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Frontiers in Genetics 2024Epicardial cells regulate heart growth by secreting numerous growth factors and undergoing lineage specification into other cardiac lineages. However, the lack of...
Epicardial cells regulate heart growth by secreting numerous growth factors and undergoing lineage specification into other cardiac lineages. However, the lack of specific marker genes for epicardial cells has hindered the understanding of this cell type in heart development. Through the analysis of a cardiac single cell mRNA sequencing dataset, we identified a novel epicardial gene named (). Further analysis of the expression patterns of and , a well-known epicardial gene, revealed their preferences in major cardiac cell types. Using lineage-tracing analysis, we analyzed labeled cells at multiple time windows and found that it labels epicardial cells at both embryonic and neonatal stages. Furthermore, we studied the function of epicardial cells using a diphtheria toxin A chain (DTA)-based cell ablation system. We discovered that labeled cells are essential for fetal heart development. Finally, we investigated the function of and labeled cells in neonatal mouse development. We observed that the ; mice displayed a smaller size after tamoxifen treatment, suggesting the potential importance of labeled cells in neonatal mouse development. Additionally, we found that ; mice died at early stages, likely due to defects in the kidney and spleen. In summary, we have identified as a new epicardial cell marker gene and further explored the function of epicardial cells using the and -mediated DTA ablation system.
PubMed: 38831775
DOI: 10.3389/fgene.2024.1385867 -
Reproductive Toxicology (Elmsford, N.Y.) May 2024In the recent paper by Lee et al. reporting reproductive toxicity testing of BVN008, a newly developed tetanus, diphtheria, and acellular pertussis vaccine, the...
In the recent paper by Lee et al. reporting reproductive toxicity testing of BVN008, a newly developed tetanus, diphtheria, and acellular pertussis vaccine, the statement is made "BVN008 is a booster vaccine identical to the current Tdap vaccines, Boostrix (GSK) and Adacel (Sanofi)." However, as the authors report, the acellular pertussis portion of BVN008 was provided by BIKEN (Japan). The composition of the BIKEN acellular pertussis product differs in important ways from the compositions of the acellular pertussis components of Boostrix and Adacel. Accordingly, the statement cited above is incorrect. A more appropriate statement might have been, "BVN008 is a booster vaccine similar in concept to the current Tdap vaccines, Boostrix (GSK) and Adacel (Sanofi)."
PubMed: 38823463
DOI: 10.1016/j.reprotox.2024.108627 -
Otolaryngology--head and Neck Surgery :... Jun 2024Since the introduction of vaccines for severe acute respiratory syndrome coronavirus 2 in the United States, there has been significant vaccine hesitancy, in part due...
Since the introduction of vaccines for severe acute respiratory syndrome coronavirus 2 in the United States, there has been significant vaccine hesitancy, in part due to fear of adverse effects. We sought to investigate the rates of smell and taste changes after COVID-19 vaccination compared to other common vaccines. Our study cohort included individuals identified by Current Procedural Terminology code in the TriNetX database receiving the COVID-19 first series, COVID-19 booster, influenza, tetanus, diphtheria, pertussis (TDAP), or pneumococcal vaccines between December 15, 2020, and August 15, 2023. After 1:1 propensity score matching, postvaccination incidence of disturbance of smell and taste was significantly less likely after COVID-19 first series vaccine compared to influenza (odds ratios, OR: 0.27 [95% confidence interval, CI: 0.20-0.36]), TDAP (OR: 0.35 [95% CI: 0.26-0.47]), and pneumococcal vaccines (OR: 0.17 [95% CI: 0.09-0.32]). Similarly, incidence of disturbance of smell and taste was significantly less likely after COVID-19 booster vaccine compared to the influenza (OR: 0.60 [95% CI: 0.48-0.76]), TDAP (OR: 0.63 [95% CI: 0.47-0.85]), and pneumococcal vaccines (OR: 0.44 [95% CI: 0.28-0.68]). This study builds upon the literature demonstrating the safety of COVID-19 vaccination.
PubMed: 38822762
DOI: 10.1002/ohn.833 -
Iranian Journal of Allergy, Asthma, and... Apr 2024During epithelial to mesenchymal transition, the ability of cancer cells to transform and metastasize is primarily determined by N-cadherin-mediated migration and...
During epithelial to mesenchymal transition, the ability of cancer cells to transform and metastasize is primarily determined by N-cadherin-mediated migration and invasion. This study aimed to evaluate whether the N-cadherin promoter can induce diphtheria toxin expression as a suicide gene in epithelial to mesenchymal transition (EMT)-induced cancer cells and whether this can be used as potential gene therapy. To investigate the expression of diphtheria toxin under the N-cadherin promoter, the promoter was synthesized, and was cloned upstream of diphtheria toxin in a pGL3-Basic vector. The A-549 cells was transfected by electroporation. After induction of EMT by TGF-β and hypoxia treatment, the relative expression of diphtheria toxin, mesenchymal genes such as N-cadherin and Vimentin, and epithelial genes such as E-cadherin and β-catenin were measured by real-time PCR. MTT assay was also performed to measure cytotoxicity. Finally, cell motility was assessed by the Scratch test. After induction of EMT in transfected cells, the expression of mesenchymal markers such as Vimentin and N-cadherin significantly decreased, and the expression of β-catenin increased. In addition, the MTT assay showed promising toxicity results after induction of EMT with TGF-β in transfected cells, but toxicity was less effective in hypoxia. The scratch test results also showed that cell movement was successfully prevented in EMT-transfected cells and thus confirmed EMT occlusion. Our findings indicate that by using structures containing diphtheria toxin downstream of a specific EMT promoter such as the N-cadherin promoter, the introduced toxin can kill specifically and block EMT in cancer cells.
Topics: Humans; A549 Cells; Antigens, CD; beta Catenin; Cadherins; Cell Movement; Diphtheria Toxin; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Genes, Transgenic, Suicide; Promoter Regions, Genetic; Vimentin
PubMed: 38822516
DOI: 10.18502/ijaai.v23i2.15327 -
Scientific Reports May 2024Globally dropout rate for the three dose of penta (DPT) vaccine was highest in the African region. This mainly occurred in the African Region including Ethiopia. Despite...
Globally dropout rate for the three dose of penta (DPT) vaccine was highest in the African region. This mainly occurred in the African Region including Ethiopia. Despite high national incomplete vaccination status, there is lack of study on the determinants of incomplete vaccination in south west region, Ethiopia. Therefore, this study was conducted to identify determinants of incomplete Penta vaccination among children aged 12 to 23 months in Mettu district South-West Ethiopia. A Community based case-control study was conducted from April 24, May 23, 2022 in South-west Ethiopia. Data was collected from 297 participants (99 cases and 198controls) by using simple random sampling techniques. Cases were children age from 9 to 23 months who missed at least one dose from the routine vaccine and controls were completed the entire routine vaccine schedule. Data was entered to Epi-data version 3.1 and exported to SPSS version 23 for statistical analyses. Binary and multivariable logistic regression with a 95% CI and a p-value of < 0.05 was done to declare statistical significance. A total of 95 cases and 197 controls participated in the study. Rural residence [AOR: 3.9; 95% CI; (1.6, 9.4)], wealth indexes [AOR: 3.6; 95% CI; (1.8,7.0)], mothers unimmunized tetanus toxoid [AOR: 4.3; 95% CI; (2.1, 8.6)], postponed schedule [AOR: 4.6; 95% CI; (2.4, 8.8)], un satisfied to service [AOR: 3.7; 95% CI; (1.7,7.6)] and poor perception on benefit of vaccine [AOR:2.7; 95% CI; (1.2, 6.1)] were determinants of incomplete vaccination. Rural Residence, Family wealth index of poor; Mother not received tetanus vaccination; postponed vaccination schedule client satisfaction and caretaker perception on benefit of vaccination were identified determinants of incomplete vaccination.Health information should be given for the community and child caretaker on the benefit of complete vaccination. Community should be encouraged to not post pond vaccine schedule. Pregnant women should be strengthening to receive tetanus toxoid vaccine during pregnancy.
Topics: Humans; Ethiopia; Female; Male; Infant; Vaccination; Case-Control Studies; Diphtheria-Tetanus-Pertussis Vaccine; Adult; Immunization Schedule; Vaccination Coverage
PubMed: 38821964
DOI: 10.1038/s41598-024-62153-5 -
ACS Infectious Diseases Jun 2024is a fungus classified by the World Health Organization as a critically important pathogen, which poses a significant threat to immunocompromised individuals. In this...
is a fungus classified by the World Health Organization as a critically important pathogen, which poses a significant threat to immunocompromised individuals. In this study, we present the chemical synthesis and evaluation of two semisynthetic vaccine candidates targeting the capsular polysaccharide glucuronoxylomannan (GXM) of . These semisynthetic glycoconjugate vaccines contain an identical synthetic decasaccharide (M2 motif) antigen. This antigen is present in serotype A strains, which constitute 95% of the clinical cryptococcosis cases. This synthetic oligosaccharide was conjugated to two proteins (CRM197 and Anthrax 63 kDa PA) and tested for immunogenicity in mice. The conjugates elicited a specific antibody response that bound to the M2 motif but also exhibited additional cross-reactivity toward M1 and M4 GXM motifs. Both glycoconjugates produced antibodies that bound to GXM in ELISA assays and to live fungal cells. Mice immunized with the CRM197 glycoconjugate produced weakly opsonic antibodies and displayed trends toward increased median survival relative to mice given a mock PBS injection (18 vs 15 days, = 0.06). These findings indicate promise, achieving a successful vaccine demands further optimization of the glycoconjugate. This antigen could serve as a component in a multivalent GXM motif vaccine.
Topics: Cryptococcus neoformans; Animals; Fungal Vaccines; Mice; Cryptococcosis; Glycoconjugates; Vaccines, Conjugate; Antibodies, Fungal; Female; Polysaccharides; Mice, Inbred BALB C; Bacterial Proteins; Antigens, Fungal
PubMed: 38819951
DOI: 10.1021/acsinfecdis.4c00094 -
Journal of Bacteriology Jun 2024is the causative agent of diphtheria, a severe respiratory disease in humans. colonizes the human upper respiratory tract, where it acquires zinc, an essential metal...
is the causative agent of diphtheria, a severe respiratory disease in humans. colonizes the human upper respiratory tract, where it acquires zinc, an essential metal required for survival in the host. While the mechanisms for zinc transport by are not well characterized, four putative zinc ABC-type transporter loci were recently identified in strain 1737: (), (), (), and (). A mutant deleted for all four loci (Δ4) exhibited similar growth to that of the wild-type strain in a zinc-limited medium, suggesting there are additional zinc transporters. Two additional gene loci predicted to be associated with metal import, () and () were deleted in the Δ4 mutant to construct a new mutant designated Δ6. The Δ6 mutant exhibited significantly reduced growth under zinc limitation relative to the wild type, suggesting a deficiency in zinc acquisition. Strains retaining the , , or loci grew to near-wild-type levels in the absence of the other five loci, indicating that each of these transporters may be involved in zinc uptake. Plasmid complementation with cloned , , , or loci also enhanced the growth of the Δ6 mutant. Quantification of intracellular zinc content by inductively coupled plasma mass spectrometry was consistent with reduced zinc uptake by Δ6 relative to the wild type and further supports a zinc uptake function for the transporters encoded by , , and . This study demonstrates that zinc transport is complex and involves multiple zinc uptake systems.IMPORTANCEZinc is a critical nutrient for all forms of life, including human bacterial pathogens. Thus, the tools that bacteria use to acquire zinc from host sources are crucial for pathogenesis. While potential candidates for zinc importers have been identified in from gene expression studies, to date, no study has clearly demonstrated this function for any of the putative transporters. We show that encodes at least six loci associated with zinc import, underscoring the extent of redundancy for zinc acquisition. Furthermore, we provide evidence that a previously studied manganese-regulated importer can also function in zinc import. This study builds upon our knowledge of bacterial zinc transport mechanisms and identifies potential targets for future diphtheria vaccine candidates.
Topics: Corynebacterium diphtheriae; Zinc; Bacterial Proteins; Gene Expression Regulation, Bacterial; Biological Transport; ATP-Binding Cassette Transporters; Humans
PubMed: 38809016
DOI: 10.1128/jb.00124-24 -
Bioelectronic Medicine May 2024Key to the advancement of the field of bioelectronic medicine is the identification of novel pathways of neural regulation of immune function. Sensory neurons (termed...
BACKGROUND
Key to the advancement of the field of bioelectronic medicine is the identification of novel pathways of neural regulation of immune function. Sensory neurons (termed nociceptors) recognize harmful stimuli and initiate a protective response by eliciting pain and defensive behavior. Nociceptors also interact with immune cells to regulate host defense and inflammatory responses. However, it is still unclear whether nociceptors participate in regulating primary IgG antibody responses to novel antigens.
METHODS
To understand the role of transient receptor potential vanilloid 1 (TRPV1)-expressing neurons in IgG responses, we generated TRPV1-Cre/Rosa-ChannelRhodopsin2 mice for precise optogenetic activation of TRPV1 + neurons and TRPV1-Cre/Lox-diphtheria toxin A mice for targeted ablation of TRPV1-expressing neurons. Antigen-specific antibody responses were longitudinally monitored for 28 days.
RESULTS
Here we show that TRPV1 expressing neurons are required to develop an antigen-specific immune response. We demonstrate that selective optogenetic stimulation of TRPV1 nociceptors during immunization significantly enhances primary IgG antibody responses to novel antigens. Further, mice rendered deficient in TRPV1- expressing nociceptors fail to develop primary IgG antibody responses to keyhole limpet hemocyanin or haptenated antigen.
CONCLUSION
This functional and genetic evidence indicates a critical role for nociceptor TRPV1 in antigen-specific primary antibody responses to novel antigens. These results also support consideration of potential therapeutic manipulation of nociceptor pathways using bioelectronic devices to enhance immune responses to foreign antigens.
PubMed: 38807193
DOI: 10.1186/s42234-024-00145-6 -
The American Journal of Tropical... May 2024Information on notifiable bacterial diseases (NBD) in low- and middle-income countries (LMICs) is frequently incomplete. We developed the AutoMated tool for the...
Information on notifiable bacterial diseases (NBD) in low- and middle-income countries (LMICs) is frequently incomplete. We developed the AutoMated tool for the Antimicrobial resistance Surveillance System plus (AMASSplus), which can support hospitals to analyze their microbiology and hospital data files automatically (in CSV or Excel format) and promptly generate antimicrobial resistance surveillance and NBD reports (in PDF and CSV formats). The NBD reports included the total number of cases and deaths after Brucella spp., Burkholderia pseudomallei, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Neisseria meningitidis, nontyphoidal Salmonella spp., Salmonella enterica serovar Paratyphi, Salmonella enterica serovar Typhi, Shigella spp., Streptococcus suis, and Vibrio spp. infections. We tested the tool in six hospitals in Thailand in 2022. The total number of deaths identified by the AMASSplus was higher than those reported to the national notifiable disease surveillance system (NNDSS); particularly for B. pseudomallei infection (134 versus 2 deaths). This tool could support the NNDSS in LMICs.
PubMed: 38806021
DOI: 10.4269/ajtmh.23-0848 -
Journal of Health Economics Jun 2024Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a... (Randomized Controlled Trial)
Randomized Controlled Trial
Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a substantial proportion of children remain unvaccinated. We revisit households 30 months after a randomised experiment of a health information intervention designed to educate mothers on the benefits of child vaccination in Uttar Pradesh, India. We find that the large short-term effects on the uptake of diphtheria-pertussis-tetanus and measles vaccination were sustained at 30 months, suggesting the intervention did not simply bring forward vaccinations. We apply causal forests and find that the intervention increased vaccination uptake, but that there was substantial variation in the magnitude of the estimated effects. We conclude that characterising those who benefited most and conversely those who benefited least provides policy-makers with insights on how the intervention worked, and how the targeting of households could be improved.
Topics: Humans; India; Mothers; Female; Infant; Diphtheria-Tetanus-Pertussis Vaccine; Health Education; Child, Preschool; Adult; Male; Vaccination; Immunization Programs; Measles Vaccine
PubMed: 38805881
DOI: 10.1016/j.jhealeco.2024.102899