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This paper introduces Professor WANG Haidong's approach to treat cervical vertigo with needle knife based on the holism of body-qi-spirit. Professor WANG Haidong, considering the etiology and pathogenesis of cervical vertigo, starting from the holism of body-qi-spirit, based on the anatomical structure, employs the "seven-neck points" technique to improve local blood supply and address the physical issue; guided by the Jingjin theory, he utilizes the "knot releasing technique" to disperse knots and relax sinews, thereby regulating qi. In addition, he uses the "bone puncturing technique at governor vessel" to uplift yang-qi and nourish the brain, thereby nurturing the spirit.
Subject(s)
Acupuncture Therapy , Vertigo , Humans , Vertigo/therapy , Acupuncture Therapy/instrumentation , Acupuncture Therapy/methods , Qi , Male , Acupuncture Points , FemaleABSTRACT
The effect of anoikis-related genes (ARGs) on clinicopathological characteristics and tumor microenvironment remains unclear. We comprehensively analyzed anoikis-associated gene signatures of 1057 colorectal cancer (CRC) samples based on 18 ARGs. Anoikis-related molecular subtypes and gene features were identified through consensus clustering analysis. The biological functions and immune cell infiltration were assessed using the GSVA and ssGSEA algorithms. Prognostic risk score was constructed using multivariate Cox regression analysis. The immunological features of high-risk and low-risk groups were compared. Finally, DAPK2-overexpressing plasmid was transfected to measure its effect on tumor proliferation and metastasis in vitro and in vivo. We identified 18 prognostic ARGs. Three different subtypes of anoikis were identified and demonstrated to be linked to distinct biological processes and prognosis. Then, a risk score model was constructed and identified as an independent prognostic factor. Compared to the high-risk group, patients in the low-risk group exhibited longer survival, higher enrichment of checkpoint function, increased expression of CTLA4 and PD-L1, higher IPS scores, and a higher proportion of MSI-H. The results of RT-PCR indicated that the expression of DAPK2 mRNA was significantly downregulated in CRC tissues compared to normal tissues. Increased DAPK2 expression significantly suppressed cell proliferation, promoted apoptosis, and inhibited migration and invasion. The nude mice xenograft tumor model confirmed that high expression of DAPK2 inhibited tumor growth. Collectively, we discovered an innovative anoikis-related gene signature associated with prognosis and TME. Besides, our study indicated that DAPK2 can serve as a promising therapeutic target for inhibiting the growth and metastasis of CRC.
Subject(s)
Anoikis , Colorectal Neoplasms , Immunotherapy , Tumor Microenvironment , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Anoikis/genetics , Animals , Prognosis , Mice , Immunotherapy/methods , Female , Male , Gene Expression Regulation, Neoplastic , Death-Associated Protein Kinases/genetics , Cell Line, Tumor , Biomarkers, Tumor/genetics , Mice, Nude , Transcriptome , Gene Expression Profiling , Xenograft Model Antitumor Assays , Middle Aged , Cell Proliferation/genetics , Mice, Inbred BALB CABSTRACT
The ripening characteristics after capping of honey are favourable for improving its quality. However, research on the variation and formation of aroma characteristics of honey in this process is lacking. Therefore, the present study was carried out with different stages of Rhus chinensis honeys (RCHs) after capping and identified 192 volatiles with varying levels of concentration. "Fruity" was the main aroma characteristic of RCHs at different stages after capping, mainly contributed by (E)-ß-damascenone. Methyl salicylate might be a potential indicator for differentiating RCHs at different stages after capping. The metabolic pathway analyses revealed that the aroma compounds in RCHs undergo transformation at different stages after capping, which subsequently affects its aroma characteristics formation. This work is the first to study the dynamic changes in honey aroma characteristics after capping from multiple perspectives, and the results are of great significance for understanding the aroma characteristics after capping and quality control of honey.
Subject(s)
Honey , Odorants , Rhus , Volatile Organic Compounds , Honey/analysis , Odorants/analysis , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/analysis , Rhus/chemistry , Gas Chromatography-Mass Spectrometry , Food Handling , Quality ControlABSTRACT
The quest for high-performance piezoelectric materials has been synonymous with the pursuit of the morphotropic phase boundary (MPB), yet the full potential of MPBs remains largely untapped outside of the realm of ferroelectrics. In this study, we reveal a new class of MPB by creating continuous molecular-based solid solutions between centro- and noncentrosymmetric compounds, exemplified by (tert-butylammonium)1-x(tert-amylammonium)xFeCl4 (0 ≤ x ≤ 1), where the MPB is formed due to disorder of molecular cations. Near the MPB, we discovered an exceptionally sensitive nonlinear optical material in the centrosymmetric phase, capable of activation at pressures as low as 0.12-0.27 GPa, and producing tunable second-harmonic generation (SHG) signals from zero to 18.8 times that of KH2PO4 (KDP). Meanwhile, synchrotron diffraction experiments have unveiled a third competing phase (P212121) appearing at low pressure, forming a triple-phase point near the MPB, thereby providing insight into the mechanism underpinning the nonlinear optical (NLO) switch behavior. These findings highlight the opportunity to harness exceptional physical properties in symmetry-breaking solid solution systems by strategically designing novel MPBs.
ABSTRACT
In this work, to promote the separation of photogenerated carriers, prevent the catalyst from photo-corrosion, and improve the photo-Fenton synergistic degradation of organic pollutants, the coating structure of FeOOH/BiO2-x rich in oxygen vacancies was successfully synthesized by a facile and environmentally friendly two-step process of hydrothermal and chemical deposition. Through a series of degradation activity tests of synthesized materials under different conditions, it was found that FeOOH/BiO2-x demonstrated outstanding organic pollutant degradation activity under visible and near-infrared light when hydrogen peroxide was added. After 90 min of reaction under photo-Fenton conditions, the degradation rate of Methylene Blue by FeOOH/BiO2-x was 87.4%, significantly higher than the degradation efficiency under photocatalysis (60.3%) and Fenton (49.0%) conditions. The apparent rate constants of FeOOH/BiO2-x under photo-Fenton conditions were 2.33 times and 3.32 times higher than photocatalysis and Fenton catalysis, respectively. The amorphous FeOOH was tightly coated on the layered BiO2-x, which significantly increased the specific surface area and the number of active sites of the composites, and facilitated the improvement of the separation efficiency of the photogenerated carriers and the prevention of photo-corrosion of BiO2-x. The analysis of the mechanism of photo-Fenton synergistic degradation clarified that ·OH, h+, and ·O2- are the main active substances involved in the degradation of pollutants. The optimal degradation conditions were the addition of the FeOOH/BiO2-x composite catalyst loaded with 20% Fe at a concentration of 0.5 g/L, the addition of hydrogen peroxide at a concentration of 8 mM, and an initial pH of 4. This outstanding catalytic system offers a fresh approach to the creation and processing of iron-based photo-Fenton catalysts by quickly and efficiently degrading various organic contaminants.
ABSTRACT
Cuproptosis, a recently characterized programmed cell death mechanism, has emerged as a potential contributor to tumorigenesis, metastasis, and immune modulation. Long non-coding RNAs (lncRNAs) have demonstrated diverse regulatory roles in cancer and hold promise as biomarkers. However, the involvement and prognostic significance of cuproptosis-related lncRNAs (CRLs) in oral squamous cell carcinoma (OSCC) remain poorly understood. Based on TCGA-OSCC data, we integrated single-sample gene set enrichment analysis (ssGSEA), the LASSO algorithm, and the tumor immune dysfunction and exclusion (TIDE) algorithm. We identified 11 CRLs through differential expression, Spearman correlation, and univariate Cox regression analyses. Two distinct CRL-related subtypes were unveiled, delineating divergent survival patterns, tumor microenvironments (TME), and mutation profiles. A robust CRL-based signature (including AC107027.3, AC008011.2, MYOSLID, AC005785.1, AC019080.5, AC020558.2, AC025265.1, FAM27E3, and LINC02367) prognosticated OSCC outcomes, immunotherapy responses, and anti-tumor strategies. Superior predictive power compared to other lncRNA models was demonstrated. Functional assessments confirmed the influence of FAM27E3, LINC02367, and MYOSLID knockdown on OSCC cell behaviors. Remarkably, the CRLs-based signature maintained stability across OSCC patient subgroups, underscoring its clinical potential for survival prediction. This study elucidates CRLs' roles in TME of OSCC and establishes a potential signature for precision therapy.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/therapy , RNA, Long Noncoding/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/therapy , Immunotherapy , Apoptosis , Tumor Microenvironment/geneticsABSTRACT
BACKGROUND: Aroma is one of the most important quality criterion of different honeys and even defines their merchant value. The composition of volatile compounds, especially the characteristic odor-active compounds, contributes significantly to the aroma of honey. Evodia rutaecarpa (Juss) Benth honey (ERBH) is a special honey in China with unique flavor characteristics. However, no work in the literature has investigated the volatile compounds and characteristic odor-active compounds of ERBHs. Therefore, it is imperative to conduct systematic investigation into the volatile profile, odor-active compounds and odor properties of ERBHs. RESULTS: The characteristic fingerprint of ERBHs was successfully constructed with 12 characteristic peaks and a similarity range of 0.785-0.975. In total, 297 volatile compounds were identified and relatively quantified by headspace solid-phase microextraction coupled with gas chromatography quadrupole time-of-flight mass spectrometry, of which 61 and 31 were identified as odor-active compounds by relative odor activity values and GC-olfactometry analysis, respectively, especially the common 22 odor-active compounds (E)-ß-damascenone, phenethyl acetate, linalool, cis-linalool oxide (furanoid), octanal, hotrienol, trans-linalool oxide (furanoid), 4-oxoisophorone and eugenol, etc., contributed significantly to the aroma of ERBHs. The primary odor properties of ERBHs were floral, followed by fruity, herbaceous and woody aromas. The partial least-squares regression results showed that the odor-active compounds had good correlations with the odor properties. CONCLUSION: Identifying the aroma differences of different honeys is of great importance. The present study provides a reliable theoretical basis for the quality and authenticity of ERBHs. © 2023 Society of Chemical Industry.
Subject(s)
Acyclic Monoterpenes , Cyclohexanols , Evodia , Honey , Trityl Compounds , Volatile Organic Compounds , Odorants/analysis , Evodia/chemistry , Honey/analysis , Gas Chromatography-Mass Spectrometry/methods , Volatile Organic Compounds/chemistryABSTRACT
Dendropanax dentiger honey (DDH) is a specialty herbal honey from China. Previous research on DDH has mostly focused on its composition and potential chemical markers, no studies have been conducted on the changes in aroma characteristics and chiral odorants during its maturation. Therefore, the present study aims to address the missing parts. The proportions and total concentrations of 185 volatile compounds identified in different classes varied with DDHs ripening. Fourteen common odor-active compounds were identified by odor activity values (OAVs) and GC-olfactometry (GC-O) analysis. The aroma profiles of DDHs were observed to vary at different ripening stages, although the dominant aroma characteristic was "fruity" aroma, which became more pronounced with increasing maturity. The enantiomeric contents and distributions of 7 volatile enantiomers were related to specific physicochemical indicators and the maturity of DDHs, among which the enantiomers of linalool oxide A may be a potential indicator to identify its maturity. Furthermore, precise quantification and OAVs calculation showed that the enantiomer (2S, 5S)-linalool oxide A presented the highest concentration (8.83-27.39 ng/mL) and only the enantiomer R-linalool (OAVs: 5.56-6.14) was an important contributor to the aroma profiles of DDHs at different stages of maturity. These results provided a new research idea for quality control and identification of DDHs at different maturity stages.
Subject(s)
Honey , Volatile Organic Compounds , Gas Chromatography-Mass Spectrometry/methods , Honey/analysis , Volatile Organic Compounds/analysis , Odorants/analysisABSTRACT
It is crucial to monitor the authenticity of royal jelly (RJ) because the qualities of RJs produced by different floral periods vary substantially. In the context of non-migratory beekeeping, this study aims to identify rape RJ (RRJ), chaste RJ (CRJ), and sesame RJ (SRJ) based on δ13C, δ15N, δ2H, and δ18O combined with machine learning and to evaluate environmental effect factors. The results showed that δ13C (-27.62 ± 0.24), δ15N (2.88 ± 0.85), and δ18O (28.02 ± 1.30) of RRJ were significantly different from other RJs. The δ13C, δ2H, and δ18O in CRJ and SRJ were strongly correlated with temperature and precipitation, suggesting that these isotopes are influenced by environmental elements such as sunlight and rainfall. In addition, the artificial neural network (ANN) model was superior to the random forest (RF) model in terms of accuracy, sensitivity, and specificity. This study revealed that combining stable isotopes with ANN models and the unique correlation between stable isotopes and environmental factors could provide promising ideas for monitoring the authenticity of RJ.
Subject(s)
Beekeeping , Isotopes , Fatty Acids , TemperatureABSTRACT
The BiS2 -based layered superconductors with structures similar to those of cuprates and iron-based superconductors have stimulated much research interest. Here, a new quaternary compound is reported, Bi5 O4 S3 Cl, which crystalizes in a tetragonal structure with P4/mmm (No. 123) space group having alternately stacking unique BiS3 layers and Bi2 O2 layers along the c-axis with a Cl atom located at the center of the unit cell. A superconducting transition above 3 K is observed for both electrical transport and magnetic measurements. Hall resistivity measurements show its multiband character with a conduction dominated by electron-like charge carriers. The first-principles calculations exhibit that the semiconducting parent phase Bi5 O4 S3 Cl becomes metallic when sulfur vacancies are introduced, which hints the origin of superconductivity in Bi5 O4 S3 Cl. The findings will inspire the exploration of new BiS-based superconductors.
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We herein report the first visible-light-induced hydromono- and difluoroalkylations of alkenes with inexpensive and easily accessible α-fluoro carboxylic acids. This metal-free protocol exhibits mild conditions, high efficiency, and excellent functional-group tolerance, providing a straightforward approach to mono- and difluoroalkylated alkanes. Moreover, the fluorine effect on the hydrofluoroalkylation reaction is discussed in detail.
ABSTRACT
A mild and efficient method for direct C-H monofluoroalkylation of heteroarenes with easily accessible and inexpensive α-fluorocarboxylic acids has been developed. This silver-catalyzed reaction affords mono- and bis-monofluoroalkylated heteroarenes in good yields under mild conditions, and the solvent effect on the monofluoroalkylation reaction is discussed in detail.
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@#[Abstract] Objective: To investigate the effects of fibronectin Ⅲ domain containing protein 10 (FNDC10) on the proliferation, migration and invasion of breast cancer cells, and to primarily explore the mechanism. Methods: TCGA database was used to analyze the expression of FNDC10 in breast cancer tissues. The mRNA level of FNDC10 in normal immortalized breast cells (MCF-10A) and breast cancer cells (MCF-7, MDA-MB-231, BT549, MDA-MB-468, HCC1806, HCC1937) was detected by qPCR. MCF-7 and MDA-MB-231 cells were transfected with FNDC10 siRNA or NC-siRNA for functional experiments. CCK-8 assay was used to detect the effect of FNDC10 on the proliferation of breast cancer cells. Colony forming assay was used to detect the colony forming ability of breast cancer cells. Transwell assay was used to detect the effect of FNDC10 on migration and invasion of breast cancer cells. WB was used to detect the changes of metastasis-related molecules and cell signaling pathways at protein level. Results:The expression of FNDC10 in breast cancer tissues was significantly higher than that in normal tissues (P<0.01), and the expression level of FNDC10 in breast cancer MCF-7 and MDA-MB-231 cells was higher than that in normal breast cells (P<0.01 or P<0.05). Knocking down FNDC10 expression inhibited the proliferation, migration and invasion of breast cancer cells (P<0.01 or P<0.05). The mechanism study showed that knockdown of FNDC10 expression inhibited STAT3 activation in breast cancer cells (P<0.01 or P<0.05) and enhanced the expression of EMT maker E-cadherin (P<0.05), leading to the suppression of EMT progression. Conclusion: FNDC10 promotes proliferation and EMT of breast cancer cells through activating STAT3 signaling pathway, thereby promoting the malignant progression of breast cancer.
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Objective To investigate the role of nuclear receptor-binding SET domain protein 3 (NSD3) in lipopolysaccharide (LPS)-triggered tumor necrosis factor α (TNF-α) production in macrophages and the underlying epigenetic mechanism. Methods The experiment used murine peritoneal macrophages and RAW264.7 cells as cell models. The mRNA and protein level of NSD3 were detected by real-time quantitative PCR and Western blot analysis in mouse peritoneal macrophages stimulated with LPS (100 ng/mL). ELISA was used to detect the production of TNF-α in NSD3-overexpressing RAW264.7 cells or NSD3-silencing peritoneal macrophages. Western blot analysis was performed to test the activation of LPS-triggered NF-κBp65 in NSD3-silencing macrophages. Luciferase assay was used to assess NF-κBp65-mediated transcriptional activation of TNF-α gene. ChIP assay was used to detect the recruitment of H3K36 methylation to TNF-α gene promoter. Results LPS inhibited the expression of NSD3 in the macrophages. Over-expression of NSD3 suppressed LPS-triggered TNF-α production, and silencing NSD3 promoted LPS-triggered TNF-α production. However, NSD3 had no effect on the activation of LPS-triggered NF-κBp65. NSD3 enhanced NF-κBp65-mediated transcriptional activation of TNF-α gene. NSD3 enhanced the dimethylation of H3K36 of TNF-α gene promoter. Conclusion NSD3 can promote the dimethylation of H3K36 of TNF-α gene promoter and suppress TNF-α transcription and production.
Subject(s)
Histone-Lysine N-Methyltransferase/metabolism , Histones/chemistry , Macrophages/metabolism , Nuclear Proteins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Gene Silencing , Lipopolysaccharides , Methylation , Mice , RAW 264.7 Cells , Transcription Factor RelA/metabolismABSTRACT
ASF1a (anti-silencing function 1a), an evolutionarily conserved protein and a histone chaperone, is required for a variety of chromatin-mediated cellular processes. However, the function of ASF1a in innate immune response remains unclear. Here, we find that ASF1a is induced in Vesicular Stomatitis Virus (VSV)-infected macrophages in a manner that is dependent on IRF3 signal. ASF1a promotes VSV-triggered IFN-ß production. Moreover, acetylation of H3K56 increases at the ifnb promoter after VSV infection, which is dependent on ASF1a. Furthermore, we find ASF1a-mediated H3K56ac is dependent on the acetyltransferases activity of CREB binding protein (CBP) and the association between ASF1a and CBP. Therefore, our work provides a new insight into the antiviral mechanism that histone chaperone ASF1a-mediated H3K56ac modification promotes IFN-ß production.
Subject(s)
Cell Cycle Proteins/immunology , Chromosomal Proteins, Non-Histone/immunology , Gene Expression Regulation/immunology , Interferon-beta/biosynthesis , Membrane Proteins/immunology , Phosphoproteins/immunology , Vesicular Stomatitis/immunology , Acetylation , Animals , Chromatin Immunoprecipitation , Gene Knockdown Techniques , HEK293 Cells , Histones/genetics , Histones/metabolism , Humans , Immunoblotting , Immunoprecipitation , Interferon-beta/genetics , Interferon-beta/immunology , Macrophages/immunology , Macrophages/virology , Mice , Mice, Inbred C57BL , Polymerase Chain Reaction , Promoter Regions, Genetic , Vesicular stomatitis Indiana virus/immunologyABSTRACT
Identifying prognostic factors for osteosarcoma (OS) aids in the selection of patients who require more aggressive management. XB130 is a newly characterized adaptor protein that was reported to be a prognostic factor of certain tumor types. However, the association between XB130 expression and the prognosis of OS remains unknown. In the present study, we investigated the association between XB130 expression and clinicopathologic features and prognosis in patients suffering OS, and further investigated its potential role on OS cells in vitro and vivo. A retrospective immunohistochemical study of XB130 was performed on archival formalin-fixed paraffin-embedded specimens from 60 pairs of osteosarcoma and noncancerous bone tissues, and compared the expression of XB130 with clinicopathological parameters. We then investigate the effect of XB130 sliencing on invasion in vitro and lung metastasis in vivo of the human OS cell line. Immunohistochemical assays revealed that XB130 expression in OS tissues was significantly higher than that in corresponding noncancerous bone tissues (P=0.001). In addition, high XB130 expression more frequently occurred in OS tissues with advanced clinical stage (P=0.002) and positive distant metastasis (P=0.001). Moreover, OS patients with high XB130 expression had significantly shorter overall survival and disease-free survival (both P<0.001) when compared with patients with the low expression of XB130. The univariate analysis and multivariate analysis shown that high XB130 expression and distant metastasis were the independent poor prognostic factor.We showed that XB130 depletion by RNA interference inhibited invasion of XB130-rich U2OS cells in vitro and lung metastasis in vivo. This is the first study to reveal that XB130 overexpression may be related to the prediction of metastasis potency and poor prognosis for OS patients, suggesting that XB130 may serve as a prognostic marker for the optimization of clinical treatments. Furthermore, XB130 is the potential molecular target for OS therapy.
Subject(s)
Adaptor Proteins, Signal Transducing/biosynthesis , Biomarkers, Tumor/analysis , Bone Neoplasms/pathology , Osteosarcoma/pathology , Adolescent , Adult , Animals , Blotting, Western , Bone Neoplasms/metabolism , Bone Neoplasms/mortality , Child , Disease-Free Survival , Female , Heterografts , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Mice , Mice, Nude , Osteosarcoma/metabolism , Osteosarcoma/mortality , Prognosis , Proportional Hazards Models , Retrospective Studies , Transfection , Young AdultABSTRACT
Ahead of Print article withdrawn by publisher.
ABSTRACT
Calcium/calmodulindependent protein kinase II (CaMKII) is a multi-functional serine/threonine protein kinase, involved in processes that cause tumor progression, including cell cycle regulation, apoptosis and differentiation. However, the role of CaMKII in cancer cell metastasis has not been fully elucidated. In the present study, the function of CaMKII in gastric cancer cell metastasis is reported. Firstly, it was demonstrated that the overexpression of H282R (constitutively active CaMKII) enhanced gastric cancer cell migration and invasion, and the inhibition of CaMKII activity by KN62 decreased gastric cancer cell metastasis. Furthermore, H282R upregulated matrix metalloproteinase9 (MMP9) expression and production, which were dependent on CaMKIImediated increase in nuclear factor (NF)κB and Akt activation. Finally, CaMKII activation, through phosphorylation of the Thr 286 site, was significantly increased in the metastatic gastric cancer tissues compared with nonmetastatic tissues, suggesting that CaMKII has an important function in the regulation of gastric cancer cell metastasis. Collectively, the present study demonstrated that CaMKII promotes gastric cancer cell metastasis by NFκB and AktmediatedMMP9 production. These findings suggest a novel function of CaMKII in the control of gastric cancer metastasis, offering a promising target for future therapeutics to treat and prevent gastric cancer metastases via the inhibition of CaMKII activity.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/physiology , Matrix Metalloproteinase 9/metabolism , Stomach Neoplasms/enzymology , Cell Line, Tumor , Enzyme Induction , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Matrix Metalloproteinase 9/genetics , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/pathology , Up-RegulationABSTRACT
Multiple signaling pathways are involved in the tight regulation of Toll-like receptor (TLR) signaling, which is important for the tailoring of inflammatory response to pathogens in macrophages. It is widely accepted that TLR signaling can activate Notch pathway; however, whether full activation of Notch signaling can feedback modulate TLR signaling pathway so as to control inflammation response remains unclear. Here, we demonstrated that stimulation with TLR ligands up-regulated Notch1 and Notch2 expression in macrophages. The expression of Notch target genes including Hes1 and Hes5 was also induced in macrophages by LPS, suggesting that TLR4 signaling enhances the activation of Notch pathway. Importantly, overexpression of constituted active form of Notch1 (NICD1) and Notch2 (NICD2) suppressed production of TLR4-triggered proinflammatory cytokines such as TNF-α and IL-6 but promoted production of antiinflammatory cytokine IL-10, which is dependent on the PEST domain of NICD. In addition, NICD1 and NICD2 suppressed TLR-triggered ERK phosphorylation, which is indispensable for Notch-mediated inhibition of TLR4-triggered proinflammatory cytokine production. Furthermore, activation of Notch signaling inhibited NF-κB transcription activity by MyD88/TRAF6 and TRIF pathways, which was dependent on ERK activity. Therefore, our results showed that Notch signaling negatively regulates TLR-triggered inflammation responses, revealing a new mechanism for negative regulation of TLR signaling via Notch pathway.
Subject(s)
MAP Kinase Signaling System/physiology , Macrophages, Peritoneal/metabolism , NF-kappa B/metabolism , Receptor, Notch1/metabolism , Receptor, Notch2/metabolism , Toll-Like Receptors/metabolism , Adaptor Proteins, Vesicular Transport/metabolism , Animals , Cytokines/immunology , Cytokines/metabolism , HEK293 Cells , Humans , Inflammation/immunology , Inflammation/metabolism , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/immunology , Mice , Mice, Inbred C57BL , Myeloid Differentiation Factor 88/metabolism , Receptor, Notch1/immunology , Receptor, Notch2/immunology , TNF Receptor-Associated Factor 6/metabolism , Toll-Like Receptors/immunology , Up-Regulation/immunologyABSTRACT
This paper studied the effects of 0.3 mmol x L(-1) SNP on the antioxidant enzymes and reactive oxygen in pear leaves infected by Physalosproa piricola Nose. The results showed that compared with CK1 (spraying leaves with water and infecting with P. piricola Nose), 0.3 mmol x L(-1) SNP could increase the activities of leaf POD, SOD, CAT and PPO and the contents of leaf ASA, GSH and proline by 39.41%, 21.11%, 41.61%, 13.04%, 44.45%, 48.32% and 33.80%, while decrease the contents of leaf MDA and H2O2 and the generating rate of O2- by 20.45%, 6.93% and 6.27%, respectively, indicating that lower concentration SNP could reduce the damage of P. piricola Nose to pear leaves.