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1.
Nat Commun ; 15(1): 3751, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704398

ABSTRACT

Association of circulating glycoprotein acetyls (GlycA), a systemic inflammation biomarker, with lung function and respiratory diseases remain to be investigated. We examined the genetic correlation, shared genetics, and potential causality of GlycA (N = 115,078) with lung function and respiratory diseases (N = 497,000). GlycA showed significant genetic correlation with FEV1 (rg = -0.14), FVC (rg = -0.18), asthma (rg = 0.21) and COPD (rg = 0.31). We consistently identified ten shared loci (including chr3p21.31 and chr8p23.1) at both SNP and gene level revealing potential shared biological mechanisms involving ubiquitination, immune response, Wnt/ß-catenin signaling, cell growth and differentiation in tissues or cells including blood, epithelium, fibroblast, fetal thymus, and fetal intestine. Genetically elevated GlycA was significantly correlated with lung function and asthma susceptibility (354.13 ml decrement of FEV1, 442.28 ml decrement of FVC, and 144% increased risk of asthma per SD increment of GlycA) from MR analyses. Our findings provide insights into biological mechanisms of GlycA in relating to lung function, asthma, and COPD.


Subject(s)
Asthma , Biomarkers , Lung , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive , Humans , Asthma/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Biomarkers/metabolism , Biomarkers/blood , Male , Female , Genetic Predisposition to Disease , Glycoproteins/genetics , Glycoproteins/metabolism , Middle Aged , Inflammation/genetics , Genome-Wide Association Study , Adult , Aged , Respiratory Function Tests , Forced Expiratory Volume
2.
Microbiol Spectr ; 11(6): e0105923, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37846986

ABSTRACT

IMPORTANCE: Our results suggest that rhizosphere bacteria are more sensitive to bacterial leaf blight (BLB) than fungi. BLB infection decreased the diversity of the rhizosphere bacterial community but increased the complexity and size of the rhizosphere microbial community co-occurrence networks. In addition, the relative abundance of the genera Streptomyces, Chitinophaga, Sphingomonas, and Bacillus increased significantly. Finally, these findings contribute to the understanding of plant-microbiome interactions by providing critical insight into the ecological mechanisms by which rhizosphere microbes respond to phyllosphere diseases. In addition, it also lays the foundation and provides data to support the use of plant microbes to promote plant health in sustainable agriculture, providing critical insight into ecological mechanisms.


Subject(s)
Microbiota , Oryza , Rhizosphere , Soil Microbiology , Bacteria
7.
J Control Release ; 350: 734-747, 2022 10.
Article in English | MEDLINE | ID: mdl-36063959

ABSTRACT

Mirroring the rapid clinical performance, immune checkpoint blockade (ICB) leads a remarkable clinical advance in combating cancer, but suffers poor response in most cancers. The low presence of tumor-infiltration lymphocytes and the poor immunogenicity in tumor microenvironment (TME) are the main factors hindering the effectiveness of ICB in the treatment of immunological "cold" tumors. Aiming at boosting immune response via TME modulation, we report a near-infrared laser-guided photoimmuno-strategy in which synergistic phototherapy, immune adjuvant, and ICB are integrated into one versatile nanoporphyrin platform. The prepared nanoporphyrins are self-assembled from purpurin18-lipids and have photodynamic/photothermal and immunomodulatory effects that can be tuned under a single laser irradiation, concomitant with fluorescence or MSOT imaging. In this work, the contributions of each component in the nanoporphyrin platform were specified. In particular, phototherapy-driven in situ tumor cell death provided abundant tumor-associated antigens to initiate immune responses. With the assist of spatiotemporally delivered immune adjuvant, phototherapy potentiated tumor immunogenicity, reprogrammed "cold" tumors into "hot" ones, and sensitized tumors to ICB therapy. Further combined with PD-L1 blockade, the photoimmune-strategy substantially stimulated tumor-specific immune-responses and long-term immunological memory against primary tumor, abscopal tumor as well as metastatic foci. Such single light-primed photoimmunotherapy offers a promising solution to overcome common hurdles in ICB treatment and can potentially be integrated into existing clinical practice.


Subject(s)
B7-H1 Antigen , Neoplasms , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Antigens, Neoplasm/therapeutic use , Etoposide/therapeutic use , Humans , Immune Checkpoint Inhibitors , Immunity , Immunotherapy/methods , Lipids/therapeutic use , Neoplasms/drug therapy , Phototherapy , Tumor Microenvironment
10.
Phytopathology ; 112(8): 1610-1619, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35240868

ABSTRACT

The type III secretion system (T3SS) is a key factor in the pathogenesis of Pseudomonas syringae pv. actinidiae biovar 3 (Psa3), the causal agent of a global kiwifruit bacterial canker pandemic. To monitor the T3SS expression levels in Psa3, we constructed a luciferase reporter plasmid-expressing HrpAPsa3-NLuc fusion protein. The expression of HrpA-NLuc was induced in hrp-inducing conditions whereas the level of luciferase activity correlated with the expression of hrp/hrc genes in Psa3 confirmed the reliability of the reporter construct. Based on the readout of the NLuc reporter construct, three small molecule compounds 4-methoxy-cinnamic acid, sulforaphane, and ferulic acid were determined as T3SS inhibitors in Psa3, whereas sodium acetate was determined to be a T3SS inducer. Moreover, the aqueous extract of fruit inhibited the accumulation of HrpA-NLuc in Psa3 in medium and in planta. Additionally, the T3SS inhibitors suppress Psa3 virulence, whereas the T3SS inducer promotes Psa3 virulence on kiwifruit. Thus, our findings may provide clues to why the fruit is not infected by Psa3, and the Psa3 T3SS inhibitors have potential as alternatives to current nonspecific antimicrobials for disease management.


Subject(s)
Actinidia , Pseudomonas syringae , Actinidia/microbiology , Luciferases/genetics , Plant Diseases/microbiology , Pseudomonas syringae/genetics , Reproducibility of Results , Type III Secretion Systems/genetics
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