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Frontiers in Bioscience (Landmark... May 2024To investigate the immune responses and protection ability of ultraviolet light (UV)-inactivated recombinant vesicular stomatitis (rVSV)-based vectors that expressed a...
BACKGROUND
To investigate the immune responses and protection ability of ultraviolet light (UV)-inactivated recombinant vesicular stomatitis (rVSV)-based vectors that expressed a fusion protein consisting of four copies of the influenza matrix 2 protein ectodomain (tM2e) and the Dendritic Cell (DC)-targeting domain of the Ebola Glycoprotein (EΔM), (rVSV-EΔM-tM2e).
METHOD
In our previous study, we demonstrated the effectiveness of rVSV-EΔM-tM2e to induce robust immune responses against influenza M2e and protect against lethal challenges from H1N1 and H3N2 strains. Here, we used UV to inactivate rVSV-EΔM-tM2e and tested its immunogenicity and protection in BALB/c mice from a mouse-adapted H1N1 influenza challenge. Using Enzyme-Linked Immunosorbent Assay (ELISA) and Antibody-Dependent Cellular Cytotoxicity (ADCC), the influenza anti-M2e immune responses specific to human, avian and swine influenza strains induced were characterized. Likewise, the specificity of the anti-M2e immune responses induced in recognizing M2e antigen on the surface of the cell was investigated using Fluorescence-Activated Cell Sorting (FACS) analysis.
RESULTS
Like the live attenuated rVSV-EΔM-tM2e, the UV-inactivated rVSV-EΔM-tM2e was highly immunogenic against different influenza M2e from strains of different hosts, including human, swine, and avian, and protected against influenza H1N1 challenge in mice. The FACS analysis demonstrated that the induced immune responses can recognize influenza M2 antigens from human, swine and avian influenza strains. Moreover, the rVSV-EΔM-tM2e also induced ADCC activity against influenza M2e from different host strains.
CONCLUSIONS
These findings suggest that UV-inactivated rVSV-EΔM-tM2e could be used as an inactivated vaccine against influenza viruses.
Topics: Animals; Influenza Vaccines; Influenza A Virus, H1N1 Subtype; Ultraviolet Rays; Mice, Inbred BALB C; Orthomyxoviridae Infections; Female; Mice; Humans; Viral Matrix Proteins; Vesiculovirus; Vaccines, Inactivated
PubMed: 38812326
DOI: 10.31083/j.fbl2905195 -
BMC Oral Health May 2024This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and...
INTRODUCTION
This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT).
METHODS
Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified.
RESULTS
95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT.
CONCLUSION
This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results.
CLINICAL SIGNIFICANCE
The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL).
RESEARCH QUESTION
What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients?
AIM
To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy.
NULL HYPOTHESIS
There is no association between salivary proteins and onset/severity of OM in HNC patients.
Topics: Humans; Longitudinal Studies; Head and Neck Neoplasms; Stomatitis; Male; Salivary Proteins and Peptides; Female; Middle Aged; Radiotherapy, Intensity-Modulated; Aged; Saliva; Adult; alpha-Amylases
PubMed: 38811865
DOI: 10.1186/s12903-024-04400-9 -
BioRxiv : the Preprint Server For... May 2024The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic...
The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-β expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in murine and human cells, providing a cGAS stimulus. N-acetylcysteine decreased IFN-β induction by TPG, implicating reactive oxygen species (ROS). However, mitoTEMPO, a mitochondrial oxidative stress inhibitor did not impact TPG-induced IFN. On the other hand, inhibiting the inositol requiring enzyme 1 (IRE1) ER stress sensor and its target transcription factor XBP1 decreased the generation of cytosolic dsDNA. iNOS upregulation was XBP1-dependent, and an iNOS inhibitor decreased cytosolic dsDNA and IFN-β, implicating ROS downstream of the IRE1-XBP1 pathway. Inhibition of the PKR-like ER kinase (PERK) pathway also attenuated cytoplasmic dsDNA release. The PERK-regulated apoptotic factor Bim was required for both dsDNA release and IFN-β mRNA induction. Finally, XBP1 and PERK pathways contributed to cytosolic dsDNA release and IFN-induction by the RNA virus, Vesicular Stomatitis Virus (VSV). Together, our findings suggest that ER stressors, including viral pathogens without nominal STING or cGAS ligands such as RNA viruses, trigger multiple canonical UPR pathways that cooperate to activate STING and downstream IFN-β via mitochondrial dsDNA release.
PubMed: 38798499
DOI: 10.1101/2024.05.10.593557 -
British Dental Journal May 2024Peri-implant diseases are frequent complications that occur around osseointegrated endosseous implants and are the result of an imbalance between the bacterial challenge... (Review)
Review
Peri-implant diseases are frequent complications that occur around osseointegrated endosseous implants and are the result of an imbalance between the bacterial challenge and host response. Peri-implant diseases may affect the peri-implant mucosa only (peri-implant mucositis) or also involve the supporting bone (peri-implantitis). Early detection of peri-implant diseases and timely treatment is important for the success of dental implant treatment. Peri-implant probing is essential to assess the peri-implant health status and should be done at each recall visit. Dental practitioners should be familiar with the clinical and radiological features of both conditions in order to make an accurate diagnosis and determine the appropriate treatment required. This article aims to provide clinicians with an understanding of the key differences between peri-implant health, peri-implant mucositis and peri-implantitis.
Topics: Humans; Peri-Implantitis; Dental Implants; Stomatitis; Mucositis
PubMed: 38789756
DOI: 10.1038/s41415-024-7402-z -
Journal of Fungi (Basel, Switzerland) Apr 2024Denture stomatitis (DS) is a very common disease in wearers of removable complete and partial dentures with a worldwide prevalence in the range of 20-67%. Both... (Review)
Review
Denture stomatitis (DS) is a very common disease in wearers of removable complete and partial dentures with a worldwide prevalence in the range of 20-67%. Both industrially developed and impoverished nations are affected by the illness. DS is often associated with ill-fitting dentures or a fungal infection with spp. is normally found in the oral cavity microbiota, but it can be harmful to the health of elderly people with underlying diseases. Therefore, the purpose of the present study is to offer the most recent information about the epidemiology, etiology, and global distribution of species associated with DS through a systematic review. Several databases, including Medline, Web of Science, and Scopus, were used to conduct an extensive search of the literature published in the previous 20 years. The selection of studies was performed by two authors. The extracted data were as follows: author, year of publication, country, sample, frequency of DS, method of diagnosing stomatitis, species of , risk factors, and etiology of the disease. The JBI Critical appraisal tools were used to assess the quality of the studies. Eventually, twenty-eight studies were included in the systematic review. Twenty-one studies investigated DS, while seven studies examined colonization in patients using removable dentures. The results show that the main causes of DS include the type of dentures, continuous wearing of dentures, and the formation of a biofilm, which is facilitated by poor dental hygiene. Additionally, previous studies have pinpointed the significance of the salivary flow, saliva composition, and salivary pH. The findings of the current review indicate that it is crucial to monitor denture wearers for the appearance of DS, especially the patients whose immunity has been impaired due to a systemic condition. Finally, frequent follow-ups should include a clinical examination and microbial swabs of the palatal mucosa and the mucosal surface of the denture.
PubMed: 38786683
DOI: 10.3390/jof10050328 -
Biomolecules May 2024Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral... (Review)
Review
Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.
Topics: Humans; Randomized Controlled Trials as Topic; Anti-Inflammatory Agents; Chemoradiotherapy; Mucositis; Neoplasms; Stomatitis
PubMed: 38785967
DOI: 10.3390/biom14050560 -
Virus Research May 2024Parapoxviruses (PPV) of animals are spread worldwide. While the Orf virus (ORFV) species is a molecularly well-characterized prototype pathogen of small ruminants, the...
Parapoxviruses (PPV) of animals are spread worldwide. While the Orf virus (ORFV) species is a molecularly well-characterized prototype pathogen of small ruminants, the genomes of virus species affecting large ruminants, namely Bovine papular stomatitis virus (BPSV) and Pseudocowpox virus (PCPV), are less well known. Using Nanopore sequencing we retrospectively show the whole genome sequences (WGS) of six BPSV, three PCPV isolates and an attenuated ORFV strain, originating from different geographic locations. A phylogenetic tree shows that the de novo assembled genomes belong to PPV species including WGS of reference PPV. Remarkably, Nanopore sequencing allowed the molecular resolution of inverted terminal repeats (ITR) and the hairpin loop within the de novo assembled WGS. Additionally, peculiarities regarding map location of two genes and the heterogeneity of a genomic region were noted. Details for the molecular variability of an interferon response modulatory gene (ORF116) and the PCPV specificity of gene 073.5 are reported. In summary, WGS gained by Nanopore sequencing allowed analysis of complete PPV genomes and confident virus species attribution within a phylogenetic tree avoiding uncertainty of limited gene-based diagnostics. Nanopore-based WGS provides robust comparison of PPV genomes and reliable identity determination of new Poxviruses.
PubMed: 38782262
DOI: 10.1016/j.virusres.2024.199404 -
PloS One 2024The aim of this systematic review was to describe the efficacy and acceptability of natural products in the management of oral mucositis caused by radiation. From the...
The aim of this systematic review was to describe the efficacy and acceptability of natural products in the management of oral mucositis caused by radiation. From the day it started to August 7, 2023, a thorough search for randomized controlled trials (RCTs) was carried out among seven databases: the Web of Science, PubMed, Embase, OVID, Scopus, the Cochrane Library and the CINAHL database. Only English-language articles were identified during the search. Using the revised Cochrane risk-of-bias tool, version 2, two researchers screened the articles, collected information on study characteristics, and appraised risks of bias. The data were analyzed and descriptively presented with a narrative synthesis methodology involving the Synthesis Without Meta-Analysis (SWiM) reporting element applied in detail. The PROSPERO registration number of this study is CRD42023476932. Thirty-six clinical trials were included in the study; the included studies included a variety of 20 types of natural products. Honey and Curcuma longa were the most commonly assessed natural products. A total of 2,400 participants reported taking part in therapy with natural products for oral mucositis. Natural products demonstrated substantial efficacy in terms of influencing intensity, incidence, pain score, quality of life, and symptoms such as xerostomia and dysphagia. Except for manuka honey, most natural products were well accepted. Regarding the clinical trials' risk of bias, 2 clinical trials (5.56%) had a high risk of bias, 17 studies (47.2%) had a low risk of bias, and 17 studies (47.2%) were rated with "some concern." Natural remedies work well as alternate treatments for managing oral mucositis caused by radiation therapy. However, additional clinical trials are still needed. The safety of these conventional medications as well as their effectiveness and safety when used in combination with other conventional or naturopathic therapies should be fully examined.
Topics: Humans; Stomatitis; Biological Products; Radiotherapy; Radiation Injuries; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38781255
DOI: 10.1371/journal.pone.0303988 -
Virus Evolution 2024Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can infect various human tissues and cell types, principally via interaction with its cognate receptor...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can infect various human tissues and cell types, principally via interaction with its cognate receptor angiotensin-converting enzyme-2 (ACE2). However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study the adaptation of the SARS-CoV-2 spike to four human cell lines expressing different levels of key entry factors. After twenty passages of a spike-expressing recombinant vesicular stomatitis virus (VSV), cell-type-specific phenotypic changes were observed and sequencing allowed the identification of sixteen adaptive spike mutations. We used VSV pseudotyping to measure the entry efficiency, ACE2 affinity, spike processing, TMPRSS2 usage, and entry pathway usage of all the mutants, alone or in combination. The fusogenicity of the mutant spikes was assessed with a cell-cell fusion assay. Finally, mutant recombinant VSVs were used to measure the fitness advantage associated with selected mutations. We found that the effects of these mutations varied across cell types, both in terms of viral entry and replicative fitness. Interestingly, two spike mutations (L48S and A372T) that emerged in cells expressing low ACE2 levels increased receptor affinity, syncytia induction, and entry efficiency under low-ACE2 conditions. Our results demonstrate specific adaptation of the SARS-CoV-2 spike to different cell types and have implications for understanding SARS-CoV-2 tissue tropism and evolution.
PubMed: 38779130
DOI: 10.1093/ve/veae032 -
Archives of Rheumatology Mar 2024This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis,...
OBJECTIVES
This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients.
PATIENTS AND METHODS
This study retrospectively analyzed the antibody test results of 20 pediatric patients (10 males, 10 females; mean age: 2.5±1.5 years; range, 0.5 to 5.4 years) with and without flare who were initially evaluated for a number of underlying diseases due to periodic fever/infectious symptoms but then diagnosed with PFAPA between January 2015 and December 2020. Antibody levels were determined by chemiluminescence microparticle immunoassay. The results were retrospectively compared with a group of healthy children after the PFAPA diagnosis was confirmed.
RESULTS
The chemiluminescence microparticle immunoassay revealed 35%, 65%, 20%, 86.6%, and 55% of PFAPA cases with low serum levels of IgA, IgG, IgG2, IgG3, and IgM respectively, while 56.2% had high IgE levels. Moreover, low serum levels of at least two antibody classes or subclasses were reported in 80% of the PFAPA children. While cases with low IgG serum levels were with the highest incidence rates among the low IgG3 PFAPA patient population, both high IgE and low IgM cases were common in the rest of the patients.
CONCLUSION
Our results suggest an association between PFAPA and low serum antibody levels, particularly of IgG3. Future studies are needed to confirm our conclusion.
PubMed: 38774691
DOI: 10.46497/ArchRheumatol.2023.9988