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Journal of Experimental & Clinical... Oct 2023Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of...
BACKGROUND
Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of splicing factor 3b subunit 4 (SF3B4) as a novel non-invasive biomarker for HCC and determine the association between SF3B4 expression and immune cell infiltration.
METHODS
An enzyme-linked immunosorbent assay (ELISA) was used to detect SF3B4 levels in plasma samples obtained from healthy controls (HCs) and patients with chronic hepatitis, liver cirrhosis, and HCC. The expression levels of autoantibodies that detect SF3B4 in the plasma samples of each group of patients were measured. Small extracellular vesicles (EVs) were isolated from patient sera, and the expression levels of EV-SF3B4 were measured using quantitative reverse transcription PCR.
RESULTS
ELISA results confirmed that the expression levels of SF3B4 proteins and autoantibodies in the plasma of patients with HCC were higher than those in HCs. However, their diagnostic performance was not better than that of alpha-fetoprotein (AFP). The mRNA expression of SF3B4 in serum EV increased but not in the buffy coat or serum of patients with HCC. Serum EV-SF3B4 displayed better diagnostic power than AFP for all stages of HCC (AUC = 0.968 vs. 0.816), including early-stage HCC (AUC = 0.960 vs. 0.842), and this was consistent in the external cohort. Single-cell RNA sequencing indicated that SF3B4 expression was correlated with myeloid-derived suppressor cells. The Tumor Immune Estimation Resource database reconfirmed the correlation between SF3B4 expression and immune cell infiltration in HCC.
CONCLUSIONS
SF3B4 may be associated with tumor immune infiltration in HCC, and EV-SF3B4 shows potential as a novel non-invasive diagnostic biomarker of HCC.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Biomarkers, Tumor; RNA Splicing Factors; Extracellular Vesicles; Autoantibodies
PubMed: 37899451
DOI: 10.1186/s13046-023-02867-y -
Human Vaccines & Immunotherapeutics Dec 2023The receptor-binding domain (RBD) of SARS-CoV-2 S protein is proved to be the major target of neutralizing antibodies. However, on the S protein, only a portion of...
The receptor-binding domain (RBD) of SARS-CoV-2 S protein is proved to be the major target of neutralizing antibodies. However, on the S protein, only a portion of epitopes in RBD can be effectively displayed with dynamic changes in spatial conformations. Using RBD fragment as antigen can better expose the neutralizing epitopes, but the immunogenicity of RBD monomer is suboptimal. Multimeric display of RBD molecules is a feasible strategy to optimize RBD-based vaccines. In this study, RBD single-chain dimer derived from Wuhan-Hu-1 was fused with a trimerization motif, and a cysteine was also introduced at the C-terminus. The resultant recombinant protein 2RBDpLC was expressed in 9 cells using a baculovirus expression system. Reducing/non-reducing PAGE, size-exclusion chromatography and in silico structure prediction indicated that 2RBDpLC polymerized and possibly formed RBD dodecamers through trimerization motif and intermolecular disulfide bonds. In mice, 2RBDpLC induced higher levels of RBD-specific and neutralizing antibody responses than RBD dimer, RBD trimer and prefusion-stabilized S protein (S2P). In addition, cross-neutralizing antibodies against Delta and Omicron VOC were also detected in the immune sera. Our results demonstrate that 2RBDpLC is a promising vaccine candidate, and the method of constructing dodecamers may be an effective strategy for designing RBD-based vaccines.
Topics: Animals; Mice; Humans; SARS-CoV-2; COVID-19; Antibodies, Viral; Viral Vaccines; Antibodies, Neutralizing; Spike Glycoprotein, Coronavirus; Recombinant Proteins; Epitopes
PubMed: 36846890
DOI: 10.1080/21645515.2023.2174755 -
Frontiers in Immunology 2023The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity...
Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study.
INTRODUCTION
The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined.
METHODS
We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis.
RESULTS
The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies.
DISCUSSION
The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.
Topics: Humans; Antilymphocyte Serum; Peripheral Blood Stem Cell Transplantation; Follow-Up Studies; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Epstein-Barr Virus Infections; Peripheral Blood Stem Cells; Herpesvirus 4, Human; Cyclophosphamide; Graft vs Host Disease; Neoplasms
PubMed: 37954615
DOI: 10.3389/fimmu.2023.1252879 -
Emerging Microbes & Infections Dec 2023Since the first human case in 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1500 human infections with a mortality rate of approximately 40%. Despite...
Since the first human case in 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1500 human infections with a mortality rate of approximately 40%. Despite large-scale poultry vaccination regimes across China, the H7N9 AIVs continue to persist and evolve rapidly in poultry. Recently, several strains of H7N9 AIVs have been isolated and shown the ability to escape vaccine-induced immunity. To assess the zoonotic risk of the recent H7N9 AIV isolates, we rescued viruses with hemagglutinin (HA) and neuraminidase (NA) from these H7N9 AIVs and six internal segments from PR8 virus and characterized their receptor binding, pH of fusion, thermal stability, plaque morphology and virus replication. We also assessed the cross-reactivity of the viruses with human monoclonal antibodies (mAbs) against H7N9 HA and ferret antisera against H7N9 AIV candidate vaccines. The H7N9 AIVs from the early epidemic waves had dual sialic acid receptor binding characteristics, whereas the more recent H7N9 AIVs completely lost or retained only weak human sialic acid receptor binding. Compared with the H7N9 AIVs from the first epidemic wave, the 2020/21 viruses formed larger plaques in Madin-Darby canine kidney (MDCK) cells and replicated to higher titres , demonstrating increased acid stability but reduced thermal stability. Further analysis showed that these recent H7N9 AIVs had poor cross-reactivity with the human mAbs and ferret antisera, highlighting the need to update the vaccine candidates. To conclude, the newly emerged H7N9 AIVs showed characteristics of typical AIVs, posing reduced zoonotic risk but a heightened threat for poultry.
Topics: Animals; Dogs; Humans; Influenza A Virus, H7N9 Subtype; Ferrets; Hemagglutinins; Poultry; Risk Assessment; Immune Sera; Influenza, Human; Influenza in Birds; Hemagglutinin Glycoproteins, Influenza Virus
PubMed: 36714929
DOI: 10.1080/22221751.2023.2172965 -
BioRxiv : the Preprint Server For... Sep 2023The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an...
The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.
PubMed: 37808679
DOI: 10.1101/2023.09.27.559689 -
Brain and Behavior Dec 2023The pathogenesis of moyamoya disease (MMD) is unclear. Inflammation and immune imbalance have been identified as potential factors contributing to the occurrence and...
BACKGROUND
The pathogenesis of moyamoya disease (MMD) is unclear. Inflammation and immune imbalance have been identified as potential factors contributing to the occurrence and progression of MMD. However, the specific proteins and metabolites responsible for triggering this process are yet to be established. The purpose of this study is to identify differentially expressed proteins and metabolites in patients with MMD and perform Kyoto Encyclopedia of Genes and Genomes pathway integration analysis to pinpoint crucial proteins and metabolites involved in the disease.
METHODS
We performed untargeted metabolomic and data-independent acquisition proteomic analyses on the serum samples of individuals with MMD and healthy controls (HC).
RESULTS
In patients with MMD versus HC, 24 proteins and 60 metabolites, including 21 anionic metabolites and 39 cationic metabolites, which were significantly different, were identified. In patients with MMD, several proteins involved in inflammation and immune metabolism, such as tubulin beta-6 and complement C4, were found to have significantly altered levels. Similarly, many metabolites involved in inflammation and immune metabolisms, such as dimethyl 4-hydroxyisophthalate, beta-nicotinamide mononucleotide, 2-(3-(4-pyridyl)-1H-1,2,4-triazol-5-yl)pyridine, and PC (17:1/18:2), were significantly altered. Intriguingly, these proteins and metabolites are involved in the progression of atherosclerosis through immune and inflammatory pathways, although some have never been reported in MMD. Moreover, integrated proteomics and metabolomics studies were conducted to determine shared pathways involving cholesterol metabolism, vitamin digestion, fat digestion, and absorption pathways of proteins and metabolites, which warrant further investigation.
CONCLUSIONS
Significant increases in pro-inflammatory and immunosuppressive abilities have been observed in patients with MMD, accompanied by significant reductions in anti-inflammatory and immune regulation. Various metabolites and proteins implicated in these processes have been identified for the first time. These findings hold immense significance for comprehending the pathogenesis of MMD and for the development of future drug therapies.
Topics: Humans; Moyamoya Disease; Proteomics; Metabolomics; Inflammation
PubMed: 37962021
DOI: 10.1002/brb3.3328 -
Transactions of the Royal Society of... Sep 2023Snakebite envenoming is an important public health issue in many tropical and subtropical countries, where the burden of morbidity and mortality falls particularly on... (Review)
Review
Snakebite envenoming is an important public health issue in many tropical and subtropical countries, where the burden of morbidity and mortality falls particularly on impoverished rural communities. Children are an especially vulnerable group. This scoping review provides an overview of the extent, type and content of peer-reviewed evidence regarding factors associated with mortality in snakebite-envenomed children. A comprehensive literature search of MEDLINE and the Global Index Medicus yielded 623 articles, of which 15 met the criteria for inclusion; 67% of studies were conducted in India, with the remaining studies taking place in Papua New Guinea, Morocco and The Gambia. There was a notable scarcity of eligible studies from sub-Saharan Africa and Latin America despite the high burden of envenoming in these regions. The risk factors for mortality that were identified by the greatest number of studies were younger patient age (n=4), delay in administration of antivenom (n=4) and acute kidney injury (n=3). Identification of poor prognostic factors can assist clinicians in making timely referrals to centres with paediatric critical care capability. Future research must address the lack of studies from key geographical regions so that evidence-based improvements to the care of this vulnerable group can be implemented.
Topics: Humans; Snake Bites; Antivenins; Africa South of the Sahara; Public Health; Gambia
PubMed: 37264929
DOI: 10.1093/trstmh/trad031 -
Toxins Oct 2023Amidst the global healthcare landscape, the menace of snakebite envenoming (SBE) has persisted, silently afflicting millions and annually claiming tens of thousands of...
Amidst the global healthcare landscape, the menace of snakebite envenoming (SBE) has persisted, silently afflicting millions and annually claiming tens of thousands of lives [...].
Topics: Humans; Snake Bites; Delivery of Health Care; Pentaerythritol Tetranitrate; Antivenins
PubMed: 37999489
DOI: 10.3390/toxins15110626 -
Frontiers in Immunology 2023Effective respiratory syncytial virus (RSV) vaccines have been developed and licensed for elderly adults and pregnant women but not yet for infants and young children....
Effective respiratory syncytial virus (RSV) vaccines have been developed and licensed for elderly adults and pregnant women but not yet for infants and young children. The RSV immune state of the young child, i.e., previously RSV infected or not, is important to the conduct and interpretation of epidemiology studies and vaccine clinical trials. To address the need for sensitive assays to detect immunologic evidence of past infection, we developed, characterized, and evaluated 7 assays including 4 IgG antibody enzyme immunoassays (EIAs), two neutralizing antibody assays, and an IFN-γ EliSpot (EliSpot) assay. The four IgG EIAs used a subgroup A plus subgroup B RSV-infected Hep-2 cell lysate antigen (Lysate), an expressed RSV F protein antigen (F), an expressed subgroup A G protein antigen (Ga), or an expressed subgroup B G protein (Gb) antigen. The two neutralizing antibody assays used either a subgroup A or a subgroup B RSV strain. The EliSpot assay used a sucrose cushion purified combination of subgroup A and subgroup B infected cell lysate. All seven assays had acceptable repeatability, signal against control antigen, lower limit of detection, and, for the antibody assays, effect of red cell lysis, lipemia and anticoagulation of sample on results. In 44 sera collected from children >6 months after an RSV positive illness, the lysate, F, Ga and Gb IgG EIAs, and the subgroup A and B neutralizing antibody assays, and the EliSpot assays were positive in 100%, 100%, 86%, 95%, 43%, and 57%, respectively. The Lysate and F EIAs were most sensitive for detecting RSV antibody in young children with a documented RSV infection. Unexpectedly, the EliSpot assay was positive in 9/15 (60%) of PBMC specimens from infants not exposed to an RSV season, possibly from maternal microchimerism. The Lysate and F EIAs provide good options to reliably detect RSV antibodies in young children for epidemiologic studies and vaccine trials.
Topics: Adult; Infant; Child; Humans; Female; Pregnancy; Child, Preschool; Aged; Respiratory Syncytial Virus Infections; Leukocytes, Mononuclear; Antibodies, Neutralizing; Antibodies, Viral; Respiratory Syncytial Virus Vaccines; Antigens, Viral; Immunoglobulin G; GTP-Binding Proteins
PubMed: 38283339
DOI: 10.3389/fimmu.2023.1332772 -
Frontiers in Immunology 2023Unlike glycosylation of proteins expressed in mammalian systems, bacterial glycosylation is often neglected in the development of recombinant vaccines.
INTRODUCTION
Unlike glycosylation of proteins expressed in mammalian systems, bacterial glycosylation is often neglected in the development of recombinant vaccines.
METHODS
Here, we compared the effects of glycosylation of YghJ, an protein important for mucus attachment of bacteria causing in urinary tract infections (UTIs). A novel method based on statistical evaluation of phage display for the identification and comparison of epitopes and mimotopes of anti-YghJ antibodies in the sera was used. This is the first time that the effect of glycosylation of a recombinant bacterial antigen has been studied at the peptide epitope level.
RESULTS
The study identifies differences in the immune response for (non)-glycosylated antigens in rabbits and pigs and compares them to a large group of patients with UTI, which have been diagnosed as positive for various bacterial pathogens. We identified glycosylation-specific peptide epitopes, a large immunological similarity between different UTI pathogens, and a broad peptide epitope pattern in patients and animals, which could result in a variable response in patients upon vaccination.
DISCUSSION
This epitope analysis indicates that the vaccination of rabbits and pigs raises antibodies that translate well into the human immune system. This study underlines the importance of glycosylation in bacterial vaccines and provides detailed immune diagnostic methods to understand individual immune responses to vaccines.
Topics: Humans; Rabbits; Swine; Animals; Epitopes; Antigens, Bacterial; Glycosylation; Escherichia coli; Urinary Tract Infections; Peptides; Mammals; Escherichia coli Proteins; Metalloproteases
PubMed: 37954588
DOI: 10.3389/fimmu.2023.1258136