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1.
Microb Pathog ; 195: 106909, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39218373

ABSTRACT

Brucellosis is a zoonotic disease caused by Brucella, which is difficult to eliminate by conventional drugs. Therefore, a novel multi-epitope vaccine (MEV) was designed to prevent human Brucella infection. Based on the method of "reverse vaccinology", cytotoxic T lymphocyte epitopes (CTLEs), helper T lymphocyte epitopes (HTLEs), linear B-cell epitopes (LBEs) and conformational B-cell epitopes (CBEs) of four Brucella proteins (VirB9, VirB10, Omp 19 and Omp 25) were obtained. In order to keep the correct protein folding, the multiple epitopes was constructed by connecting epitopes through linkers. In view of the significant connection between human leukocyte antigen CTLA-4 and B7 molecules found on antigen presenting cells (APCs), a new vaccine (V_C4MEV) for preventing brucellosis was created by combining CTLA-4 immunoglobulin variable region (IgV_CTLA-4) with MEV protein. Immunoinformatics analysis showed that V_C4MEV has a good secondary and tertiary structure. Additionally, molecular docking and molecular dynamics simulation (MD) revealed a robust binding affinity between IgV_ CTLA-4 and the B7 molecule. Notably, the vaccine V_C4MEV was demonstrated favorable immunogenicity and antigenicity in both in vitro and in vivo experiments. V_C4MEV had the potential to activate defensive cells and immune responses, offering a hopeful approach for developing vaccines against Brucella in the upcoming years.

2.
PLoS One ; 19(9): e0307877, 2024.
Article in English | MEDLINE | ID: mdl-39240891

ABSTRACT

Tuberculosis(TB) of the Central nervous system (CNS) is a rare and highly destructive disease. The emergence of drug resistance has increased treatment difficulty, leaving the Bacillus Calmette-Guérin (BCG) vaccine as the only licensed preventative immunization available. This study focused on identifying the epitopes of PknD (Rv0931c) and Rv0986 from Mycobacterium tuberculosis(Mtb) strain H37Rv using an in silico method. The goal was to develop a therapeutic mRNA vaccine for preventing CNS TB. The vaccine was designed to be non-allergenic, non-toxic, and highly antigenic. Codon optimization was performed to ensure effective translation in the human host. Additionally, the secondary and tertiary structures of the vaccine were predicted, and molecular docking with TLR-4 was carried out. A molecular dynamics simulation confirmed the stability of the complex. The results indicate that the vaccine structure shows effectiveness. Overall, the constructed vaccine exhibits ideal physicochemical properties, immune response, and stability, laying a theoretical foundation for future laboratory experiments.


Subject(s)
Computer Simulation , Molecular Docking Simulation , Molecular Dynamics Simulation , Mycobacterium tuberculosis , Tuberculosis, Central Nervous System , Humans , Mycobacterium tuberculosis/immunology , Tuberculosis, Central Nervous System/prevention & control , Tuberculosis, Central Nervous System/immunology , Tuberculosis Vaccines/immunology , Epitopes/immunology , Epitopes/chemistry , mRNA Vaccines , Vaccines, Synthetic/immunology
3.
Heliyon ; 10(14): e34721, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39148966

ABSTRACT

Brucellosis, a zoonotic disease caused by Brucella, presents a significant threat to both animal and human health. In animals, the disease can lead to infertility, miscarriage, and high fever, while in humans, symptoms may include recurrent fever, fatigue, sweating, hepatosplenomegaly, and joint and muscle pain following infection. Treatment often involves long-term antibiotic therapy, placing a substantial psychological and financial burden on patients. While vaccination is crucial for prevention, current animal vaccines have drawbacks such as residual virulence, and a safe and effective human vaccine is lacking. Hence, the development of a vaccine for brucellosis is imperative. In this study, we utilized bioinformatics methods to design a multi-epitope vaccine targeting Brucella. Targeting Heme transporter BhuA and polysaccharide export protein, we identified antigenic epitopes, including six cytotoxic T lymphocyte (CTL) dominant epitopes, six helper T lymphocyte (HTL) dominant epitopes, one conformation B cell dominant epitope, and three linear B cell dominant epitopes. By linking these epitopes with appropriate linkers and incorporating a Toll-like receptor (TLR) agonist (human beta-defensin-2) and an auxiliary peptide (Pan HLA-DR epitopes), we constructed the multi-epitope vaccine (MEV). The MEV demonstrated high antigenicity, non-toxicity, non-allergenicity, non-human homology, stability, and solubility. Molecular docking analysis and molecular dynamics simulations confirmed the interaction and stability of the MEV with receptors (MHCI, MHCII, TLR4). Codon optimization and in silico cloning validated the translation efficiency and successful expression of MEV in Escherichia coli. Immunological simulations further demonstrated the efficacy of MEV in inducing robust immune responses. In conclusion, our findings suggest that the engineered MEVs have the potential to stimulate both humoral and cellular immune responses, offering valuable insights for the future development of safe and efficient Brucella vaccines.

4.
Life Sci ; 355: 122986, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39151885

ABSTRACT

Brucellosis is a chronic infectious disease that is zoonotic in nature. Brucella can infect humans through interactions with livestock, primarily via the digestive tract, respiratory tract, and oral cavity. This bacterium has the potential to be utilized as a biological weapon and is classified as a Category B pathogen by the Centers for Disease Control and Prevention. Currently, there is no approved vaccine for humans against Brucella, highlighting an urgent need for the development of a vaccine to mitigate the risks posed by this pathogen. Brucella primarily infects its host by adhering to and penetrating mucosal surfaces. Mucosal immunity plays a vital role in preventing local infections, clearing microorganisms from mucosal surfaces, and inhibiting the spread of pathogens. As mucosal vaccine strategies continue to evolve, the development of a safe and effective mucosal vaccine against Brucella appears promising.This paper reviews the immune mechanism of mucosal vaccines, the infection mechanism of Brucella, successful Brucella mucosal vaccines in animals, and mucosal adjuvants. Additionally, it elucidates targeting and optimization strategies for mucosal vaccines to facilitate the development of human vaccines against Brucella.


Subject(s)
Brucella Vaccine , Brucella , Brucellosis , Immunity, Mucosal , Humans , Animals , Brucella/immunology , Immunity, Mucosal/immunology , Brucellosis/prevention & control , Brucellosis/immunology , Brucellosis/microbiology , Brucella Vaccine/immunology , Adjuvants, Immunologic , Vaccine Development
5.
Sci Total Environ ; 951: 175535, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39151636

ABSTRACT

Cascade reservoirs construction can greatly alter flow regime and sediment transport of rivers, further affecting migration and transformation processes of biogenic elements. The Jinsha River (JSR) is the China's largest hydropower base and the main runoff, sediment suspension, and nutrient source areas of the Yangtze River. However, the distribution, transport, and retention patterns of biogenic elements in the JSR are still unclear under the influence of cascade reservoirs. Therefore, monthly concentration monitoring work was conducted from November 2021 to October 2023 for various forms of carbon (C), nitrogen (N), phosphorus (P), and silicon (Si). Results showed that the concentrations and fluxes of total phosphorus (TP) and particulate phosphorus (PP) exhibited continuous decreasing trends along the reservoirs cascade, whereas N exhibited contrasting trends. The concentrations of dissolved total carbon (DTC), dissolved inorganic carbon (DIC), and total silicon also showed decreasing trends from upstream to downstream, whereas their fluxes were primarily influenced by runoff and exhibited upward fluctuations. Compared with other biogenic elements, there was a more pronounced retention effect on TP and PP by reservoirs, with average retention rates of 8.29 % and 16.01 %, respectively. Longer hydraulic retention time (HRT) can retain more TP and PP. Meanwhile, the retention rates of DTC, DIC, and particulate silicon were positively correlated with HRT, while the retention rate of dissolved silicon (DSi) showed a positive correlation with reservoir age. Moreover, the higher ratios of dissolved inorganic nitrogen to dissolved inorganic phosphorus (DIP) and DSi to DIP have occurred, resulting in apparent P limitation, particularly during the non-flood season due to lower DIP concentration. Overall, cascade reservoirs construction exists great influences on the spatial allocation, fluxes transport, and biogeochemical cycles of biogenic elements, potentially affecting the stability of rivers ecosystem along the food chain network.

6.
Sci Rep ; 14(1): 7278, 2024 03 27.
Article in English | MEDLINE | ID: mdl-38538674

ABSTRACT

Brucella, a gram-negative intracellular bacterium, causing Brucellosis, a zoonotic disease with a range of clinical manifestations, from asymptomatic to fever, fatigue, loss of appetite, joint and muscle pain, and back pain, severe patients have developed serious diseases affecting various organs. The mRNA vaccine is an innovative type of vaccine that is anticipated to supplant traditional vaccines. It is widely utilized for preventing viral infections and for tumor immunotherapy. However, research regarding its effectiveness in preventing bacterial infections is limited. In this study, we analyzed the epitopes of two proteins of brucella, the TonB-dependent outer membrane receptor BtuB and the LPS assembly protein LptD, which is involved in nutrient transport and LPS synthesis in Brucella. In order to effectively stimulate cellular and humoral immunity, we utilize a range of immunoinformatics tools such as VaxiJen, AllergenFPv.1.0 and SignalP 5.0 to design proteins. Finally, five cytotoxic T lymphocyte (CTL) cell epitopes, ten helper T lymphocyte (HTL) cell epitopes, and eight B cell epitopes were selected to construct the vaccine. Computer simulations are also used to verify the immune response of the vaccine. The codon optimization, in silico cloning showed that the vaccine can efficiently transcript and translate in E. coli. The secondary structure of mRNA vaccines and the secondary and tertiary structures of vaccine peptides were predicted and then docked with TLR-4. Finally, the stability of the developed vaccine was confirmed through molecular dynamics simulation. These analyses showed that the design the multi-epitope mRNA vaccine could potentially target extracellular protein of prevalent Brucella, which provided novel strategies for developing the vaccine.


Subject(s)
Brucella , Escherichia coli Proteins , Vaccines , Humans , Brucella/genetics , mRNA Vaccines , Escherichia coli , Lipopolysaccharides , Epitopes, T-Lymphocyte , Epitopes, B-Lymphocyte , T-Lymphocytes, Cytotoxic , Molecular Dynamics Simulation , Vaccines, Subunit , Computational Biology , Molecular Docking Simulation , Bacterial Outer Membrane Proteins/genetics
7.
Water Res ; 252: 121187, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38295452

ABSTRACT

Cascade reservoirs construction has modified the nutrients dynamics and biogeochemical cycles, consequently affecting the composition and productivity of river ecosystems. The Jinsha River, as the predominant contributor to runoff, suspended sediment (SS), and nutrients production within the Yangtze River, is a typical cascade reservoir region with unclear transport patterns and retention mechanisms of nutrients (nitrogen and phosphorus). Furthermore, how to regulate nutrients delivery in the cascade reservoirs region is also an urgent issue for basin water environment study. Therefore, we monitored monthly variations in nitrogen and phosphorus concentrations from November 2021 to October 2022 in the cascade reservoirs of the Jinsha River. The results indicated that the concentrations and fluxes of total phosphorus (TP) and particulate phosphorus (PP) decreased along the cascade of reservoirs, primarily due to PP deposited with SS, while opposing trends for total nitrogen (TN) and dissolved total nitrogen (DTN), which might be the consequences of human inputs and the increase of dissolved inorganic nitrogen discharged from the bottom of the reservoirs. Moreover, the positive average annual retention ratios for TP and PP were 10% and 16%, respectively, in contrast to the negative averages of -8 % for TN and -11% for particulate nitrogen (PN). The variability in runoff-sediment and hydraulic retention time (HRT) of cascade reservoirs played crucial roles in the retention of TP and PP. A regulatory threshold of HRT = 5.3 days in the flood season was obtained for controlling the balance of TP based on the stronger relationship between HRT and TP retention ratio. Consequently, the HRT of these reservoirs could be managed to control nutrients delivery, which was of particular significance for basin government institutions. This study enhances our comprehension of how cascade reservoirs influence the distribution and transport patterns of nutrients, offering a fresh perspective on nutrients delivery regulation.


Subject(s)
Water Pollutants, Chemical , Humans , Water Pollutants, Chemical/analysis , Environmental Monitoring , Ecosystem , Phosphorus/analysis , Nitrogen/analysis , Nutrients , China
8.
Microb Pathog ; 188: 106557, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38272330

ABSTRACT

The Notch signaling pathway is the most crucial link in the normal operation and maintenance of physiological functions of mammalian life processes. Notch receptors interact with ligands and this leads to three cleavages and goes on to enter the nucleus to initiate the transcription of target genes. The Notch signaling pathway deeply participates in the differentiation and function of various cells, including immune cells. Recent studies indicate that the outcomes of Notch signaling are changeable and highly dependent on different bacterial infection. The Notch signaling pathway plays a different role in promoting and inhibiting bacterial infection. In this review, we focus on the latest research findings of the Notch signaling pathway in bacterial infectious diseases. The Notch signaling pathway is critically involved in a variety of development processes of immunosuppression of different APCs. The Notch signaling pathway leads to functional changes in epithelial cells to aggravate tissue damage. Specifically, we illustrate the regulatory mechanism of the Notch signaling pathway in various bacterial infections, such as Mycobacterium tuberculosis, Mycobacterium avium paratuberculosis, Mycobacterium leprae, Helicobacter pylori, Klebsiella pneumoniae, Bacillus subtilis, Staphylococcus aureus, Ehrlichia chaffeensis and sepsis. Collectively, this review will not only help beginners intuitively and systematically understand the Notch signaling pathway in bacterial infectious diseases but also help experts to generate fresh insight in this field.


Subject(s)
Bacterial Infections , Communicable Diseases , Mycobacterium tuberculosis , Animals , Humans , Signal Transduction , Receptors, Notch/metabolism , Mycobacterium tuberculosis/metabolism , Mammals/metabolism
9.
Urol Oncol ; 42(3): 68.e1-68.e9, 2024 03.
Article in English | MEDLINE | ID: mdl-38097476

ABSTRACT

BACKGROUND: The impact of evolving treatment strategies for metastatic prostate cancer (mPCa) on real-world survival is not well understood. We analyzed changes in mPCa survival over the past decade and discussed the potential driving factors behind these changes. METHODS: Our study involved 43,228 mPCa patients (2004-2020) from the SEER database, divided into 4 diagnostic periods. We used a multivariate Cox proportional hazards model to evaluate diagnostic periods' influence on overall mortality (OM) and prostate cancer-specific mortality (PSM), and calculated relative median survival improvements between adjacent periods. Subgroup analyses based on age and distant metastasis sites were conducted. RESULTS: Patients diagnosed in 2016 to 2020 experienced significantly reduced mortality risk compared to those in 2004 to 2007 (HR 0.64 for OM, HR 0.62 for CSM, both P < 0.001). The study period witnessed an absolute improvement in median overall survival (OS) and prostate cancer-specific survival (PCSS), 17 months (54.8%) and 25 months (67.6%) respectively. The most rapid relative survival improvement occurred post-2016, with a 29.7% increase in median OS and a 37.8% increase in PCSS compared to 2012 to 2015. There was a significant reduction in mortality risk throughout the study period in both age groups (age <75 and ≥75), but absolute survival gains were smaller in the older group (24 months [68.6%] vs. 8 months [32%] for OS, 36 months [90.0%] vs. 11 months [33.3%] for PCSS), with lower relative survival improvements after 2016 (37.2% vs. 17.9% for OS, 49% vs. 22.2% for PCSS). All metastasis site subgroups (except M1a) exhibited a significant reduction in mortality risk (all P < 0.001). Absolute survival improvements were 58 months (134.9%) for M1a, 16 months (50.0%) for M1b, and 17 months (54.8%) for M1c. CONCLUSION: The survival of mPCa have significantly improved over the past decade, although the progress is slower in elderly patients. Investigating the underlying reasons for survival differences among various patient profiles can further refine mPCa treatment strategies.


Subject(s)
Adenocarcinoma , Prostatic Neoplasms , Male , Humans , Aged , Prostatic Neoplasms/pathology , Prostate/pathology , Adenocarcinoma/secondary , SEER Program
10.
PLoS One ; 18(8): e0286358, 2023.
Article in English | MEDLINE | ID: mdl-37561685

ABSTRACT

Brucellosis is a common zoonosis, which is caused by Brucella infection, and Brucella often infects livestock, leading to abortion and infertility. At present, human brucellosis remains one of the major public health problems in China. According to previous research, most areas in northwest China, including Xinjiang, Tibet, and other regions, are severely affected by Brucella. Although there are vaccines against animal Brucellosis, the effect is often poor. In addition, there is no corresponding vaccine for human Brucellosis infection. Therefore, a new strategy for early prevention and treatment of Brucella is needed. A multi-epitope vaccine should be developed. In this study, we identified the antigenic epitopes of the Brucella type IV secretion system VirB8 and Virb10 using an immunoinformatics approach, and screened out 2 cytotoxic T lymphocyte (CTL) epitopes, 9 helper T lymphocyte (HTL) epitopes, 6 linear B cell epitopes, and 6 conformational B cell epitopes. These advantageous epitopes are spliced together through different linkers to construct a multi-epitope vaccine. The silico tests showed that the multi-epitope vaccine was non-allergenic and had a strong interaction with TLR4 molecular docking. In immune simulation results, the vaccine construct may be useful in helping brucellosis patients to initiate cellular and humoral immunity. Overall, our findings indicated that the multi-epitope vaccine construct has a high-quality structure and suitable characteristics, which may provide a theoretical basis for the development of a Brucella vaccine.


Subject(s)
Brucella , Brucellosis , Vaccines , Animals , Humans , Type IV Secretion Systems , Epitopes, B-Lymphocyte , Molecular Docking Simulation , Epitopes, T-Lymphocyte , Brucellosis/prevention & control , Computational Biology/methods , Vaccines, Subunit
11.
J Biomol Struct Dyn ; : 1-19, 2023 Jul 09.
Article in English | MEDLINE | ID: mdl-37424209

ABSTRACT

Chronic infection induced by immune tolerance to hepatitis B virus (HBV) is one of the most common causes of hepatic cirrhosis and hepatoma. Fortunately, the application of therapeutic vaccine can not only reverse HBV-tolerance, but also serve a potentially effective therapeutic strategy for treating chronic hepatitis B (CHB). However, the clinical effect of the currently developed CHB therapeutic vaccine is not optimistic due to the weak immunogenicity. Given that the human leukocyte antigen CTLA-4 owns strong binding ability to the surface B7 molecules (CD80 and CD86) of antigen presenting cell (APCs), the immunoglobulin variable region of CTLA-4 (IgV_CTLA-4) was fused with the L protein of HBV to contrive a novel therapeutic vaccine (V_C4HBL) for CHB in this study. We found that the addition of IgV_CTLA-4 did not interfere with the formation of L protein T cell and B cell epitopes after analysis by means of immunoinformatics approaches. Meanwhile, we also found that the IgV_CTLA-4 had strong binding force to B7 molecules through molecular docking and molecular dynamics (MD) simulation. Notably, our vaccine V_C4HBL showed good immunogenicity and antigenicity by in vitro and in vivo experiments. Therefore, the V_C4HBL is promising to again effectively activate the cellular and humoral immunity of CHB patients, and provides a potentially effective therapeutic strategy for the treatment of CHB in the future.Communicated by Ramaswamy H. Sarma.

12.
BMC Pulm Med ; 23(1): 163, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37173731

ABSTRACT

BACKGROUND: The study investigated the effects and underlying mechanisms of intestinal flora metabolite butyrate on inflammatory ILC2 cells (iILC2s)-mediated lung inflammation in chronic obstructive pulmonary disease (COPD). METHODS: Mouse models of COPD and acute exacerbation of COPD (AECOPD) were established. Flow cytometry was used to detect natural ILC2 cells (nILC2s) and iILC2s in lung and colon tissues. The 16s rRNA and GC-MS were used to detect microbial flora and short chain fatty acids (SCFAs) in feces. ELISA was used to detect IL-13 and IL-4. Western blot and qRT-PCR were used to detect the relative protein and mRNA levels, respectively. In vitro experiments were performed with sorted ILC2s from colon tissues of control mice. Mice with AECOPD were treated with butyrate. RESULTS: The nILC2s and iILC2s in lung and colon tissues of AECOPD mice were significantly higher than control groups. The abundance of the flora Clostridiaceae was significantly reduced, and the content of SCFAs, including acetate and butyrate, was significantly reduced. The in vitro experiments showed that butyrate inhibited iILC2 cell phenotype and cytokine secretion. Butyrate treatment reduced the proportion of iILC2 cells in the colon and lung tissues of mice with AECOPD. CONCLUSIONS: The nILC2s and iILC2s in the colon tissues are involved in the course of COPD. Decreased Clostridiaceae and butyrate in AECOPD mice caused the accumulation of iILC2 cells in the intestines and lungs. Supplementation of butyrate can reduce iILC2 in the intestine and lung tissues. Our data may provide new ideas for prevention and treatment of COPD.


Subject(s)
Pneumonia , Pulmonary Disease, Chronic Obstructive , Animals , Mice , Immunity, Innate , Butyrates/pharmacology , RNA, Ribosomal, 16S , Lymphocytes , Lung , Pneumonia/drug therapy
13.
Front Immunol ; 14: 1137195, 2023.
Article in English | MEDLINE | ID: mdl-37056763

ABSTRACT

Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be divided into stable phase and acute exacerbation phase (AECOPD) and is characterized by inflammation and hyper-immunity. Methylation of N6-methyladenosine (m6A) is an epigenetic modification that regulates the expression and functions of genes by influencing post-transcriptional RNA modifications. Its influence on the immune regulation mechanism has attracted great attention. Herein, we present the m6Amethylomic landscape and observe how the methylation of m6A participates in the pathological process of COPD. The m6A modification of 430 genes increased and that of 3995 genes decreased in the lung tissues of mice with stable COPD. The lung tissues of mice with AECOPD exhibited 740 genes with hypermethylated m6A peak and 1373 genes with low m6A peak. These differentially methylated genes participated in signaling pathways related to immune functions. To further clarify the expression levels of differentially methylated genes, RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing data were jointly analyzed. In the stable COPD group, 119 hypermethylated mRNAs (82 upregulated and 37 downregulated mRNAs) and 867 hypomethylated mRNAs (419 upregulated and 448 downregulated mRNAs) were differentially expressed. In the AECOPD group, 87 hypermethylated mRNAs (71 upregulated and 16 downregulated mRNAs) and 358 hypomethylated mRNAs (115 upregulated and 243 downregulated mRNAs) showed differential expression. Many mRNAs were related to immune function and inflammation. Together, this study provides important evidence on the role of RNA methylation of m6A in COPD.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Animals , Mice , Pulmonary Disease, Chronic Obstructive/genetics , RNA , RNA, Messenger/genetics , Adenosine , Inflammation , Lung
14.
BMC Cardiovasc Disord ; 22(1): 494, 2022 11 20.
Article in English | MEDLINE | ID: mdl-36404328

ABSTRACT

BACKGROUND: In patients with heart failure, anxiety disorder is common and associated with adverse prognosis. This study intended to find more confounding factors of Chinese heart failure patients. METHODS: We enrolled 284 hospitalized heart failure patients, whose New York Heart Association (NYHA) classed as II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. All the patients were scaled in Hamilton Rating Scale for Anxiety (14-items) (HAM-A14). Ordinal logistic regression analysis was performed to examine the association of correlated factors with anxiety disorder. RESULTS: There were 184 patients had anxiety accounting for 64.8% of all 284 hospitalized heart failure patients. The neutrophilic granulocyte percentage, urea nitrogen, total bilirubin and brain natriuretic peptide were positively associated with HAM-A14 score, meanwhile, the hemoglobin, red blood cells counts, albumin and LVEF were negatively associated with HAM-A14 score (All P < 0.05). After the adjustments of sex, hemoglobin, urea nitrogen, total bilirubin, albumin and brain natriuretic peptide, the neutrophilic granulocyte percentage was significantly associated with anxiety (OR = 43.265, P = 0.012). The neutrophilic granulocyte percentage was 0.616 ± 0.111, 0.640 ± 0.102, 0.681 ± 0.106 and 0.683 ± 0.113 in heart failure patients with no anxiety, possible anxiety, confirmed anxiety and obvious anxiety, respectively. CONCLUSIONS: Neutrophilic granulocyte percentage as well as the traditional risk factors such as sex, urea nitrogen and brain natriuretic peptide is associated with anxiety in hospitalized heart failure patients.


Subject(s)
Heart Failure , Natriuretic Peptide, Brain , Humans , Stroke Volume , Ventricular Function, Left , Heart Failure/diagnosis , Anxiety Disorders , Granulocytes/chemistry , Bilirubin , Albumins/analysis , Nitrogen/analysis , China/epidemiology , Urea
15.
Mol Biol Rep ; 49(8): 7497-7506, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35715604

ABSTRACT

BACKGROUND: Tim-3/Galectin-9 is involved in the immune escape of many pathogens. However, the role of Tim-3/Galectin-9 in persistent infection of Echinococcus multilocularis (Em), which is related to immune escape, is still unclear. OBJECTIVE: To investigate the role of Tim-3/Galectin-9 and related cytokines in mice with persistent infection of Em. METHODS: Em infection model was established by injecting the protoscoleces. Serum was collected at days 2, 8, 30, 60, 90, 180 and 270 after infection. Lymphocytes were isolated from liver tissue samples with Ficoll. Tim-3 + CD4 + T percentage was analyzed by flow cytometry. CD4 + T cells were isolated from liver tissues of Em infected mice and cultured in vitro. The mRNA levels of Tim-3, Galectin-9, IFN-γ and IL-4 were detected by qRT-PCR. Cytokine levels in serum and culture supernatant (IFN-γ and IL-4) were analyzed by cytometric bead array. RESULTS: The expression of Tim-3 and Galectin-9 mRNA significantly increased after 30 days of infection, reached peak on day 90, and then decreased slightly on days 180-270. The expression of IFN-γ mRNA, increased on day 2 and 8 after infection, slightly decreased on days 30-60, and obvious decreased on days 90-270, but were still higher than those of the control group. The expression of IL-4 mRNA gradually increased along with the time of infection. In serum of Em infected mice, level of IFN-γ peaked at day 30 and then gradually decreased; whereas IL-4 level peaked at day 90 and then gradually decreased. In vitro experiment found that Tim-3/Galectin-9 directly caused the changes in the levels of IFN-γ and IL-4. CONCLUSIONS: Tim-3/Galectin-9 signaling pathway may be involved in the development of persistent infection of Em by regulating the production of Th1 and Th2 cytokines.


Subject(s)
Cytokines , Hepatitis A Virus Cellular Receptor 2 , Animals , Echinococcosis , Galectins/genetics , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/metabolism , Interleukin-4/genetics , Mice , RNA, Messenger/metabolism , Signal Transduction
16.
Sci Rep ; 12(1): 10146, 2022 06 16.
Article in English | MEDLINE | ID: mdl-35710873

ABSTRACT

Brucella is a typical facultative intracellular bacterium that can cause zoonotic infections. For Brucella, it is difficult to eliminate with current medical treatment. Therefore, a multi-epitope vaccine (MEV) should be designed to prevent Brucella infection. For this purpose, we applied the reverse vaccinology approach from Omp10, Omp25, Omp31 and BtpB. Finally, we obtained 13 cytotoxic T lymphocyte (CTL) epitopes, 17 helper T lymphocyte (HTL) epitopes, 9 linear B cell epitopes, and 2 conformational B cell epitopes for further study. To keep the protein folded normally, we linked AAY, GPGPG, and KK to CTL epitopes, HTL epitopes, and B cell epitopes, respectively. The N-terminal of the vaccine peptide is supplemented with appropriate adjuvants to enhance immunogenicity. To evaluate its immunogenicity, stability, safety, and feasibility, a final MEV containing 806 amino acids was constructed by linking linkers and adjuvants. In addition, molecular docking and molecular dynamics simulations were performed to verify the affinity and stability of the MEV-TLR4. Then, codon adaptation and in silico cloning studies were carried out to identify the possible codons for expressing the MEV. In animal experiments, the results demonstrated that the MEV had high immunogenicity. Collectively, this study provided a theoretical basis for the development of a Brucella vaccine.


Subject(s)
Brucella melitensis , Animals , Computational Biology/methods , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Molecular Docking Simulation , Vaccines, Subunit
17.
Front Immunol ; 13: 884433, 2022.
Article in English | MEDLINE | ID: mdl-35603198

ABSTRACT

The development of an effective multivalent vaccine against SARS-CoV-2 variants is an important means to improve the global public health situation caused by COVID-19. In this study, we identified the antigen epitopes of the main global epidemic SARS-CoV-2 and mutated virus strains using immunoinformatics approach, and screened out 8 cytotoxic T lymphocyte epitopes (CTLEs), 17 helper T lymphocyte epitopes (HTLEs), 9 linear B-cell epitopes (LBEs) and 4 conformational B-cell epitopes (CBEs). The global population coverage of CTLEs and HTLEs was 93.16% and 99.9% respectively. These epitopes were spliced together by corresponding linkers and recombined into multivalent vaccine. In silico tests, the vaccine protein was a non-allergen and the docking with TLR-3 molecule showed a strong interaction. The results of immune simulation showed that the vaccine may be helpful to initiate both cellular and humoral immunity against all VOC. The optimistic immunogenicity of the vaccine was confirmed in vivo and in vitro finally. Therefore, our vaccine may have potential protection against SARS-CoV-2 and its variants.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines , Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/genetics , Humans , Molecular Docking Simulation , SARS-CoV-2/genetics , Vaccines, Combined
18.
Transl Androl Urol ; 11(2): 202-212, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35280667

ABSTRACT

Background: Androgen receptor variant 7 (AR-V7) detection provides important information for the clinical management of abiraterone in metastatic castration-resistant prostate cancer (mCRPC). We performed a non-invasive urine-derived exosomal AR-V7 analysis of mCRPC patients. Methods: A total of 34 mCRPC patients were recruited including 16 patients treated with abiraterone (ABI) with stable prostate-specific antigen (PSA)/radiograph response (the ABI-Sta group) and 18 were resistant to abiraterone (the ABI-Res group). Urine was collected from patients and healthy control patients for the analysis. Exosomal ribonucleic acid was isolated from urine. Urinary exosome-based androgen receptor-variant 7 was detected by quantitative real-time polymerase chain reaction assay. Characteristics of patients and survival data were collected. The correlation between AR-V7 expression and the therapeutic effect/survival outcomes of abiraterone was analyzed. Results: Urine is the ideal biological sample for exosome separation and AR full-length analysis. Positive urine-derived exosomal AR-V7 was detected in 32.4% (11 of 34) of the mCRPC patients' urine samples. Positive AR-V7 was more common in the ABI-Res patients than the ABI-Sta patients (50.0% vs. 12.5%, respectively; P=0.009), and was associated with a higher PSA progression rate and poorer overall survival (OS) (P=0.0031, and P=0.0012, respectively). Conclusions: The present study showed that the detection of urine-derived exosomal AR-V7 provides a sensitive and feasible clinical workflow. The predicting role of urine-derived exosomal AR-V7 in mCRPC patients should be further verified using studies with greater sample sizes.

19.
FASEB J ; 36(4): e22252, 2022 04.
Article in English | MEDLINE | ID: mdl-35294065

ABSTRACT

In view of the high infection rate of Helicobacter pylori, a safe and effective vaccine is urgently needed. Recent trends in vaccine design have shifted toward safe and specific epitope-based vaccines. In this study, by using different immunoinformatics approaches, a total of eight linear B cell epitopes, four HTL and three CTL epitopes of FlaA and UreB proteins of H. pylori G27 strain were screened out, we also predicted the conformational epitopes of the two proteins. Then, the dominant epitopes were sequentially linked by appropriate linkers, and the cytotoxic T lymphocyte-associated antigen 4 extracellular domain was attached to the N-terminal of the epitope sequence. Meanwhile, molecular docking, molecular dynamics simulations and principal component analysis were performed to show that the multi-epitope vaccine structure had strong interactions with B7 (B7-1, B7-2) and Toll-like receptors (TLR-2, -4). Eventually, the effectiveness of the vaccine was validated using in silico cloning. These analyses suggested that the designed vaccine could target antigen-presenting cells and had high potency against H. pylori, which could provide a reference for the future development of efficient H. pylori vaccines.


Subject(s)
Helicobacter pylori , Vaccines , CTLA-4 Antigen , Computational Biology , Epitopes, T-Lymphocyte , Molecular Docking Simulation
20.
Front Immunol ; 12: 668492, 2021.
Article in English | MEDLINE | ID: mdl-34456902

ABSTRACT

All the time, echinococcosis is a global zoonotic disease which seriously endangers public health all over the world. In order to speed up the development process of anti-Echinococcus granulosus vaccine, at the same time, it can also save economic cost. In this study, immunoinformatics tools and molecular docking methods were used to predict and screen the antigen epitopes of Echinococcus granulosus, to design a multi-epitope vaccine containing B- and T-cell epitopes. The multi-epitope vaccine could activate B lymphocytes to produce specific antibodies theoretically, which could protect the human body against Echinococcus granulosus infection. It also could activate T lymphocytes and clear the infected parasites in the body. In this study, four CD8+ T-cell epitopes, three CD4+ T-cell epitopes and four B-cell epitopes of Protein EgTeg were identified by immunoinformatics methods. Meanwhile, three CD8+ T-cell epitopes, two CD4+ T-cell epitopes and four B-cell epitopes of Protein EgFABP1 were identified. We constructed the multi-epitope vaccine using linker proteins. The study based on the traditional methods of antigen epitope prediction, further optimized the prediction results combined with molecular docking technology and improved the precision and accuracy of the results. Finally, in vivo and in vitro experiments had verified that the vaccine designed in this study had good antigenicity and immunogenicity.


Subject(s)
Antigens, Helminth/pharmacology , Drug Design , Echinococcosis/prevention & control , Echinococcus granulosus/immunology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Molecular Docking Simulation , Vaccines, DNA/pharmacology , Adolescent , Adult , Animals , Antibodies, Helminth/blood , Antigens, Helminth/immunology , B-Lymphocytes/immunology , B-Lymphocytes/parasitology , Cells, Cultured , Computer-Aided Design , Disease Models, Animal , Echinococcosis/blood , Echinococcosis/immunology , Echinococcosis/parasitology , Fatty Acid-Binding Proteins/immunology , Fatty Acid-Binding Proteins/pharmacology , Humans , Immunity, Humoral , Immunogenicity, Vaccine , Lymphocyte Activation , Mice, Inbred BALB C , Middle Aged , T-Lymphocytes/immunology , T-Lymphocytes/parasitology , Vaccines, DNA/immunology , Vaccines, Subunit/immunology , Vaccines, Subunit/pharmacology , Young Adult
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