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1.
Artigo em Inglês | MEDLINE | ID: mdl-32423743

RESUMO

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway plays a pivotal role in abdominal aortic aneurysms (AAAs). However, systemic inhibition of this pathway causes serious side effects, thus limiting the clinical use of pan-PI3K inhibitors. In this study, it was hypothesised that the γ subunit of PI3K plays an important role in the PI3K/AKT signalling pathway during AAA, and that specifically targeting PI3Kγ may prevent this process. METHODS: Aortic specimens were collected from AAA patients and organ donors. Furthermore, a classical AAA model in male C57BL/6 mice was created via an intra-aortic porcine pancreatic elastase (PPE) infusion and aortas were collected. A specific PI3Kγ inhibitor, IPI-549, was administered to mice orally. The protein expression level of PI3Kγ was examined by immunohistochemistry and western blotting. The aortic leukocytes were examined by immunohistochemistry and flow cytometry. RESULTS: PI3Kγ protein levels were elevated in the aortas of AAA patients and PPE infused mice. Three color immunofluorescence staining revealed the predominant area of PI3Kγ by T cells and macrophages in aneurysmal aortas. IPI-549 treatment significantly prevented AAA formation in mice. Aortic macrophages, T cells and neo-angiogenesis were significantly reduced in mice treated with IPI-549 compared with vehicle treated PPE infused mice. Flow cytometry analysis also revealed that CD45+ leukocytes and CD45+ F4/80+ macrophages in IPI-549 treated mouse aortas decreased dramatically. Additionally, IPI-549 treatment inhibited the phosphorylation of AKT in experimental aneurysmal lesions. CONCLUSION: Specific inhibition of PI3Kγ limits AAA formation. Targeting PI3Kγ prevents inflammatory cell infiltration through inhibition of AKT phosphorylation in AAA.

2.
Biol Trace Elem Res ; 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32361885

RESUMO

The feasibility of using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) to overcome spectral overlaps in the determination of non-metallic elements was investigated. The contents of Si, P, S, Cl, Br, and I in herbal tea were determined by using ICP-MS/MS after microwave digestion. In the MS/MS mode, O2 and H2 were consecutively used as reaction gases. Low background equivalent concentration (BEC) and limit of detection (LOD) of analytes were obtained when using O2 mass shift, H2 mass shift, and H2 on-mass methods. The LODs for Si, P, S, Cl, Br, and I were 0.41, 0.048, 0.34, 0.76, 0.055, and 0.007 µg L-1, respectively. Standard reference materials NIST SRM 1515 (apple leaves) and NIST SRM 1547 (peach leaves) were used to evaluate the accuracy of the analytical method. The developed method was used to analyze 20 herbal teas. The ranges of values for Si, P, S, Cl, Br, and I in herbal tea were 236-4100, 1830-4360, 1290-3850, 335-4620, 0.86-8.21, and 0.091-0.65 µg g-1, respectively. The results showed that several non-metallic elements essential for the human body might be obtained by drinking herbal tea.

3.
Plant J ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32267570

RESUMO

The Arabidopsis MEKK1-MKK1/MKK2-MPK4 kinase cascade is monitored by the nucleotide-binding leucine-rich-repeat immune receptor SUMM2. Disruption of this kinase cascade leads to activation of SUMM2-mediated immune responses. MEKK2, a close paralog of MEKK1, is required for defense responses mediated by SUMM2, the molecular mechanism of which is unclear. In this study, we showed that MEKK2 serves as a negative regulator of MPK4. It binds to MPK4 to directly inhibit its phosphorylation by upstream MKKs. Activation of SUMM2-mediated defense responses induces the expression of MEKK2, which in turn blocks MPK4 phosphorylation to further amplify immune responses mediated by SUMM2. Intriguingly, MEKK2 locates in a tandem repeat consisting of MEKK1, MEKK2 and MEKK3, which was generated from a recent gene duplication event, suggesting that MEKK2 evolved from a MAPKKK to become a negative regulator of MAP kinases.

4.
Cell Host Microbe ; 27(5): 769-781.e6, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32234500

RESUMO

The Arabidopsis immune receptors RPS4 and RRS1 interact to co-confer responsiveness to bacterial effectors. The RRS1-R allele, with RPS4, responds to AvrRps4 and PopP2, whereas RRS1-S responds only to AvrRps4. Here, we show that the C terminus of RRS1-R but not RRS1-S is phosphorylated. Phosphorylation at Thr1214 in the WRKY domain maintains RRS1-R in its inactive state and also inhibits acetylation of RRS1-R by PopP2. PopP2 in turn catalyzes O-acetylation at the same site, thereby preventing its phosphorylation. Phosphorylation at other sites is required for PopP2 but not AvrRps4 responsiveness and facilitates the interaction of RRS1's C terminus with its TIR domain. Derepression of RRS1-R or RRS1-S involves effector-triggered proximity between their TIR domain and C termini. This effector-promoted interaction between these domains relieves inhibition of TIRRPS4 by TIRRRS1. Our data reveal effector-triggered and phosphorylation-regulated conformational changes within RRS1 that results in distinct modes of derepression of the complex by PopP2 and AvrRps4.

5.
Theranostics ; 10(10): 4395-4409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292503

RESUMO

Background: Circular RNAs (circRNAs) have been identified as essential regulators in a plethora of cancers. Nonetheless, the mechanistic functions of circRNAs in Renal Cell Carcinoma (RCC) remain largely unknown. Methods: In this study, we aimed to identify novel circRNAs that regulate RCC epithelial-mesenchymal transition (EMT), and to subsequently determine their regulatory mechanisms and clinical significance. Results: circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both in vitro and in vivo. We found that increased expression of circPRRC2A is positively associated with advanced clinical stage and worse survivorship in RCC patients. Mechanistically, our results indicate that circPRRC2A prevents the degradation of TRPM3, a tissue-specific oncogene, mRNA by sponging miR-514a-5p and miR-6776-5p. Moreover, circPRRC2A promotes tumor EMT and aggressiveness in patients with RCC. Conclusions: These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.

6.
Zootaxa ; 4750(1): zootaxa.4750.1.8, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32230057

RESUMO

In this paper, one new genus Paradoxitettigia gen. nov. is established and one new species Paradoxitettigia longicaudica sp. nov. is described. Furthermore, the morphological images of the new species are provided.


Assuntos
Ortópteros , Distribuição Animal , Animais , China
7.
BMC Plant Biol ; 20(1): 142, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252633

RESUMO

BACKGROUND: Reducing the dependence of crop production on chemical fertilizer with its associated costs, carbon footprint and other environmental problems is a challenge for agriculture. New solutions are required to solve this problem, and crop breeding for high nitrogen use efficiency or tolerance of low nitrogen availability has been widely considered to be a promising approach. However, the molecular mechanisms of high nitrogen use efficiency or low-nitrogen tolerance in crop plants are still to be elucidated, including the role of long non-coding RNAs (lncRNAs). RESULTS: In this study, we identified 498 lncRNAs in barley (Hordeum vulgare) landrace B968 (Liuzhutouzidamai), of which 487 were novel, and characterised 56 that were responsive to low-nitrogen stress. For functional analysis of differentially-expressed lncRNAs, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of co-expressed and co-located protein-coding genes were analyzed, and interactions with annotated co-expressed protein coding genes or micro RNAs (miRNAs) were further predicted. Target mimicry prediction between differentially-expressed lncRNAs and miRNAs identified 40 putative target mimics of lncRNAs and 58 target miRNAs. Six differentially-expressed lncRNAs were further validated by qPCR, and one in particular showed consistent differential expression using both techniques. Expression levels of most of the lncRNAs were found to be very low, and this may be the reason for the apparent inconsistency between RNA-seq and qPCR data. CONCLUSIONS: The analysis of lncRNAs that are differentially-expressed under low-nitrogen stress, as well as their co-expressed or co-located protein coding genes and target mimics, could elucidate complex and hitherto uncharacterised mechanisms involved in the adaptation to low-nitrogen stress in barley and other crop plants.

8.
Anal Chim Acta ; 1112: 1-7, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32334677

RESUMO

The occurrence and development of hepatocellular carcinoma (HCC) is related to the level of trace elements. The mechanism of changes in trace element concentration and the identification of HCC risks associated with them are not clear. Therefore, an accurate and reliable approach for quantification of the level of trace elements in the serum of liver cancer patients is of great significance. In this study, we proposed a novel strategy for accurate determination of trace elements such as Mn, Fe, Ni, Cu, Zn, and Se in the serum of HCC patients based on inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). In the MS/MS mode, N2O was used as the reaction gas, and an octopole reaction system (ORS) was employed to provide interference-free conditions and a sufficiently low limit of detection (LOD) for the determination of analytical elements. The internal standard elements with similar masses and similar mass spectrometry behavior were selected to correct the matrix effect. The LODs of Mn, Fe, Ni, Cu, Zn, and Se were as low as 0.013, 0.25, 0.010, 0.020, 0.17, and 0.008 µg L-1, respectively. Bovine serum (SRM 1598a) was adopted as the standard reference material to evaluate the accuracy of the method, and the developed method was successfully applied to determine the content of Mn, Fe, Cu, Zn, Ni, Se in serum from HCC patients. The obtained results were in agreement with that of sector field ICP-MS (SF-ICP-MS). The contents of Fe and Cu in the serum of HCC patients were higher compared to that of healthy controls, while the contents of Zn and Se were lower than that of healthy controls. Furthermore, no significant differences were observed in the contents of Mn and Ni in the serum of HCC patients and healthy controls.

9.
J Am Heart Assoc ; 9(8): e014757, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32308093

RESUMO

Background The protective effects of polyamines on cardiovascular disease have been demonstrated in many studies. However, the roles of spermidine, a natural polyamine, in abdominal aortic aneurysm (AAA) disease have not been studied. In this study, we investigated the influence and potential mechanisms of spermidine treatment on experimental AAA disease. Methods and Results Experimental AAAs were induced in 8- to 10-week-old male C57BL/6J mice by transient intra-aortic infusion of porcine pancreatic elastase. Spermidine was administered via drinking water at a concentration of 3 mmol/L. Spermidine treatment prevented experimental AAA formation with preservation of medial elastin and smooth muscle cells. In immunostaining, macrophages, T cells, neutrophils, and neovessels were significantly reduced in aorta of spermidine-treated, as compared with vehicle-treated elastase-infused mice. Additionally, flow cytometric analysis showed that spermidine treatment reduced aortic leukocyte infiltration and circulating inflammatory cells. Furthermore, we demonstrated that spermidine treatment promoted autophagy-related proteins in experimental AAAs using Western blot analysis, immunostaining, and transmission electron microscopic examination. Autophagic function was evaluated for human abdominal aneurysmal and nonaneurysmal adjacent aortae from AAA patients using Western blot analysis and immunohistochemistry. Dysregulated autophagic function, as evidenced by increased SQSTM1/p62 protein and phosphorylated mTOR, was found in aneurysmal, as compared with nonaneurysmal, aortic segments. Conclusions Our results suggest that spermidine supplementation limits experimental AAA formation associated with preserved aortic structural integrity, attenuated aortic inflammatory infiltration, reduced circulating inflammatory monocytes, and increased autophagy-related proteins. These findings suggest that spermidine may be a promising treatment for AAA disease.

10.
Photodiagnosis Photodyn Ther ; : 101748, 2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32294558

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is the most important representative pathogen which causes clinically relevant infections in diabetic ulceration. We report our investigations on the efficacy of antimicrobial photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) on diabetic murine infected wound models induced with a MRSA SA325 strain. A solution of 10% 5-aminolevulinic acid (ALA) was placed into the wounds followed by delivery of 25 J/cm2 (635 nm). The ALA-PDT treated wounds healed earlier as compared to others (P < 0.5). A significant reduction of bacterial counts (2.05 logs) was detected in wounds after ALA-PDT on Day 2 (P < 0.5). Additionally, histological analysis revealed that wounds treated with ALA-PDT exhibited a more complete re-epithelialization, blood micro-vessels, collagen-volume fraction and considerable decrease in inflammatory cells infiltration. Immunohistochemistry assay demonstrated considerable reduction of proinflammatory cytokines interleukin-1ß (IL-1ß), earlier expression of vascular endothelial growth factor A (VEGF-A), increase of basic fibroblast growth factor (bFGF) and Ki-67 in the ALA-PDT group (P < 0.5). These data imply that the therapeutic effect of ALA-PDT revealed an accelerated diabetic wound closure rate, together with reduced hyperinflammatory response and elevated growth factors.

11.
Int J Biol Macromol ; 154: 182-187, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32179116

RESUMO

Polysaccharide is the main active compound of Lilium, and showed many activities, such as hypoglycemic, antioxidant, immune-modulatory. There are three types' Lilium in China market, i.e. Lilium lancifolium Thunb (JD), Lilium davidiivar. Unicolor Salisb (L. davidii var)(LZBH), and Lilium brownii F.E. Brown var. viridulum Baker (BH). Near infrared spectroscopy (NIR) technique has become popular in the fields of quality control, due to its advantages, such as fast, non-destructive, and can detect several ingredients, simultaneously. In this study, a classification model was established based on NIR technique and random forest method to accurately distinguish three types' Lilium species, and the classification accuracy reached 94.37%. Furthermore, taking the effects of neighbor wavelength into account, a new weighted partial least square algorithm was proposed to establish an accurate and quantitative model for predicting the polysaccharide contents of these samples. In the model establishing process, some signal pre-treatment methods were optimized, and the validation results with highest determination coefficient (R2) and low root mean square errors of prediction (RMSEP) were, 0.9455 and 0.9098, respectively. The obtained results showed that combined NIR technique with chemometrics was an effective and green method for quality control.

12.
Int J Biol Sci ; 16(8): 1403-1416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210728

RESUMO

Baicalein (BA), a natural compound extracted from Scutellaria baicalensis Georgi, has been reported to exert antitumor effect in various cancers. However, the underlying mechanisms have not been well demonstrated. In the present study, we focused on the relationship between mitochondrial fission and BA-induced apoptosis and autophagy. We showed that BA inhibited cell viability and induced mitochondrial apoptosis in A549 and H1299 lung cancer cells. BA induced the loss of mitochondrial membrane potential (MMP) and the release of cytochrome c and apoptosis inducing factor (Aif) from mitochondria to cytoplasm. Meanwhile, BA induced autophagy and activated autophagic flux. Furthermore, we found that BA induced mitochondrial fission and mitochondrial impairment. Blocking mitochondrial fission by mdivi-1 attenuated BA-induced apoptosis and autophagy. Moreover, BA activated AMP-activated protein kinase (AMPK) pathway. Knockdown of AMPK with lentivirus encoded AMPKα also attenuated BA-induced mitochondrial fission, apoptosis and autophagy. Our in vivo data confirmed that BA inhibited tumor growth and induced apoptosis and autophagy in a Lewis lung carcinoma (LLC) xenograft model via activation of AMPK/mitochondrial fission pathway. Our study highlights the critical role of AMPK/mitochondrial fission pathway in the regulation of BA-induced apoptosis and autophagy. These results revealed the molecular mechanism of the anti-lung cancer property of BA and provided novel perspectives for the application of BA in the treatment of lung cancer.

13.
Eur J Pharmacol ; 876: 173032, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147435

RESUMO

In the present study, we established the acute lung injury (ALI) model of mice with adrenal insufficiency, and to investigate the possible mechanism by which Icariin (ICA) reduces lipopolysaccharide (LPS) -induced ALI in mice undergoing bilateral adrenalectomy by regulating glucocorticoid receptor α (GRα). ALI of BALB/c mice with adrenal insufficiency was induced by LPS and bilateral adrenalectomy (ADX). The pathological and morphological changes in lung tissues were observed, the levels of corticosterone, IL-6, and TNF-α in serum and lung tissues by ELISA. The levels of GRα, IL-6, TNF-α, NF-κB p65, Stat3, and c-Jun in lung tissues were detected by RT-qPCR and Western Blotting, GRα activity was blocked by GRα antagonist RU486. It was found that the dual intervention of LPS and ADX had further aggravation the downregulation of GRα and upregulation of NF-κB p65, c-Jun, Stat3, and IL-6 and TNF-α, ICA enhanced the expression of GRα in lung tissues and inhibited the expression of NF-κB p65, c-Jun, Stat3, IL-6, and TNF-ɑ, thereby reducing ALI. However, RU486 could partially counteract the protective effect of ICA on lung injury and its downregulating effect on various inflammatory transcription factors and inflammatory cytokines. In conclusion, ICA reduces ALI in mice undergoing bilateral ADX by regulating GRα, and no inhibitory effect on hypothalamic pituitary adrenal (HPA) axis.

15.
Nature ; 578(7794): 290-295, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32025034

RESUMO

Shear stress on arteries produced by blood flow is important for vascular development and homeostasis but can also initiate atherosclerosis1. Endothelial cells that line the vasculature use molecular mechanosensors to directly detect shear stress profiles that will ultimately lead to atheroprotective or atherogenic responses2. Plexins are key cell-surface receptors of the semaphorin family of cell-guidance signalling proteins and can regulate cellular patterning by modulating the cytoskeleton and focal adhesion structures3-5. However, a role for plexin proteins in mechanotransduction has not been examined. Here we show that plexin D1 (PLXND1) has a role in mechanosensation and mechanically induced disease pathogenesis. PLXND1 is required for the response of endothelial cells to shear stress in vitro and in vivo and regulates the site-specific distribution of atherosclerotic lesions. In endothelial cells, PLXND1 is a direct force sensor and forms a mechanocomplex with neuropilin-1 and VEGFR2 that is necessary and sufficient for conferring mechanosensitivity upstream of the junctional complex and integrins. PLXND1 achieves its binary functions as either a ligand or a force receptor by adopting two distinct molecular conformations. Our results establish a previously undescribed mechanosensor in endothelial cells that regulates cardiovascular pathophysiology, and provide a mechanism by which a single receptor can exhibit a binary biochemical nature.


Assuntos
Células Endoteliais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mecanotransdução Celular , Glicoproteínas de Membrana/metabolismo , Estresse Mecânico , Animais , Aterosclerose/metabolismo , Feminino , Integrinas/metabolismo , Camundongos , Neuropilina-1/metabolismo , Maleabilidade , Receptores de Superfície Celular/metabolismo , Semaforinas/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
Crit Rev Food Sci Nutr ; : 1-15, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957471

RESUMO

Gamma-tocopherol (γ-T), the major form of vitamin E in many plant seeds and products derived from them, has been attracting increasing attention because of its health-promoting roles. However, the underlying molecular mechanisms are still unclear, to some degree. Furthermore, its dimmers and quinones are expected to be potential nutritious and pharmaceutical agents, however, the knowledge about these dimmers (γ-TBD and γ-TED) and quinones (para- and ortho-quinones) is relatively limited. Thus, a comprehensive summary of the history, chemical structure, source, determination, absorption, transport, and metabolism of its dimmers and quinones compared to γ-T has been reviewed. In addition, the antioxidant activity (AOA) and non-AOA activity of these substances are highlighted. It is suggested that more special attention be paid to the dimmers and quinones for better understanding and further applications.

17.
Food Chem ; 312: 126041, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901829

RESUMO

Effect of fried food, oil type, moisture, fatty acid and molecular distribution on the effectiveness of rapid test of Total Polar Compounds (TPC) in frying oil based on dielectric constant was explored. Effects of all factors were compared and found to be significant (P < 0.05). Throughout the life cycle of frying oil, its rapid results were correlated well with those of conventional chromatography (Y = 0.7625X + 3.681, R2 = 0.8734). But the discrepancy was found within selected TPC ranges of 0%-10% and 20%-30%. According to the definition of TPC, three potential reasons for the high TPC values of fresh oils were discussed. For the deteriorated oils, the triglyceride dimers, mono-unsaturated and di-unsaturated fatty acids were found to be the main compositional factors by stepwise multivariate regression analysis. Pieces of advice about the operation guideline, internal control indices, calibration, reference oil, sensor, and detection range were proposed for instrument users and producers.


Assuntos
Óleos/química , Culinária , Ácidos Graxos/análise , Alimentos , Restaurantes , Fatores de Tempo , Triglicerídeos/análise
18.
Fish Shellfish Immunol ; 98: 887-898, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31770641

RESUMO

The aim of the present study was to investigate the function of the beta integrin (PmItgb) in Penaeus monodon. The 3011 bp cDNA sequence of PmItgb was cloned from P. monodon using rapid amplification of cDNA ends (RACE) PCR. Phylogenetic tree analyses indicated that the amino acid sequence of PmItgb should be merged into Fenneropenaeus chinensis (93%). Quantitative real-time PCR (q RT-PCR) revealed that PmItgb mRNA was highly expressed in the hemocytes. In addition, with regard to developmental stages, PmItgb showed significantly higher expression in oosperm, nauplius IV, zoea I and III, and post larval stages than that in other development stages. PmItgb expression in the shrimp epidermis was higher in the postmolt (B) stage, and lower in other molting stages. We also found that Vibrio harveyi and V. anguillarum challenge enhanced PmItgb expression in the hepatopancreas and gills. When PmItgb was inhibited, innate immunity-related genes such as ALF, crustin 1, crustin 7, penaeidin 3, and penaeidin 5 were significantly down-regulated. Furthermore, we demonstrated that PmItgb knock-down by specific dsRNA reduced bacterial clearance. In high ammonia nitrogen concentrations, PmItgb was significantly up-regulated in the hepatopancreas and gills. After PmItgb was silenced, the rate of mortality owing to high ammonia nitrogen concentrations decreased; the expression of related anti-apoptotic genes was up-regulated, and that of the apoptotic genes was slightly down-regulated. These results suggested that PmItgb may be involved in shrimp innate immunity and mediate apoptosis of hepatopancreatic cells induced by high ammonia nitrogen environments.

19.
J Ethnopharmacol ; 249: 112371, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683034

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Tiansui Formula (BSTSF) is a traditional Chinese medicine formula used clinically to treat Alzheimer's disease (AD) for many years. Previously, we have partially elucidated the mechanisms involved in the therapeutic effects of BSTSF on AD. However, the underlying mechanisms remain largely unclear. AIM OF THE STUDY: The aim of this study was to further investigate the therapeutic effects of BSTSF on AD using an integrated strategy of network pharmacology and serum metabolomics. MATERIALS AND METHODS: The rat models of AD were established using Aß 1-42 injection, and morris water maze test was used to evaluate the efficacy of BSTSF on AD. Next, network pharmacology analysis was applied to identify the active compounds and target genes, which might be responsible for the effect of BSTSF. Then, a metabolomics strategy has been developed to find the possible significant serum metabolites and metabolic pathway induced by BSTSF. Additionally, two parts of the results were integrated to confirm each other. RESULTS: The results of the network pharmacology analysis showed 37 compounds and 64 potential target genes related to the treatment of AD with BSTSF. The functional enrichment analysis indicated that the potential mechanism was mainly associated with the tumor necrosis factor signaling pathway and phosphatidylinositol 3 kinase/protein kinase B signaling pathway. Based on metabolomics, 78 differential endogenous metabolites were identified as potential biomarkers related to the BSTSF for treating AD. These metabolites were mainly involved in the relevant pathways of linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and arginine and proline metabolism. These findings were partly consistent with the findings of the network pharmacology analysis. CONCLUSIONS: In conclusion, our results solidly supported and enhanced out current understanding of the therapeutic effects of BSTSF on AD. Meanwhile, our work revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful means for identifying active components and mechanisms contributing to the pharmacological effects of traditional Chinese medicine.

20.
Mol Plant ; 13(1): 144-156, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31733371

RESUMO

Two signal molecules, salicylic acid (SA) and N-hydroxypipecolic acid (NHP), play critical roles in plant immunity. The biosynthetic genes of both compounds are positively regulated by master immune-regulating transcription factors SARD1 and CBP60g. However, the relationship between the SA and NHP pathways is unclear. CALMODULIN-BINDING TRANSCRIPTION FACTOR 1 (CAMTA1), CAMTA2, and CAMTA3 are known redundant negative regulators of plant immunity, but the underlying mechanism also remains largely unknown. In this study, through chromatin immunoprecipitation and electrophoretic mobility shift assays, we uncovered that CBP60g is a direct target of CAMTA3, which also negatively regulates the expression of SARD1, presumably via an indirect effect. The autoimmunity of camta3-1 is suppressed by sard1 cbp60g double mutant as well as ald1 and fmo1, two single mutants defective in NHP biosynthesis. Interestingly, a suppressor screen conducted in the camta1/2/3 triple mutant background yielded various mutants blocking biosynthesis or signaling of either SA or NHP, leading to nearly complete suppression of the extreme autoimmunity of camta1/2/3, suggesting that the SA and NHP pathways can mutually amplify each other. Together, these results reveal that CAMTAs repress the biosynthesis of SA and NHP by modulating the expression of SARD1 and CBP60g, and that the SA and NHP pathways are coordinated to optimize plant immune response.

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