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1.
Front Immunol ; 15: 1366377, 2024.
Article in English | MEDLINE | ID: mdl-38566992

ABSTRACT

Interleukin-27 (IL-27) is a member of the IL-12 family. The gene encoding IL-27 is located at chromosome 16p11. IL-27 is considered as a heterodimeric cytokine, which consists of Epstein-Barr virus (EBV)-induced gene 3 (Ebi3) and IL-27p28. Based on the function of IL-27, it binds to receptor IL-27rα or gp130 and then regulates downstream cascade. To date, findings show that the expression of IL-27 is abnormal in different inflammatory autoimmune diseases (including systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, Behcet's disease, inflammatory bowel disease, multiple sclerosis, systemic sclerosis, type 1 diabetes, Vogt-Koyanagi-Harada, and ankylosing spondylitis). Moreover, in vivo and in vitro studies demonstrated that IL-27 is significantly in3volved in the development of these diseases by regulating innate and adaptive immune responses, playing either an anti-inflammatory or a pro-inflammatory role. In this review, we comprehensively summarized information about IL-27 and autoimmunity based on available evidence. It is hoped that targeting IL-27 will hold great promise in the treatment of inflammatory autoimmune disorders in the future.


Subject(s)
Autoimmune Diseases , Epstein-Barr Virus Infections , Interleukin-27 , Humans , Interleukin-27/genetics , Herpesvirus 4, Human , Autoimmunity
2.
Zhongguo Gu Shang ; 37(4): 363-7, 2024 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-38664206

ABSTRACT

OBJECTIVE: To investigate the satisfaction of patients with Crowe Ⅲ-Ⅳ developmental dysplasia of the hip(DDH) after total hip arthroplasty and the related factors. METHODS: A retrospective study included 169 patients with Crowe type Ⅲ-Ⅳ DDH who underwent total hip arthroplasty between March 2013 and March 2018. Patients were surveyed through WeChat, covering overall satisfaction with the operation, satisfaction with ten daily functions, and the top five questions perceived to have a great impact on daily life. Preoperative and postoperative hip function was evaluated by Harris score. RESULTS: One hundred and forty-five questionnaires were received, with a follow-up period ranging from 1 to 5 years with an average of (3.23±1.22) years. Among these patients, 118 patients were satisfied with the surgical outcomes, while 27 patients were dissatisfied, with the overall satisfaction rate of 81.38%(118/145). The top five problems affecting patient life were postoperative hip pain, limb length discrepancy, walking, stair climbing, and squatting. There were no statistical differences in age, sex, body mass index, preoperative Harris scores (P>0.05). However, the dissatisfied group had lower postoperative Harris scores. Postoperative hip pain and limb length discrepancy were identified as direct factors contributing to postoperative surgical dissatisfaction. CONCLUSION: Total hip arthroplasty for patients with Crowe type Ⅲ-Ⅳ DDH is challenging. Postoperative hip pain (mild or severe) and limb length discrepancy (>2 cm) are independent risk factors for postoperative dissatisfaction.


Subject(s)
Arthroplasty, Replacement, Hip , Developmental Dysplasia of the Hip , Patient Satisfaction , Humans , Female , Male , Middle Aged , Developmental Dysplasia of the Hip/surgery , Retrospective Studies , Aged , Adult , Surveys and Questionnaires
4.
Int Immunopharmacol ; 126: 111272, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38006754

ABSTRACT

OBJECTIVE: Relationship between neuropeptide Y (NPY) serum levels, NPY genetic mutation with systemic lupus erythematosus (SLE) pathogenesis is yet to be clarified, and role of NPY in development of SLE needs elucidation. METHOD: This study included 460 SLE patients, 472 non-SLE cases, 500 healthy volunteers. Serum NPY, matrix metalloproteinase-1 (MMP-1) and MMP-8 levels were tested by ELISA. Genotyping 7 NPY single nucleotides polymorphisms (SNPs) (rs5573, rs5574, rs16129, rs16138, rs16140, rs16147, rs16478) was obtained by Kompetitive Allele-Specific PCR (KASP) method. Pristane-induced lupus mice were treated with NPY-Y1 receptor antagonist, and histological analysis, serological changes of the mice were evaluated. RESULTS: NPY serum concentrations were significantly increased in SLE patients when compared to that in healthy volunteers, non-SLE cases. Rs5573 G allele, rs16129 T allele, rs16147 G allele frequencies were significantly different between SLE cases and healthy controls. Rs5574 TT + TC genotypes were related to levels of IgG, C3, C4 and erythrocyte sedimentation rate, and rs16138 GG + GC genotypes correlated with SLE cases with anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA) (+). Serum MMP-1, MMP-8 concentrations were higher in SLE patients, and NPY levels were significantly related to MMP-1, MMP-8 levels. After treatment of lupus mice with NPY-Y1 receptor antagonist, damage of liver, spleen and kidney was alleviated, production of autoantibodies (anti-nuclear antibody (ANA), total IgG, anti-dsDNA) and MMP-1, MMP-8 was down-regulated, and differentiation of CD3+, CD8+ T cells, B cells, monocytes, macrophages, T helper 1 (Th1), Th2, Th17 cells was reversed. CONCLUSION: NPY may be a biomarker for lupus, which may promote occurrence and development of lupus.


Subject(s)
Lupus Erythematosus, Systemic , Neuropeptide Y , Humans , Animals , Mice , Neuropeptide Y/genetics , Matrix Metalloproteinase 1 , CD8-Positive T-Lymphocytes , Matrix Metalloproteinase 8 , Immunoglobulin G
5.
Sci Rep ; 13(1): 15970, 2023 09 25.
Article in English | MEDLINE | ID: mdl-37749230

ABSTRACT

Systemic lupus erythematosus (SLE) is a chronic rheumatic disorder. Endothelin-1, a vasoconstrictor, belongs to the endothelin family and is associated with vascular-related damages. To date, association between ET-1 and pathogenesis of SLE remains unclear. This case-control study was carried out by 314 SLE, 252 non-SLE diseases patients and 500 healthy controls. Serum ET-1, CCN3, IL-28B levels were detected by ELISA, and ET-1 gene polymorphisms (rs5369, rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs4145451, rs6458155, rs9369217) were genotyped with Kompetitive Allele-Specific PCR. SLE patients had high levels of ET-1, which were correlated with some clinical, laboratory features. Serum CCN3, IL-28B levels were higher in SLE patients, and ET-1 levels were positively correlated with the two cytokines. Rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs6458155 and rs2070699 were associated with SLE risk. Rs2070699 (T, TT) was related to SLE patients with alopecia. Rs5370 (T, TT, TG), rs1476046 (G,GA), rs2071942 (G,GA) and rs2071943 (G,GA) were associated with SLE patients with pericarditis, pyuria and fever manifestation, respectively. Rs3087459 (CC) and rs9369217 (TC) were related to SLE patients with positive anti-SSB antibody. Rs5369 (AA) was associated with IgG and CRP levels in SLE patients. In conclusion, elevated serum ET-1 in SLE patients may be a potential disease marker, and its gene polymorphisms were related to SLE susceptibility.


Subject(s)
Endothelin-1 , Lupus Erythematosus, Systemic , Pericarditis , Humans , Case-Control Studies , Endothelin-1/genetics , Lupus Erythematosus, Systemic/genetics
6.
Inflamm Res ; 72(9): 1909-1918, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37725103

ABSTRACT

OBJECTIVE: Clinical evaluation of systemic lupus erythematosus (SLE) disease activity is limited and inconsistent, and high disease activity significantly, seriously impacts on SLE patients. This study aims to generate a machine learning model to identify SLE patients with high disease activity. METHOD: A total of 1014 SLE patients with low disease activity and 453 SLE patients with high disease activity were included. A total of 94 clinical, laboratory data and 17 meteorological indicators were collected. After data preprocessing, we use mutual information and multisurf to evaluate and select the importance of features. The selected features are used for machine learning modeling. Performance of the model is evaluated and verified by a series of binary classification indicators. RESULTS: We screened out hematuria, proteinuria, pyuria, low complement, precipitation, sunlight and other features for model construction by integrated feature selection. After hyperparameter optimization, the LGB has the best performance (ROC: AUC = 0.930; PRC: AUC = 0.911, APS = 0.913; balance accuracy: 0.856), and the worst is the naive bayes (ROC: AUC = 0.849; PRC: AUC = 0.719, APS = 0.714; balance accuracy: 0.705). Finally, the selection of features has good consistency in the composite feature importance bar plot. CONCLUSION: We identify SLE patients with high disease activity by a simple machine learning pipeline, especially the LGB model based on the characteristics of proteinuria, hematuria, pyuria and other feathers screened out by collective feature selection.


Subject(s)
Lupus Erythematosus, Systemic , Pyuria , Humans , Hematuria , Bayes Theorem , Lupus Erythematosus, Systemic/diagnosis , Machine Learning , Proteinuria
7.
Int J Rheum Dis ; 26(10): 2047-2054, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37578132

ABSTRACT

OBJECTIVES: To investigate whether machine learning, which is widely used in disease prediction and diagnosis based on demographic data and serological markers, can predict herpes occurrence in patients with systemic lupus erythematosus (SLE). METHODS: A total of 286 SLE patients were included in this study, including 200 SLE patients without herpes and 86 SLE patients with herpes. SLE patients were randomly divided into a training group and a test group, and 18 demographic characteristics and serological indicators were compared between the two groups. RESULTS: We selected basophil, monocyte, white blood cell, age, immunoglobulin E, SLE Disease Activity Index, complement 4, neutrophil, and immunoglobulin G as the basic features of modeling. A random forest model had the best performance, but logistic and decision tree analyses had better clinical decision-making benefits. Random forest had a good consistency between feature importance judgment and feature selection. The 10-fold cross-validation showed the optimization of five model parameters. CONCLUSION: The random forest model may be an excellently performing model, which may help clinicians to identify SLE patients whose disease is complicated by herpes early.

8.
Inflamm Res ; 72(6): 1315-1324, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37300586

ABSTRACT

OBJECTIVE: Diagnosis of lupus nephritis (LN) is a complex process, which usually requires renal biopsy. We aim to establish a machine learning pipeline to help diagnosis of LN. METHODS: A cohort of 681 systemic lupus erythematosus (SLE) patients without LN and 786 SLE patients with LN was established, and a total of 95 clinical, laboratory data and 17 meteorological indicators were collected. After tenfold cross-validation, the patients were divided into training set and test set. The features selected by collective feature selection method of mutual information (MI) and multisurf were used to construct the models of logistic regression, decision tree, random forest, naive Bayes, support vector machine (SVM), light gradient boosting (LGB), extreme gradient boosting (XGB), and artificial neural network (ANN), the models were compared and verified in post-analysis. RESULTS: Collective feature selection method screens out antistreptolysin (ASO), retinol binding protein (RBP), lupus anticoagulant 1 (LA1), LA2, proteinuria and other features, and the hyperparameter optimized XGB (ROC: AUC = 0.995; PRC: AUC = 1.000, APS = 1.000; balance accuracy: 0.990) has the best performance, followed by LGB (ROC: AUC = 0.992; PRC: AUC = 0.997, APS = 0.977; balance accuracy: 0.957). The worst performance is naive Bayes model (ROC: AUC = 0.799; PRC: AUC = 0.822, APS = 0.823; balance accuracy: 0.693). In the composite feature importance bar plots, ASO, RF, Up/Ucr, and other features play important roles in LN. CONCLUSION: We developed and validated a new and simple machine learning pathway for diagnosis of LN, especially the XGB model based on ASO, LA1, LA2, proteinuria, and other features screened out by collective feature selection.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Lupus Nephritis/diagnosis , Bayes Theorem , Proteinuria , Machine Learning
9.
Microbiol Spectr ; 11(1): e0276422, 2023 02 14.
Article in English | MEDLINE | ID: mdl-36622153

ABSTRACT

The prevalence of superbugs, represented by methicillin-resistant Staphylococcus aureus (MRSA), has become a serious clinical and public safety concern with rising incidence in hospitals. Polyketides with diverse chemical structures harbor many antimicrobial activities, including those of rifampin and rapamycin against MRSA. Streptomyces sp. QHH-9511 was isolated from a niche habitat in the Qinghai-Tibet Plateau and used to produce antibacterial metabolites. Herein, an integrated approach combining genome mining and metabolic analysis were employed to decipher the chemical origin of the antibacterial components with pigmented properties in strain QHH-9511, a novel Streptomyces species from a lichen symbiont on the Qinghai-Tibet Plateau. Genomic phylogeny assembled at the chromosome level revealed its unique evolutionary state. Further genome mining uncovered 36 candidate gene clusters, most of which were uncharacterized. Meanwhile, based on liquid chromatography coupled to diode array detection mass spectrometry, a series of granaticins, BSMs, chromones, phaeochromycins, and related molecules were discovered by using the Global Natural Product Social molecular networking platform. Subsequently, several pigment compounds were isolated and identified by high-resolution mass spectrometry and/or nuclear magnetic resonance, among which the structure-activity relationships of seven aromatic polyketides showed that the fused lactone ring of the C-2 carboxyl group could increase antibacterial activity. Genetic experiments indicated that all seven aromatic polyketides are a series of metabolic shunts produced by a single type II polyketide synthase (PKS) cluster. Comparative genomic analysis of granaticin producers showed that the granaticin gene cluster is widely distributed. This study provides an efficient method to combine genome mining and metabolic profiling techniques to uncover bioactive metabolites derived from specific habitats, while deepening our understanding of aromatic polyketide biosynthesis. IMPORTANCE Undescribed microorganisms from special habitats are being screened for anti-superbug drug molecules. In a project to screen actinomycetes for anti-MRSA activity, we isolated a Streptomyces strain from Qinghai Lake lichens. The phylogeny based on the genome assembled at the chromosome level revealed this strain's unique evolutionary state. The chemical origins of the antibacterial components with pigment properties in strain QHH-9511 were determined using an integrated approach combining genome mining and metabolic analysis. Further genome mining uncovered 36 secondary metabolite gene clusters, the majority of which were previously unknown. A series of aromatic compounds were discovered using molecular network analysis, separation, and extraction. Genetic experiments revealed that all seven aromatic polyketides are a series of metabolic shunts produced by a single cluster of type II PKSs. This study describes a method for identifying novel Streptomyces from specific habitats by combining genome mining with metabolic profiling techniques.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Polyketides , Streptomyces , Streptomyces/genetics , Streptomyces/metabolism , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Tibet , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Polyketides/chemistry , Polyketides/metabolism , Genomics , Phylogeny
10.
Front Immunol ; 14: 1305590, 2023.
Article in English | MEDLINE | ID: mdl-38164134

ABSTRACT

Systemic lupus erythematosus (SLE) is an inflammatory disorder related to immunity dysfunction. The Th1 cell family including Th1 cells, transcription factor T-bet, and related cytokines IFNγ, TNFα, IL-2, IL-18, TGF-ß, and IL-12 have been widely discussed in autoimmunity, such as SLE. In this review, we will comprehensively discuss the expression profile of the Th1 cell family in both SLE patients and animal models and clarify how the family members are involved in lupus development. Interestingly, T-bet-related age-associated B cells (ABCs) and low-dose IL-2 treatment in lupus were emergently discussed as well. Collection of the evidence will better understand the roles of the Th1 cell family in lupus pathogenesis, especially targeting IL-2 in lupus.


Subject(s)
Cytokines , Lupus Erythematosus, Systemic , Animals , Humans , Cytokines/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Interleukin-2/metabolism , Th1 Cells
11.
Ying Yong Sheng Tai Xue Bao ; 33(9): 2493-2500, 2022 Sep.
Article in Chinese | MEDLINE | ID: mdl-36131666

ABSTRACT

Quantitative assessment of livability within a city facilitates the identification of urban problems and targeted improvements to the environment. Available studies are mostly limited to static analysis of a particular phase. It is difficult to reveal the dynamic development state of cities at the micro level. Taking Sino-Singapore Tianjin Eco-city as an example, we established an evaluation index system for the livability of the eco-city from five dimensions, including environmental health, transportation convenience, urban security, facility convenience, and economic prosperity. Multi-source data from 2016 to 2020, including the remote sensing images, points of interest, and planning data, combined with the entropy method and the TOPSIS method were used to dynamically monitor the livability of the eco-city in a long-term series. The results showed that during the study period, the livability levels of different areas in the eco-city had strong spatial and temporal variations. Spatially, with the southern part of the Sino-Singapore Eco-city Cooperation Zone as the core, the overall livability was characterized by a high center and a low edge. The convenience of facilities, traffic convenience, and economic prosperity were characterized by a high center and a low edge. Urban security and environmental health showed the characteristics of low center and high edge. From 2016 to 2020, the livability improvement rate of the eco-city had gradually accelerated, with the the most obvious improvement in the southern part of the China-Singapore Cooperation Zone.


Subject(s)
Transportation , China , Cities , Entropy
12.
Front Immunol ; 13: 1073971, 2022.
Article in English | MEDLINE | ID: mdl-36761171

ABSTRACT

Hypoxia-inducible factor-1α (HIF-1α) is a primary metabolic sensor, and is expressed in different immune cells, such as macrophage, dendritic cell, neutrophil, T cell, and non-immune cells, for instance, synovial fibroblast, and islet ß cell. HIF-1α signaling regulates cellular metabolism, triggering the release of inflammatory cytokines and inflammatory cells proliferation. It is known that microenvironment hypoxia, vascular proliferation, and impaired immunological balance are present in autoimmune diseases. To date, HIF-1α is recognized to be overexpressed in several inflammatory autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and function of HIF-1α is dysregulated in these diseases. In this review, we narrate the signaling pathway of HIF-1α and the possible immunopathological roles of HIF-1α in autoimmune diseases. The collected information will provide a theoretical basis for the familiarization and development of new clinical trials and treatment based on HIF-1α and inflammatory autoimmune disorders in the future.


Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , Lupus Erythematosus, Systemic , Humans , Cytokines , Hypoxia-Inducible Factor 1, alpha Subunit
13.
iScience ; 24(9): 102951, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34458700

ABSTRACT

Heat shock factor 1 (HSF1) and 2 (HSF2) play distinct but overlapping regulatory roles in maintaining cellular proteostasis or mediating cell differentiation and development. Upon activation, both HSFs trimerize and bind to heat shock elements (HSEs) present in the promoter region of target genes. Despite structural insights gained from recent studies, structures reflecting the physiological architecture of this transcriptional machinery remains to be determined. Here, we present co-crystal structures of human HSF1 and HSF2 trimers bound to DNA, which reveal a triangular arrangement of the three DNA-binding domains (DBDs) with protein-protein interactions largely mediated by the wing domain. Two structural properties, different flexibility of the wing domain and local DNA conformational changes induced by HSF binding, seem likely to contribute to the subtle differential specificity between HSF1 and HSF2. Besides, two more structures showing DBDs bound to "two-site" head-to-head HSEs were determined as additions to the published tail-to-tail dimer-binding structures.

14.
Nat Prod Bioprospect ; 11(3): 325-332, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33963522

ABSTRACT

Two new sterpurane sesquiterpenoids named sterpurol D (1) and sterpurol E (2), and one skeletally new sesquiterpene, cryptomaraone (3), bearing a 5,6-fused bicyclic ring system, along with five known ones, sterpurol A (4), sterpurol B (5), paneolilludinic Acid (6), murolane-2α, 9ß-diol-3-ene (7) and (-)-10,11-dihydroxyfarnesol (8) were isolated from an endolichenic fungus Cryptomarasmius aucubae. The structures of the new compounds were elucidated by analysis of NMR spectroscopic spectra and HRESIMS data. The absolute configurations of 1 and 2 were established by spectroscopic data analysis and comparison of specific optical rotation, as well as the biosynthetic consideration. Additionally, compounds 1, 2, 4-6, and 8 showed significant nitric oxide (NO) production inhibition in Lipopolysaccharide (LPS)-induced BV-2 microglial cells with the IC50 values ranging from 9.06 to 14.81 µM.

15.
J Nat Prod ; 83(5): 1592-1597, 2020 05 22.
Article in English | MEDLINE | ID: mdl-32342692

ABSTRACT

Phaeosphaeria fuckelii, an endophytic fungus associated with the herbal medicine Phlomis umbrosa, produced four new thiodiketopiperazine alkaloids, phaeosphaones A-D (1-4), featuring an unusual ß-(oxy)thiotryptophan motif, along with four known analogues, phaeosphaone E (5), chetoseminudin B (6), polanrazine B (7), and leptosin D (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. Compounds 4, 6, and 8 were found to display mushroom tyrosinase inhibitory activity with IC50 values of 33.2 ± 0.2, 31.7 ± 0.2, and 28.4 ± 0.2 µM, respectively, more potent than that of the positive control, kojic acid (IC50 = 40.4 ± 0.1 µM). A molecular-docking study disclosed the π-π stacking interaction between the indole moiety of 8 and the His243 residue of tyrosinase.


Subject(s)
Alkaloids/chemistry , Ascomycota/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Agaricales , Crystallography, X-Ray , Molecular Structure
16.
J Agric Food Chem ; 68(8): 2418-2425, 2020 Feb 26.
Article in English | MEDLINE | ID: mdl-32011876

ABSTRACT

Two biosynthetically related new metabolites, eucalyptacid A (1) and eucalactam B (2), along with six known compounds (3-8), eugenitol (3), cytosporone C (4), 4-hydroxyphenethyl alcohol (5), 1-(4-hydroxyphenyl)ethane-1,2-diol (6), N-(2-hydroxy-2-phenylethyl)acetamide (7), and phomopene (8), were isolated from the solid rice cultures of the endophytic fungus Diaporthe eucalyptorum KY-9 that had been isolated from Melia azedarach. Also, two further new derivatives (2a, 2b) were prepared from 2. The structures were elucidated by exhaustive analysis of NMR and ESIMS data and chemical methods such as Marfey's protocol. Compound 1 was identified as a rare polyketide fatty acid, (8E)-3,5,11-trihydroxy-2,10,12-trimethyltetradecenoic acid, and 2 was determined to be the first cyclic depsipeptide containing the same fatty acid unit as 1 and a Gly-Gly-Thr tripeptide chain. Its N-terminal end is N-acylated by an 11-hydroxy fatty acid with a branch alkyl chain of 14:1. The 11-hydroxyl group connects to the carboxylic group of the C-terminal amino acid to form a 22-membered lactone ring. A hypothetical biosynthetic pathway for the new polyketides is proposed. The isolated compounds were assayed for their inhibition against four plant pathogenic fungi, Alternaria solani, Botrytis cinerea, Fusarium solani, and Gibberella saubinettii. Compounds 1, 4, 6, and 7 exhibited antifungal activities against Alternaria solani, with minimal inhibitory concentration (MIC) values from 6.25 to 50 µM. Thus, strain KY-9 represents an untapped source for the development of biological control agents to prevent the infection of pathogenic fungus A. solani.


Subject(s)
Fungicides, Industrial/metabolism , Fungicides, Industrial/pharmacology , Melia azedarach/microbiology , Saccharomycetales/chemistry , Alternaria/drug effects , Alternaria/growth & development , Botrytis/drug effects , Botrytis/growth & development , Fungicides, Industrial/chemistry , Fungicides, Industrial/isolation & purification , Fusarium/drug effects , Fusarium/growth & development , Microbial Sensitivity Tests , Saccharomycetales/isolation & purification , Saccharomycetales/metabolism
17.
Sci Rep ; 10(1): 198, 2020 01 13.
Article in English | MEDLINE | ID: mdl-31932628

ABSTRACT

NOD-like receptors (NLRs) localize in the cytosol to recognize intracellular pathogen products and initialize the innate immune response. However, the ligands and ligand specificity of many NLRs remain unclear. One such NLR, NLRP6, plays an important role in maintaining intestinal homeostasis and protecting against various intestinal diseases such as colitis and intestinal tumorigenesis. Here, we show that the major component of the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS), binds NLRP6 directly and induces global conformational change and dimerization. Following stimulation by ATP, the NLRP6 homodimer can further assemble into a linear molecular platform, and ASC is recruited to form higher molecular structures, indicative of a step-by-step activation mechanism. Our study sheds light on the mystery of LPS-induced inflammasome initiation, reveals the architecture and structural basis of potential pre-inflammasome, and suggests a novel molecular assembly pattern for immune receptors.


Subject(s)
Adenosine Triphosphate/metabolism , Inflammasomes/metabolism , Inflammation/pathology , Intracellular Signaling Peptides and Proteins/chemistry , Intracellular Signaling Peptides and Proteins/metabolism , Lipopolysaccharides/toxicity , CARD Signaling Adaptor Proteins/genetics , CARD Signaling Adaptor Proteins/metabolism , Homeostasis , Humans , Immunity, Innate , Inflammasomes/drug effects , Inflammation/chemically induced , Inflammation/immunology , Inflammation/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Protein Multimerization , Signal Transduction
18.
J Biol Chem ; 295(3): 808-821, 2020 01 17.
Article in English | MEDLINE | ID: mdl-31836667

ABSTRACT

The motile-sessile transition is critical for bacterial survival and growth. Cyclic-di-GMP (c-di-GMP) plays a central role in controlling this transition and regulating biofilm formation via various effectors. As an effector of c-di-GMP in Escherichia coli and related species, the PilZ domain-containing protein YcgR responds to elevated c-di-GMP concentrations and acts on the flagellar motor to suppress bacterial motility in a brakelike fashion, which promotes bacterial surface attachment. To date, several target proteins within the motor, MotA, FliG, and FliM, along with different regulatory mechanisms have been reported. However, how YcgR acts on these components remains unclear. Here, we report that activated YcgR stably binds to MotA at the MotA-FliG interface and thereby regulates bacterial swimming. Biochemical and structural analyses revealed that c-di-GMP rearranges the PilZ domain configuration, resulting in the formation of a MotA-binding patch consisting of an RXXXR motif and the C-tail helix α3. Moreover, we noted that a conserved region in the YcgR-N domain, which is independent of MotA interaction, is necessary for motility regulation. On the basis of these findings, we infer that the YcgR-N domain is required for activity on other motor proteins. We propose that activated YcgR appends to MotA via its PilZ domain and thereby interrupts the MotA-FliG interaction and simultaneously interacts with other motor proteins via its YcgR-N domain to inhibit flagellar motility. Our findings suggest that the mode of interaction between YcgR and motor proteins may be shared by other PilZ family proteins.


Subject(s)
Bacterial Proteins/chemistry , Escherichia coli Proteins/chemistry , Escherichia coli/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/ultrastructure , Escherichia coli/genetics , Escherichia coli/ultrastructure , Escherichia coli Proteins/genetics , Escherichia coli Proteins/ultrastructure , Flagella/chemistry , Flagella/genetics , Flagella/ultrastructure , Gene Expression Regulation, Bacterial , Guanosine Monophosphate/chemistry , Protein Binding/genetics
19.
Int J Mol Sci ; 20(24)2019 Dec 12.
Article in English | MEDLINE | ID: mdl-31842360

ABSTRACT

Drought stress is a major obstacle to agriculture. Although many studies have reported on plant drought tolerance achieved via genetic modification, application of plant growth-promoting rhizobacteria (PGPR) to achieve tolerance has rarely been studied. In this study, the ability of three isolates, including Bacillus amyloliquefaciens 54, from 30 potential PGPR to induce drought tolerance in tomato plants was examined via greenhouse screening. The results indicated that B. amyloliquefaciens 54 significantly enhanced drought tolerance by increasing survival rate, relative water content and root vigor. Coordinated changes were also observed in cellular defense responses, including decreased concentration of malondialdehyde and elevated concentration of antioxidant enzyme activities. Moreover, expression levels of stress-responsive genes, such as lea, tdi65, and ltpg2, increased in B. amyloliquefaciens 54-treated plants. In addition, B. amyloliquefaciens 54 induced stomatal closure through an abscisic acid-regulated pathway. Furthermore, we constructed biofilm formation mutants and determined the role of biofilm formation in B. amyloliquefaciens 54-induced drought tolerance. The results showed that biofilm-forming ability was positively correlated with plant root colonization. Moreover, plants inoculated with hyper-robust biofilm (ΔabrB and ΔywcC) mutants were better able to resist drought stress, while defective biofilm (ΔepsA-O and ΔtasA) mutants were more vulnerable to drought stress. Taken altogether, these results suggest that biofilm formation is crucial to B. amyloliquefaciens 54 root colonization and drought tolerance in tomato plants.


Subject(s)
Adaptation, Biological , Bacillus amyloliquefaciens/physiology , Biofilms , Droughts , Solanum lycopersicum/microbiology , Solanum lycopersicum/physiology , Stress, Physiological , Antioxidants/metabolism , Plant Development , Plant Roots/microbiology , Plant Roots/physiology , Symbiosis
20.
Front Microbiol ; 10: 1668, 2019.
Article in English | MEDLINE | ID: mdl-31396185

ABSTRACT

Beneficial microorganisms have been extensively used to make plants more resistant to abiotic and biotic stress. We previously identified a consortium of three plant growth-promoting rhizobacteria (PGPR) strains (Bacillus cereus AR156, Bacillus subtilis SM21, and Serratia sp. XY21; hereafter "BBS") as a promising and environmentally friendly biocontrol agent. In this study, the effect of BBS on a soil-borne disease of sweet pepper was evaluated. Application of BBS significantly reduced the prevalence of phytophthora blight and improved fruit quality and soil properties relative to the control. BBS was able to alter the soil bacterial community: it significantly increased the abundances of Burkholderia, Comamonas, and Ramlibacter, which were negatively associated with disease severity, relative to the control. A redundancy analysis suggested that BBS-treated soil samples were dominated by Burkholderia, Comamonas, Ramlibacter, Sporichthya, Achromobacter, and Pontibacter; abundance of these genera was related to total organic carbon (TOC), total nitrogen (TN), ammonium nitrogen (AN), total potassium (TP), and available phosphorus (AP) contents. This suggests that BBS treatment shifted the microbe community to one that suppressed soil-borne disease and improved the soil chemical properties.

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