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Vaccines Jun 2024Currently, allergen-specific immunotherapy (AIT) for ragweed allergy is still based on natural allergen extracts. This study aimed to analyse the ability of four...
Currently, allergen-specific immunotherapy (AIT) for ragweed allergy is still based on natural allergen extracts. This study aimed to analyse the ability of four commercially available AIT vaccines (CLUSTOID, TYRO-SIT, POLLINEX Quattro Plus and Diater Depot) regarding their ability to induce IgG antibodies against ragweed pollen allergens in rabbits. Accordingly, the IgG reactivity of AIT-induced rabbit sera was tested for ten different ragweed pollen allergens (Amb a 1, 3, 4, 5, 6, 8, 9, 10, 11 and 12) by an ELISA. Furthermore, the ability of rabbit AIT-specific sera to block allergic patients' IgE binding to relevant ragweed allergens (Amb a 1, 4, 6, 8 and 11) and to inhibit allergen-induced basophil activation was evaluated by an IgE inhibition ELISA and a mediator release assay. Only two AIT vaccines (Diater Depot > CLUSTOID) induced relevant IgG antibody levels to the major ragweed allergen Amb a 1. The IgG responses induced by the AIT vaccines against the other ragweed allergens were low and highly heterogeneous. Interestingly, the kinetics of IgG responses were different among the AIT vaccines and even within one AIT vaccine (Diater Depot) for Amb a 1 (long-lasting) versus Amb a 8 and Amb a 11 (short-lived). This could be due to variations in allergen contents, the immunogenicity of the allergens, and different immunization protocols. The IgE inhibition experiments showed that rabbit AIT-specific sera containing high allergen-specific IgG levels were able to inhibit patients' IgE binding and prevent the mediator release with Diater Depot. The high levels of allergen-specific IgG levels were associated with their ability to prevent the recognition of allergens by patients' IgE and allergen-induced basophil activation, indicating that the measurement of allergen-induced IgG could be a useful surrogate marker for the immunological efficacy of vaccines. Accordingly, the results of our study may be helpful for the selection of personalized AIT vaccination strategies for ragweed-allergic patients.
PubMed: 38932364
DOI: 10.3390/vaccines12060635 -
Viruses Jun 2024Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host... (Review)
Review
Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host cell proteases by human viruses, focusing on those with primarily respiratory tropism, particularly SARS-CoV-2. We first describe the various classes of proteases present in the respiratory tract, as well as elsewhere in the body, and incorporate the targeting of these proteases as therapeutic drugs for use in humans. Host cell proteases are also linked to the systemic spread of viruses and play important roles outside of the respiratory tract; therefore, we address how proteases affect viruses across the spectrum of infections that can occur in humans, intending to understand the extrapulmonary spread of SARS-CoV-2.
Topics: Humans; Respiratory Tract Infections; SARS-CoV-2; Peptide Hydrolases; Viral Tropism; COVID-19; Virus Diseases; Antiviral Agents; Host-Pathogen Interactions; Protease Inhibitors
PubMed: 38932275
DOI: 10.3390/v16060984 -
Viruses Jun 2024Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various...
BACKGROUND
Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases' pathogenesis. Nevertheless, our understanding of respiratory microbiota is limited by technical constraints, predominantly focusing on bacteria and neglecting crucial populations like viruses. Despite recent efforts to improve our understanding of viral diversity in the human body, our knowledge of viral diversity associated with the human respiratory tract remains limited.
METHODS
Following a comprehensive search in bibliographic and sequencing data repositories using keyword terms, we retrieved shotgun metagenomic data from public repositories (n = 85). After manual curation, sequencing data files from 43 studies were analyzed using EVEREST (pipEline for Viral assEmbly and chaRactEriSaTion). Complete and high-quality contigs were further assessed for genomic and taxonomic characterization.
RESULTS
Viral contigs were obtained from 194 out of the 868 FASTQ files processed through EVEREST. Of the 1842 contigs that were quality assessed, 8% (n = 146) were classified as complete/high-quality genomes. Most of the identified viral contigs were taxonomically classified as bacteriophages, with taxonomic resolution ranging from the superkingdom level down to the species level. Captured contigs were spread across 25 putative families and varied between RNA and DNA viruses, including previously uncharacterized viral genomes. Of note, airway samples also contained virus(es) characteristic of the human gastrointestinal tract, which have not been previously described as part of the lung virome. Additionally, by performing a meta-analysis of the integrated datasets, ecological trends within viral populations linked to human disease states and their biogeographical distribution along the respiratory tract were observed.
CONCLUSION
By leveraging publicly available repositories of shotgun metagenomic data, the present study provides new insights into viral genomes associated with specimens from the human respiratory tract across different disease spectra. Further studies are required to validate our findings and evaluate the potential impact of these viral communities on respiratory tract physiology.
Topics: Humans; Metagenomics; Virome; Genome, Viral; Respiratory System; Viruses; Metagenome; Computer Simulation; Phylogeny; Computational Biology; Microbiota; Bacteriophages
PubMed: 38932245
DOI: 10.3390/v16060953 -
Viruses May 2024The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide....
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential of cannabis compounds as therapeutic agents against SARS-CoV-2 through their interaction with the virus's papain-like protease (PLpro) protein, a crucial element in viral replication and immune evasion. Computational methods, including molecular docking and molecular dynamics (MD) simulations, were employed to screen cannabis compounds against PLpro and analyze their binding mechanisms and interaction patterns. The results showed cannabinoids with binding affinities ranging from -6.1 kcal/mol to -4.6 kcal/mol, forming interactions with PLpro. Notably, Cannabigerolic and Cannabidiolic acids exhibited strong binding contacts with critical residues in PLpro's active region, indicating their potential as viral replication inhibitors. MD simulations revealed the dynamic behavior of cannabinoid-PLpro complexes, highlighting stable binding conformations and conformational changes over time. These findings shed light on the mechanisms underlying cannabis interaction with SARS-CoV-2 PLpro, aiding in the rational design of antiviral therapies. Future research will focus on experimental validation, optimizing binding affinity and selectivity, and preclinical assessments to develop effective treatments against COVID-19.
Topics: Molecular Dynamics Simulation; SARS-CoV-2; Cannabinoids; Molecular Docking Simulation; Humans; Antiviral Agents; Coronavirus Papain-Like Proteases; Protein Binding; COVID-19 Drug Treatment; Virus Replication; Protease Inhibitors
PubMed: 38932170
DOI: 10.3390/v16060878 -
Viruses May 2024The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon...
The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon gene (STING) is an essential component of the host defense mechanisms against respiratory viral infections. Although the role of the cGAS/STING signaling axis in the innate immune response to DNA viruses has been thoroughly characterized, mounting evidence shows that it also plays a key role in the prevention of RNA virus infections. In this study, we investigated the role of STING activation during Influenza virus (IFV) infection. In both mouse bone marrow-derived macrophages and monocytic cell line THP-1 differentiated with PMA, we found that dimeric amidobenzimidazole (diABZI), a STING agonist, had substantial anti-IFV activity against multiple strains of IFV, including A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. On the other hand, a pharmacological antagonist of STING (H-151) or the loss of STING in human macrophages leads to enhanced viral replication but suppressed IFN expression. Furthermore, diABZI was antiviral against IFV in primary air-liquid interface cultures of nasal epithelial cells. Our data suggest that STING agonists may serve as promising therapeutic antiviral agents to combat IFV.
Topics: Animals; Humans; Immunity, Innate; Mice; Antiviral Agents; Macrophages; Membrane Proteins; THP-1 Cells; Virus Replication; Influenza, Human; Dogs; Mice, Inbred C57BL; Orthomyxoviridae Infections; Orthomyxoviridae; Benzimidazoles; Signal Transduction
PubMed: 38932148
DOI: 10.3390/v16060855 -
Viruses May 2024The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple... (Review)
Review
The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.
Topics: SARS-CoV-2; Humans; COVID-19; Animals; Spike Glycoprotein, Coronavirus; Mice; Post-Acute COVID-19 Syndrome; Angiotensin-Converting Enzyme 2; Peptides; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 38932130
DOI: 10.3390/v16060838 -
Pharmaceutics Jun 2024Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with... (Review)
Review
Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alternatives that are better tolerated but equally or more effective. Therefore, this review aims to identify and explore the novel alternative oxazolidinones to potentially replace linezolid in the management of TB. The keywords tuberculosis and oxazolidinones were searched in PubMed to identify eligible compounds. The individual drug compounds were then searched with the term tuberculosis to identify the relevant in vitro, in vivo and clinical studies. The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. An additional search resulted in 32 preclinical and 21 clinical studies. All novel oxazolidinones except posizolid and eperezolid resulted in positive preclinical outcomes. Sutezolid and delpazolid completed early phase 2 clinical studies with better safety and equal or superior efficacy. Linezolid is expected to continue as the mainstay therapy, with renewed interest in drug monitoring. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens.
PubMed: 38931939
DOI: 10.3390/pharmaceutics16060818 -
Sensors (Basel, Switzerland) Jun 2024The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will...
The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will be reached by 2050. This paper presents an innovative AIoT-enabled data fusion system implemented at the CMUH Respiratory Intensive Care Unit (RICU) to address the high incidence of medical errors in ICUs, which are among the top three causes of mortality in healthcare facilities. ICU patients are particularly vulnerable to medical errors due to the complexity of their conditions and the critical nature of their care. We introduce a four-layer AIoT architecture designed to manage and deliver both real-time and non-real-time medical data within the CMUH-RICU. Our system demonstrates the capability to handle 22 TB of medical data annually with an average delay of 1.72 ms and a bandwidth of 65.66 Mbps. Additionally, we ensure the uninterrupted operation of the CMUH-RICU with a three-node streaming cluster (called Kafka), provided a failed node is repaired within 9 h, assuming a one-year node lifespan. A case study is presented where the AI application of acute respiratory distress syndrome (ARDS), leveraging our AIoT data fusion approach, significantly improved the medical diagnosis rate from 52.2% to 93.3% and reduced mortality from 56.5% to 39.5%. The results underscore the potential of AIoT in enhancing patient outcomes and operational efficiency in the ICU setting.
Topics: Intensive Care Units; Humans; Artificial Intelligence; Respiratory Distress Syndrome
PubMed: 38931713
DOI: 10.3390/s24123929 -
Sensors (Basel, Switzerland) Jun 2024Due to limitations in current motion tracking technologies and increasing interest in alternative sensors for motion tracking both inside and outside the MRI system, in...
Due to limitations in current motion tracking technologies and increasing interest in alternative sensors for motion tracking both inside and outside the MRI system, in this study we share our preliminary experience with three alternative sensors utilizing diverse technologies and interactions with tissue to monitor motion of the body surface, respiratory-related motion of major organs, and non-respiratory motion of deep-seated organs. These consist of (1) a Pilot-Tone RF transmitter combined with deep learning algorithms for tracking liver motion, (2) a single-channel ultrasound transducer with deep learning for monitoring bladder motion, and (3) a 3D Time-of-Flight camera for observing the motion of the anterior torso surface. Additionally, we demonstrate the capability of these sensors to simultaneously capture motion data outside the MRI environment, which is particularly relevant for procedures like radiation therapy, where motion status could be related to previously characterized cyclical anatomical data. Our findings indicate that the ultrasound sensor can track motion in deep-seated organs (bladder) as well as respiratory-related motion. The Time-of-Flight camera offers ease of interpretation and performs well in detecting surface motion (respiration). The Pilot-Tone demonstrates efficacy in tracking bulk respiratory motion and motion of major organs (liver). Simultaneous use of all three sensors could provide complementary motion information outside the MRI bore, providing potential value for motion tracking during position-sensitive treatments such as radiation therapy.
Topics: Humans; Magnetic Resonance Imaging; Respiration; Liver; Movement; Urinary Bladder; Algorithms; Deep Learning; Motion; Ultrasonography
PubMed: 38931494
DOI: 10.3390/s24123710 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Physicians are currently finding products for pediatric respiratory diseases of viral etiology to reduce the inappropriate use of antibiotic therapy. This study...
The Effectiveness of a Dietary Supplement with Honey, Propolis, Extract, and Zinc in Children Affected by Acute Tonsillopharyngitis: An Open, Randomized, and Controlled Trial.
Physicians are currently finding products for pediatric respiratory diseases of viral etiology to reduce the inappropriate use of antibiotic therapy. This study evaluated PediaFlù (Pediatrica S.r.l.), a dietary supplement already on the market composed of honey, propolis, extract, and zinc (DSHPP), in children affected by acute tonsillopharyngitis (ATR). The open-label, randomized, and controlled study compared DSHPP + standard of care (SoC) versus SoC alone for six days. Children between 3 and 10 years with an ATR ≤ 48 h, a negative rapid test for beta-hemolytic , or a culture identification of nasal and/or pharyngeal exudates were included. A tonsillitis severity score (TSS) and the number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) were the primary endpoints. DSHPP+ SoC showed better performance than SoC alone for TSS sub-scores: throat pain and erythema on day 6 ( < 0.001 and < 0.05), swallowing ( < 0.01 on day 4), and TSS total score on days 4 and 6 ( < 0.05 and < 0.001). Only one patient (SoC group) had treatment failure for ibuprofen administration. No adverse events were reported. DSHPP is an optimal adjuvant in the treatment of URTI and could potentially be useful in the daily clinical practice of paediatricians evaluating the correct antibiotic prescription.
PubMed: 38931472
DOI: 10.3390/ph17060804