


Subject(s)
Cerebral Hemorrhage/complications , Encephalitis/etiology , Nervous System Diseases/etiology , Neuroprotective Agents/administration & dosage , Urocortins/administration & dosage , Analysis of Variance , Animals , Blood Flow Velocity/drug effects , Blood Pressure/drug effects , Blood-Aqueous Barrier/drug effects , Brain/drug effects , Brain/pathology , Brain Edema/drug therapy , Brain Edema/etiology , CD11b Antigen/metabolism , Cell Count , Cerebral Hemorrhage/classification , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/pathology , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Cytokines/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Ectodysplasins/metabolism , Injections, Intraventricular , Laser-Doppler Flowmetry , Male , Phosphopyruvate Hydratase/metabolism , Rats , Rats, Sprague-Dawley , Severity of Illness Index , Time Factors
20.
J Neurosurg ; 116(1): 193-200, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21981644

ABSTRACT

OBJECT: Intracerebral hemorrhage (ICH) accounts for about 15% of all deaths due to stroke. It frequently causes brain edema, leading to an expansion of brain volume that exerts a negative impact on ICH outcomes. The ICH-induced brain edema involves inflammatory mechanisms. The authors' in vitro study shows that urocortin (UCN) exhibits antiinflammatory and neuroprotective effects. Therefore, the neuroprotective effect of UCN on ICH in rats was investigated. METHODS: Intracerebral hemorrhage was induced by an infusion of bacteria collagenase type VII-S or autologous blood into the unilateral striatum of anesthetized rats. At 1 hour after the induction of ICH, UCN (0.05, 0.5, and 5 µg) was infused into the lateral ventricle on the ipsilateral side. The authors examined the injury area, brain water content, blood-brain barrier permeability, and neurological function. RESULTS: The UCN, administered in the ipsilateral lateral ventricle, was able to penetrate into the injured striatum. Posttreatment with UCN reduced the injury area, brain edema, and blood-brain barrier permeability and improved neurological deficits of rats with ICH. CONCLUSIONS: Posttreatment with UCN through improving neurological deficits of rats with ICH dose dependently provided a potential therapeutic agent for patients with ICH or other brain injuries.


Subject(s)
Brain Edema/drug therapy , Brain/drug effects , Cerebral Hemorrhage/drug therapy , Neuroprotective Agents/therapeutic use , Urocortins/therapeutic use , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/pathology , Blood-Brain Barrier/physiopathology , Brain/physiopathology , Brain Edema/pathology , Brain Edema/physiopathology , Cerebral Hemorrhage/pathology , Cerebral Hemorrhage/physiopathology , Disease Models, Animal , Male , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Treatment Outcome , Urocortins/pharmacology
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