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Search Results (2,254)

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15 pages, 1139 KiB  
Article
The Association Between the Dietary Inflammatory Index, Dietary Pattern, and Hypertension Among Residents in the Xinjiang Region
by Min Wang, Jiali Liao, Hao Wang, Lu Deng, Tingyu Zhang, Heng Guo, Xin Qian and Rulin Ma
Nutrients 2025, 17(1), 165; https://doi.org/10.3390/nu17010165 - 1 Jan 2025
Viewed by 593
Abstract
Background: Diet and inflammation are both associated with hypertension. We aimed to investigate the relationship between the dietary inflammation index (DII), dietary patterns, and the risk of hypertension among Xinjiang residents. Methods: A total of 930 residents aged 20–80 from Shihezi [...] Read more.
Background: Diet and inflammation are both associated with hypertension. We aimed to investigate the relationship between the dietary inflammation index (DII), dietary patterns, and the risk of hypertension among Xinjiang residents. Methods: A total of 930 residents aged 20–80 from Shihezi and Tumushuk were selected as participants using a stratified whole cluster random sampling method. General demographic information, dietary data, and physical examination results were collected from the participants and DII scores were calculated. Restricted cubic spline was used to analyze the dose–response relationship between the DII and the risk of hypertension. LASSO regression was used to screen dietary factors associated with hypertension. Factor analysis was used to extract dietary patterns. Finally, logistic regression modeling was used to analyze the association between the DII, dietary patterns, and the risk of hypertension. Results: The DII was linearly and positively associated with the risk of developing hypertension. Logistic regression analysis showed that the prevalence of hypertension was 2.23 (95% CI: 1.53, 3.23) and 3.29 (95% CI: 2.26, 4.79) in the T2 and T3 groups, respectively, compared with the T1 group. Riboflavin and folate were associated with the risk of hypertension. In the vegetable–egg dietary pattern, the risk of hypertension was reduced by 33%, 39%, and 37% in groups Q2, Q3, and Q4, respectively, compared with group Q1 (Q2: OR = 0.67, 95% CI: 0.45, 0.99; Q3: OR = 0.61, 95% CI: 0.41, 0.92; Q4: OR = 0.63, 95% CI: 0.42, 0.96). Conclusions: The higher the DII score, the higher the risk of hypertension among residents of Xinjiang. In addition, vegetable–egg dietary patterns can reduce the risk of hypertension. Therefore, local residents should be scientifically instructed to increase their intake of vegetables and eggs. Full article
(This article belongs to the Section Nutritional Immunology)
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<p>Flow chart of the study population.</p>
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<p>Restricted cubic spline curve of DII and the risk of hypertension.</p>
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<p>LASSO regression screening for key dietary factors associated with hypertension. (<b>a</b>) LASSO regression coefficient plots. (<b>b</b>) Cross-validation plots. LASSO regression, minimum absolute contraction, and selection operator.</p>
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<p>Development and validation of a predictive model for hypertension risk. (<b>a</b>) Column nomogram of key dietary factors associated with hypertension identified by LASSO regression. The green lines indicate the individual scores for each variable, and the blue lines indicate the risk of developing hypertension corresponding to the total score when the individual scores for both variables are added together. (<b>b</b>) ROC curves evaluating the predictive ability of the column-line graph model for hypertension. LASSO: least absolute shrinkage, and selection operator; ROC: receiver operator characteristic curve.</p>
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15 pages, 2474 KiB  
Article
Air Pollution and COPD: Unveiling Hidden Risks of Mortality, Mechanical Ventilation, and Prolonged Hospitalization
by Jovan Javorac, Dejan Živanović, Miroslav Ilić, Ana Milenković, Emilija Vujičić, Dragica Kovačević, Jelena Zvekić-Svorcan, Darko Mikić, Svetlana Stojkov, Jasminka Bačevac Eminović and Marija Jevtić
Atmosphere 2025, 16(1), 36; https://doi.org/10.3390/atmos16010036 - 1 Jan 2025
Viewed by 430
Abstract
While the impact of air pollution on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has been widely studied, its effect on hospitalization outcomes remains less explored. This study examines the influence of short-term air pollution exposure on adverse hospitalization outcomes—mortality, mechanical ventilation [...] Read more.
While the impact of air pollution on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has been widely studied, its effect on hospitalization outcomes remains less explored. This study examines the influence of short-term air pollution exposure on adverse hospitalization outcomes—mortality, mechanical ventilation use, and prolonged hospitalization—in patients with non-infectious severe AECOPD in Novi Sad, Serbia. Using a five-year time-series analysis, concentrations of selected air pollutants (PM10, PM2.5, SO2, and NO2) and meteorological data were integrated with hospitalization outcomes. Distributed lag non-linear models (DLNMs) revealed significant associations between rising air pollutant levels and some unfavorable outcomes. Exposure to rising PM2.5 (urban background) and SO2 (urban traffic) concentrations were linked to higher risks of mechanical ventilation (cumulative OR 21.95 (95% CI 1.07–449.45) and 11.37 (95% CI 1.25–103.27), respectively) and prolonged non-infectious AECOPD hospitalization (cumulative RR 2.27 (95% CI 1.14–4.52) and 2.24 (95% CI 1.38–3.64), respectively). No cumulative lag effects on mortality were observed, though specific patterns emerged in individual lag models. These findings highlight the critical role of improving air quality in reducing some COPD-related hospitalization risks. Full article
(This article belongs to the Special Issue Toxicology and Health Effects of Air Pollution)
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<p>The network of stations collecting data on meteorological parameters and air pollution within the territory of Novi Sad. Legend: 1—meteorological station (45°20′ N, 19°51′ E); 2,3—UB air pollution stations (45°14′ N, 19°50′ E and 45°25′ N, 19°85′ E); 4,5,6—UT air pollution stations (45°15′ N, 19°49′ E, 45°24′ N, 19°81′ E, and 45°25′ N, 19°83′ E).</p>
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<p>A time series of the average daily concentrations of selected air pollutants (PM<sub>10</sub>, PM<sub>2.5</sub>, SO<sub>2</sub>, and NO<sub>2</sub>) from the urban background environment (<b>a</b>) and urban traffic environment (<b>b</b>). Legend: the figure includes two lines: DPGV, represented by a red dashed line, which signifies the daily recommended concentrations of environmental air pollutants as outlined in Directive 2008/50/EC and the legal acts of the Republic of Serbia; and GPGV, represented by a dark red dashed line, which indicates the annual recommended concentrations of environmental air pollutants as specified in Directive 2008/50/EC and the legal acts of the Republic of Serbia.</p>
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<p>Lag effects of increasing NO<sub>2</sub>(UB) and PM<sub>2.5</sub>(UB) concentrations on the probability of fatal outcomes during AECOPD hospitalization (multi-predictor models). Legend: (<b>a</b>) NO<sub>2</sub>(UB) multi-predictor models—in lag0, there is no effect or a slight and statistically insignificant tendency towards a “protective” effect, which becomes more pronounced (increasing faster with higher concentrations) in later lag periods. From lag5 to lag7, there is a statistically significant effect of increasing the risk of fatal outcomes due to AECOPD; (<b>b</b>) PM<sub>2.5</sub>(UB) multi-predictor models—in lag0, the calculated OR is close to 1 (but not statistically significant), while in later lag periods, the OR values become lower than 1. A statistically significant “protective” effect is achieved in lag4 and lag5 for all concentrations, with a more pronounced effect observed at higher concentrations.</p>
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<p>Lag effects of SO<sub>2</sub>(UT) and PM<sub>2.5</sub>(UB) on the occurrence of AECOPD hospitalizations requiring the use of mechanical ventilation. Legend: (<b>a</b>) SO<sub>2</sub>(UT) single-predictor models—in lag0, the influence of the predictor on the criterion is “protective” for all concentrations, but it is not statistically significant. In lag1, there is no correlation, and in subsequent lags, the effect grows rapidly. Statistically significant effects of all predictor concentrations on the higher probability of using mechanical ventilation are present in lag4 and lag5; (<b>b</b>) PM<sub>2.5</sub>(UB) multi-predictor models—on this contour plot, it can be seen that all predictor concentrations in all lags have an OR that is above 1 (red color), which indicates an increased chance of the outcome occurring. The effects are more pronounced at higher concentrations and in later lags. A statistically significant elevated effect is present only in lag4.</p>
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<p>Lag effects of SO<sub>2</sub> on the RR for the prolonged duration of AECOPD hospitalizations (single-predictor models). Legend: (<b>a</b>) SO<sub>2</sub>(UB)—the effect of all predictor levels (different concentrations are marked by curves of different colors) is in the initial lags (lag0-lag3) as “protective” (RR less than 1, which would indicate a reduced duration of hospitalization), but these effects are not statistically significant. In lag3, the RR value for all predictor levels is 1, after which the RR value increases, more slowly at lower concentrations, and a stronger relationship exists at higher concentrations. The RR values for lag5-lag7 are statistically significant (exposure to all predictor concentrations prolongs the duration of hospitalization in these lags); (<b>b</b>) SO<sub>2</sub>(UT)—contour graph indicates that in lag0, the effect of increasing concentrations tends to be “protective” and more so at higher concentrations of SO<sub>2</sub>(UT), but nowhere is this effect statistically significant. At later lags, the RR value increases, more so at higher concentrations, and it becomes statistically significant (prolonged duration of AECOPD hospitalization) after lag3 for all concentrations (greater effect at higher concentrations).</p>
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12 pages, 3166 KiB  
Article
Trachemys scripta Eggs as Part of a Potential In Vivo Model for Studying Sea Turtle Egg Fusariosis
by María Martínez-Ríos, Laura Martín-Torrijos and Javier Diéguez-Uribeondo
J. Fungi 2025, 11(1), 23; https://doi.org/10.3390/jof11010023 - 1 Jan 2025
Viewed by 404
Abstract
The fungal pathogens Fusarium keratoplasticum and Fusarium falciforme are responsible for the emerging infectious disease named sea turtle egg fusariosis (STEF). This disease affects all sea turtle species throughout the world, causing low hatching success and mass mortalities. In this study, we investigated [...] Read more.
The fungal pathogens Fusarium keratoplasticum and Fusarium falciforme are responsible for the emerging infectious disease named sea turtle egg fusariosis (STEF). This disease affects all sea turtle species throughout the world, causing low hatching success and mass mortalities. In this study, we investigated the potential use of widely available and easy-to-handle eggs of the invasive alien red-eared slider turtle, Trachemys scripta, as part of an in vivo host model to improve our knowledge of the biological properties of the pathogens responsible of the STEF. Specifically, we performed in vivo experiments, in which T. scripta eggs were challenged with conidia of F. keratoplasticum isolated from diseased sea turtle eggs. We found that the pathogen could colonize and develop similar signs to those observed in nature and fulfill Koch’s postulates. The pathogen showed high virulence properties (e.g., high disease incidence, severity, and low hatching success) and its ability to modify the pH in both the egg surface and culture media, confirming previously described fungal pathogen models. These results support the use of T. scripta as an experimental in vivo host model for studying the biological characteristics of STEF, thus providing valuable insights into the mechanisms underlying the emergence of this fungal disease. Full article
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<p>Sampling area of <span class="html-italic">Trachemys scripta</span> nests, El Marjal de Almenara wetland, Castellón (Spain).</p>
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<p>Design of the experimental in vivo host model using eggs of <span class="html-italic">Trachemys scripta</span>. Real (<b>left</b>) and schematic (<b>right</b>) image of an experiment carried out in plastic boxes with sterile wet vermiculite as an incubating substrate. In each experiment, 15 eggs arranged in three columns were used (five eggs/row). Each row represents one type of treatment (left to right): (i) control 1, which contains eggs as they came from the sample collection; (ii) control 2, which contains washed eggs with distilled water to remove traces of clay from the surface; and (iii) washed and inoculated eggs with growing fungal inoculum of <span class="html-italic">Fusarium keratoplasticum</span>.</p>
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<p>Signs of sea turtle egg fusariosis on eggs of <span class="html-italic">Trachemys scripta</span>. (<b>A</b>–<b>C</b>) Infected eggs showing white fungal mycelium growth around the egg shell (arrow) (scale bar = 1 cm). (<b>B</b>,<b>D</b>–<b>F</b>) Infected eggs showing the gray spots (arrow) typically associated with this disease (scale bar = 1 cm).</p>
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<p>Non-infected eggs of <span class="html-italic">Trachemys scripta</span>. (<b>A</b>) An egg that shows no signs of fungal infection (scale bar = 1 cm). (<b>B</b>) Non-infected unhatched (left) and hatched (right) eggs (scale bar = 1 cm).</p>
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17 pages, 803 KiB  
Review
What Veterinarians Need to Know About the Newly-Emerging Field of Insects-as-Food-and-Feed
by Kimberly L. Boykin and Mark A. Mitchell
Vet. Sci. 2025, 12(1), 12; https://doi.org/10.3390/vetsci12010012 - 31 Dec 2024
Viewed by 473
Abstract
Over the last two decades, the insects-as-food-and-feed industry has rapidly emerged. Its growth is largely because insects require substantially less resources (water, food, and energy) to produce than traditional sources of animal protein, making it a sustainable alternative food option. As this industry [...] Read more.
Over the last two decades, the insects-as-food-and-feed industry has rapidly emerged. Its growth is largely because insects require substantially less resources (water, food, and energy) to produce than traditional sources of animal protein, making it a sustainable alternative food option. As this industry continues to grow, veterinarians will likely be called upon to assist in identifying food safety concerns, assessing animal health, implementing biosecurity measures, and formulating/prescribing treatment protocols comparable to what we have seen with the honeybee industry and the institution of veterinary feed directives (VFDs). Similar to other agricultural markets, high animal densities and management practices put insects at high risk for infectious diseases. Veterinarians interested in working with these species will need to become knowledgeable regarding the diseases afflicting the feeder insect industry and how best to diagnose and treat pathogens of concern. Using the edible cricket industry as an example, this review will highlight health and production issues while drawing similarities to other traditional livestock operations. If the insects-as-feed-and-food industry is going to be viable, veterinary involvement will be essential to ensure that insects can be used as a safe source of food for all. Full article
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<p>Visual representations of the top three cricket species used in the feeder insect industry, (<b>A</b>) <span class="html-italic">Acheta domesticus</span> cricket, adult female [<a href="#B40-vetsci-12-00012" class="html-bibr">40</a>]; (<b>B</b>) <span class="html-italic">Gryllodes sigillatus</span> cricket, subadult female [<a href="#B41-vetsci-12-00012" class="html-bibr">41</a>]; (<b>C</b>) <span class="html-italic">Gryllus assimilis</span> cricket, adult male [<a href="#B42-vetsci-12-00012" class="html-bibr">42</a>].</p>
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11 pages, 808 KiB  
Article
Antimicrobial Stewardship in the Pediatric Emergency Department: An Observational Pre-Post Study
by Erika Silvestro, Ilaria Mussinatto, Antonia Versace, Marco Denina, Giulia Pruccoli, Raffaella Marino, Giulia Mazzetti, Lorenzo Scaglione, Federico Vigna, Alessandra Macciotta, Silvia Garazzino and Claudia Bondone
Children 2025, 12(1), 46; https://doi.org/10.3390/children12010046 - 30 Dec 2024
Viewed by 342
Abstract
Background/Objectives: To face antimicrobial resistance, antimicrobial stewardship programs (ASPs) have been implemented in the pediatric age, but the area of urgency remains understudied. We aimed to assess the impact of an educational program on optimizing antibiotic appropriateness in a pediatric ED. Methods [...] Read more.
Background/Objectives: To face antimicrobial resistance, antimicrobial stewardship programs (ASPs) have been implemented in the pediatric age, but the area of urgency remains understudied. We aimed to assess the impact of an educational program on optimizing antibiotic appropriateness in a pediatric ED. Methods: We conducted a pre-post observational study with an audit, intervention, and feedback given to prescribers. We recorded all systemic antibiotic prescriptions for children attending our pediatric ED from January to March and from July to September 2020. The study’s team assigned a score to each prescription, regarding the appropriate molecule, dose, and duration of therapy, according to the diagnosis. From April to June 2020, we held weekly meetings focusing on different pediatric infectious diseases, with interaction between one to three ED physicians and the infectious disease (ID) specialist of the study’s team. We then distributed synthetic digital guidelines adapted to our reality to all prescribers. Results: Optimal antibiotic prescriptions increased after the intervention, with statistical significance (p < 0.001) in four main aspects (overall adequacy: 13% PRE vs. 43% POST; need of antibiotics: 53% vs. 68%; adequacy of the spectrum: 55% vs. 63%; adequacy of the chosen molecule: 54% vs. 62%). We observed an improvement in all the main infectious diseases and concerns all the ED physicians. The prescription of first-choice drugs increased in specific and common illnesses such as otitis and pharyngotonsillitis. Conclusions: An antimicrobial stewardship program is a relevant method for improving the appropriateness of antimicrobial use also in the complex setting of a pediatric ED. Full article
(This article belongs to the Section Pediatric Emergency Medicine & Intensive Care Medicine)
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<p>Common antibiotics used to treat pharyngotonsillitis and otitis media, pre–post comparison.</p>
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<p>Percentage of grade “A” (complete agreement with the prescription by the study team) for the item “overall prescription appropriateness” for the site of infection, pre-post comparison.</p>
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16 pages, 2295 KiB  
Review
Overview of Recent Advances in Canine Parvovirus Research: Current Status and Future Perspectives
by Hongzhuan Zhou, Kaidi Cui, Xia Su, Huanhuan Zhang, Bing Xiao, Songping Li and Bing Yang
Microorganisms 2025, 13(1), 47; https://doi.org/10.3390/microorganisms13010047 - 30 Dec 2024
Viewed by 520
Abstract
Canine parvovirus (CPV-2) was first identified in the late 1970s and has since become one of the most significant infectious agents affecting dogs. CPV-2 causes severe diseases such as hemorrhagic gastroenteritis and myocarditis, posing a major threat to canine health, particularly with a [...] Read more.
Canine parvovirus (CPV-2) was first identified in the late 1970s and has since become one of the most significant infectious agents affecting dogs. CPV-2 causes severe diseases such as hemorrhagic gastroenteritis and myocarditis, posing a major threat to canine health, particularly with a high mortality rate in puppies. It is globally recognized as a highly contagious and lethal pathogen. CPV is prone to rapid mutation, leading to the emergence of new variants. Despite widespread vaccination efforts, CPV remains one of the primary causes of acute gastroenteritis and death in young and juvenile dogs. Furthermore, the detection of CPV in swine populations has introduced additional challenges to its control. This review summarizes the current epidemiological status of CPV, highlighting recent advancements in diagnostic techniques and vaccine development. Additionally, it discusses the latest research on the pathogenesis of the virus and the development of antiviral agent research and proposes prevention and control suggestions for CPV under the One Health concept. In particular, there is a need to enhance surveillance of viral dynamics, accelerate the development of novel vaccines, and deepen the exploration of the underlying pathogenic mechanisms. This review aims to provide a scientific foundation for effective control of CPV and to guide future research directions. Full article
(This article belongs to the Special Issue Advances in Parvovirus Infection of Pets and Waterfowl)
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<p>Global distribution of canine parvovirus. The complete genome sequences of Canine Parvovirus (CPV) available in GenBank were analyzed using SnapGene (Version 5.1.5) and WPS Office (Version 12.1.0.16417). Different colors are used to represent various genotype types, with the intensity of the color reflecting the different genotype combinations within the same type. Different species are represented by corresponding animal images.</p>
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<p>CPV-infection-mediated apoptosis and virus-host-cell interactions. (i) CPV infection activates caspase-8 and caspase-12, leading to the accumulation of reactive oxygen species (ROS). This accumulation results in a decrease in mitochondrial membrane potential, which triggers the release of cytochrome c and activates caspase-9. Ultimately, both caspase-8 and caspase-9 collaboratively upregulate the expression of caspase-3, thereby inducing apoptosis. (ii) CPV binds to the TfR receptor, which facilitates its internalization via endocytic transport to the lysosome. Additionally, this interaction activates the EGFR (Y1086)/p27 and STAT3 (Y705)/cyclin D1 signaling axes, leading to cell cycle arrest. (iii) CPV entry into host cells induces DNA damage, which subsequently triggers cell cycle arrest and apoptosis. This process leads to an increase in nuclear membrane permeability, allowing the viral capsid to escape via a CRM1-independent nuclear export pathway. (iv) The CPV coat protein VP2 is able to increase its own stability by binding to CCT7. The chart is based on content or images compiled from the cited articles [<a href="#B42-microorganisms-13-00047" class="html-bibr">42</a>,<a href="#B43-microorganisms-13-00047" class="html-bibr">43</a>,<a href="#B44-microorganisms-13-00047" class="html-bibr">44</a>,<a href="#B45-microorganisms-13-00047" class="html-bibr">45</a>,<a href="#B46-microorganisms-13-00047" class="html-bibr">46</a>].</p>
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<p>Potential antiviral agents against CPV. The current research on antiviral agents is primarily focused on four main categories: interferon-based formulations, antibody-based therapies, chemical drugs, and other types of treatments. The insights are visually represented via the “iSlide” plugin downloaded from <a href="https://www.islide.cc" target="_blank">https://www.islide.cc</a> (accessed on 20 November 2024).</p>
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<p>Comprehensive prevention and control of CPV under the concept of “One Health”. By fostering interdisciplinary, intersectoral, and interdepartmental collaborations, new perspectives and strategies are offered for the effective management of CPV. The insights are visually represented using the “iSlide” plugin downloaded from <a href="https://www.islide.cc" target="_blank">https://www.islide.cc</a> (accessed on 20 November 2024).</p>
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<p>Potential future research directions for CPV. (i) Development of novel vaccines. (ii) Studies on the evolution, transmission, and pathogenesis of CPV. (iii) Research on antiviral drug development. (iv) Construction of new diagnostic platforms. (v) Real-time monitoring of viral infections. The insights are visually represented using the “iSlide” plugin downloaded from <a href="https://www.islide.cc" target="_blank">https://www.islide.cc</a> (accessed on 20 November 2024).</p>
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10 pages, 578 KiB  
Opinion
Immunobridging Trials: An Important Tool to Protect Vulnerable and Immunocompromised Patients Against Evolving Pathogens
by Pedro Cruz, Jie Min Lam, Jehad Abdalla, Samira Bell, Jola Bytyci, Tal Brosh-Nissimov, John Gill, Ghady Haidar, Michael Hoerger, Yasmin Maor, Antonio Pagliuca, Francois Raffi, Ffion Samuels, Dorry Segev, Yuxin Ying and Lennard Y. W. Lee
Vaccines 2025, 13(1), 19; https://doi.org/10.3390/vaccines13010019 - 29 Dec 2024
Viewed by 469
Abstract
Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer [...] Read more.
Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer the effectiveness of a new drug through a surrogate measure of efficacy. Recently, this method has also been employed to authorise novel drugs, such as COVID-19 vaccines, and this article explores the concepts behind immunobridging trials, their advantages, issues, and significance in the context of COVID-19 and other infectious diseases. Our goal is to improve awareness among clinicians, patient groups, regulators, and health leaders of the opportunities and issues of immunobridging, so that fewer patients are left without protection from infectious diseases, particularly from major pathogens that may emerge. Full article
(This article belongs to the Section Clinical Immunology)
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<p>Immunobridging paradigm.</p>
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<p>Phase 3b immunobridging trials accelerate drug update and approval, thus decreasing the timespan in which patients are unprotected against new variants.</p>
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48 pages, 6035 KiB  
Review
Uncovering the Mechanism of Action of Antiprotozoal Agents: A Survey on Photoaffinity Labeling Strategy
by Alessandro Giraudo, Cristiano Bolchi, Marco Pallavicini, Roberto Di Santo, Roberta Costi and Francesco Saccoliti
Pharmaceuticals 2025, 18(1), 28; https://doi.org/10.3390/ph18010028 - 28 Dec 2024
Viewed by 828
Abstract
Plasmodium, Leishmania, and Trypanosoma parasites are responsible for infectious diseases threatening millions of people worldwide. Despite more recent efforts devoted to the search for new antiprotozoal agents, efficacy, safety, and resistance issues still hinder the development of suited therapeutic options. The [...] Read more.
Plasmodium, Leishmania, and Trypanosoma parasites are responsible for infectious diseases threatening millions of people worldwide. Despite more recent efforts devoted to the search for new antiprotozoal agents, efficacy, safety, and resistance issues still hinder the development of suited therapeutic options. The lack of robustly validated targets and the complexity of parasite’s diseases have made phenotypic screening a preferential drug discovery strategy for the identification of new chemical entities. However, via this approach, no information on biological target(s) and mechanisms of action of compounds are provided. Among the target deconvolution strategies useful to fill this gap, photoaffinity labeling (PAL) has emerged as one of most suited to enable investigation in a complex cellular environment. More recently, PAL has been exploited to unravel the molecular basis of bioactive compounds’ function in live parasites, allowing elucidation of the mechanism of action of both approved drugs and new chemical entities. Besides highlighting new potential drug targets, PAL can provide valuable information on efficacy and liabilities of small molecules at the molecular level, which could be exploited to greatly facilitate the rational optimization of compounds in terms of potency and safety. In this review, we will report the most recent studies that have leveraged PAL to disclose the biological targets and mechanism of action of phenotypically active compounds targeting kinetoplastid diseases (i.e., human African trypanosomiasis, leishmaniasis, and Chagas disease) and malaria. Moreover, we will comment on potential perspectives that this innovative approach can provide in aiding the discovery and development of new antiprotozoal drugs. Full article
(This article belongs to the Special Issue Recent Advancements in the Development of Antiprotozoal Agents)
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Graphical abstract
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<p>Main structural and functional features of a photoaffinity probe.</p>
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<p>General PAL workflow (upper flow) and competition assay (lower flow) relying on in situ tagging, affinity purification, electrophoresis, and analytical analyses to disclose specific and non-specific binders of alkyne-based probes for target ID.</p>
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<p>Chemical structures of antichagasic drugs (i.e., benznidazole and nifurtimox) and chemical entities in development for CD (i.e., fexinidazole and DNDI-6148).</p>
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<p>Chemical structures of antileishmanial drugs (i.e., sodium stibogluconate, amphotericin B, miltefosine, meglumine antimonite, and paromycin) and chemical entities in development for VL (i.e., GSK3186899, LXE408, and GSK3494245).</p>
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<p>Chemical structures of anti-HAT drugs and acoziborole, the new chemical entity in development for HAT.</p>
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<p>Chemical structures of artemisinin and artemisin-based probes <b>1</b>–<b>4</b>.</p>
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<p>Chemical structures of chamuvarinin, B-THP-T derivative <b>5</b>, and related probes <b>6</b> and <b>7</b>.</p>
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<p>Chemical structures of compound <b>8</b> and probe <b>9</b>.</p>
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<p>Chemical structures of compound <b>10</b> and probes <b>6</b>, <b>7</b>, <b>11</b>, and <b>12</b>.</p>
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<p>Chemical structures of 17-AAG and 17-mADAG.</p>
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<p>Chemical structures of actinoallolide A and probe <b>13</b>.</p>
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<p>Structure of drugs employed in the treatment of Malaria.</p>
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<p>Structures of Artemisinin, Artesunate, probes <b>14</b>–<b>16</b>, and photoaffinity probe APP.</p>
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<p>Structures of chloroquine, mefloquine, and photoaffinity probes.</p>
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<p>Structure of plasmodione, PDOox, PDOred, PDO-BX, and probes <b>18</b>–<b>22</b>. Ox = oxidation in vivo.</p>
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<p>Structures of ACT-213615, ACT-186128, and ACT-460953.</p>
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<p>Structures of guttiferone A and AZC-GA.</p>
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<p>Structures of DDD01035881, probe <b>23</b>, and parent compound <b>24</b>.</p>
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<p>Structures of <b>25</b> and chemical probes <b>26</b>–<b>30</b>.</p>
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<p>Structures of BIX01294 and probe <b>31</b>.</p>
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<p>Alkaloid dioncophylline A and its probes <b>32</b>–<b>34</b>.</p>
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<p>Structures of albitiazolium and probe UA1936.</p>
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21 pages, 709 KiB  
Review
Evaluating the Potential of Herbal Extracts as Treatment in Immune Thrombocytopenia: A Review of Evidence and Limitations
by Russell W. Wiggins, Jihoo Woo, John Nicholas Cauba and Shizue Mito
Appl. Biosci. 2025, 4(1), 1; https://doi.org/10.3390/applbiosci4010001 - 27 Dec 2024
Viewed by 525
Abstract
Immune thrombocytopenia, formerly idiopathic thrombocytopenia purpura (ITP), is an autoimmune disease characterized by the depletion of platelets below 100,000/µL when other causes of thrombocytopenia have been ruled out. It is associated with several infectious pathologies, disease states, and as a known side effect [...] Read more.
Immune thrombocytopenia, formerly idiopathic thrombocytopenia purpura (ITP), is an autoimmune disease characterized by the depletion of platelets below 100,000/µL when other causes of thrombocytopenia have been ruled out. It is associated with several infectious pathologies, disease states, and as a known side effect and complication of several drugs and chemotherapies. Standard treatment calls for glucocorticoid-mediated immunosuppression, intravenous immunoglobin transfusion, platelet stimulation, platelet transfusion, and splenectomy in instances of chronic and severe disease. While standard treatments are often effective, some cases prove resistant, and more commonly, some patients are unable to tolerate standard treatment protocols or opt out of surgical intervention. In addition, second-line therapies can be unfeasibly expensive and are associated with side effects themselves. Therefore, for a subset of patients afflicted by immune thrombocytopenia, the exploration of alternative treatment methods is needed in order to ease their burden of disease. Emerging evidence suggests that plant-derived extracts, traditionally used in regions such as Asia and Africa to manage acute thrombocytopenia, hold promise as alternative or adjunctive therapies for the mentioned subset of patients. These natural compounds may provide a cost-effective and less invasive option, potentially bridging gaps in current treatment regimens. We propose these extracts may play a role in fulfilling this deficiency in current treatment protocols. With this review, we aim to characterize and compile evidence that various organic extracts and compounds may be utilized to improve outcomes in these patients. By highlighting their clinical relevance and potential for integration into ITP treatment protocols, this manuscript underscores the importance of expanding the alternative therapies for ITP to improve patient outcomes and reduce treatment burdens. Full article
(This article belongs to the Special Issue Plant Natural Compounds: From Discovery to Application)
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<p>General schematic of phytochemical’s anti-inflammatory activities in cytokine signaling, NF-kB and JAK-STAT pathway [<a href="#B71-applbiosci-04-00001" class="html-bibr">71</a>,<a href="#B72-applbiosci-04-00001" class="html-bibr">72</a>].</p>
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26 pages, 2640 KiB  
Review
Beyond Needles: Immunomodulatory Hydrogel-Guided Vaccine Delivery Systems
by Md Mohosin Rana, Cigdem Demirkaya and Hector De la Hoz Siegler
Gels 2025, 11(1), 7; https://doi.org/10.3390/gels11010007 - 26 Dec 2024
Viewed by 1028
Abstract
Vaccines are critical for combating infectious diseases, saving millions of lives worldwide each year. Effective immunization requires precise vaccine delivery to ensure proper antigen transport and robust immune activation. Traditional vaccine delivery systems, however, face significant challenges, including low immunogenicity and undesirable inflammatory [...] Read more.
Vaccines are critical for combating infectious diseases, saving millions of lives worldwide each year. Effective immunization requires precise vaccine delivery to ensure proper antigen transport and robust immune activation. Traditional vaccine delivery systems, however, face significant challenges, including low immunogenicity and undesirable inflammatory reactions, limiting their efficiency. Encapsulating or binding vaccines within biomaterials has emerged as a promising strategy to overcome these limitations. Among biomaterials, hydrogels have gained considerable attention for their biocompatibility, ability to interact with biological systems, and potential to modulate immune responses. Hydrogels offer a materials science-driven approach for targeted vaccine delivery, addressing the shortcomings of conventional methods while enhancing vaccine efficacy. This review examines the potential of hydrogel-based systems to improve immunogenicity and explores their dual role as immunomodulatory adjuvants. Innovative delivery methods, such as microneedles, patches, and inhalable systems, are discussed as minimally invasive alternatives to traditional administration routes. Additionally, this review addresses critical challenges, including safety, scalability, and regulatory considerations, offering insights into hydrogel-guided strategies for eliciting targeted immune responses and advancing global immunization efforts. Full article
(This article belongs to the Special Issue Recent Advances in Microgels)
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<p>Adjuvants mediate their effects through mechanisms such as PRR activation, inflammasome-induced secretion of IL-1β and IL-18, and modulation of MHC antigen presentation. Some adjuvants may employ multiple pathways, including enhancing antigen uptake, PRR signaling, and immune cell recruitment. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>, <a href="https://BioRender.com/m49n412" target="_blank">https://BioRender.com/m49n412</a> (accessed on 23 December 2024).</p>
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<p>Illustration of immune cell dynamics upon hydrogel implantation, highlighting the recruitment of neutrophils during the first 48 h, followed by monocyte infiltration and differentiation into macrophages. Macrophage polarization into M1 (pro-inflammatory) or M2 (anti-inflammatory and reparative) phenotypes regulates inflammation and potential immunomodulation. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>, <a href="https://BioRender.com/i53p251" target="_blank">https://BioRender.com/i53p251</a> (accessed on 23 December 2024).</p>
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<p>Overview of respiratory mucosal immune components: Waldeyer’s ring (green), lymph nodes (blue) for systemic IgG responses, and ectopic tissues (red) like NALT and BALT for IgA production. (<b>A</b>) Dimeric IgA production in mucosal sites (BALT and NALT) facilitates immune exclusion by expelling antigens and involving pIgR-dependent secretory IgM and IgD (<b>B</b>). Reproduced with permission from Heida et al., 2022 [<a href="#B142-gels-11-00007" class="html-bibr">142</a>].</p>
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<p>Preparation and application of double-layered MNP: (<b>A</b>) nano-vaccine with HAP and melanoma peptides, (<b>B</b>) mold-cast double-layered MNP, and (<b>C</b>) dual-function MNP for anti-tumor and regenerative melanoma treatment. Reproduced with permission from Chen et al. (2024) [<a href="#B149-gels-11-00007" class="html-bibr">149</a>].</p>
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17 pages, 1431 KiB  
Article
Assessment of the Knowledge, Attitude, and Perception (KAP) of Sheep Farmers Regarding Ticks and Tick-Borne Pathogens in Tunisia, North Africa
by Médiha Khamassi Khbou, Syrine Rekik, Rihab Romdhane, Limam Sassi, Felicitas Bergmann, Martin H. Groschup, Mourad Rekik and Mohamed Gharbi
Vet. Sci. 2025, 12(1), 2; https://doi.org/10.3390/vetsci12010002 - 26 Dec 2024
Viewed by 611
Abstract
Ticks and tick-borne pathogens (TBPs) are a threat to human and animal health worldwide. A structured questionnaire was used to assess the knowledge, attitudes/practices, and perceptions (KAP) of 86 farmers of extensive sheep farming systems across different agro-ecological areas in Tunisia. The response [...] Read more.
Ticks and tick-borne pathogens (TBPs) are a threat to human and animal health worldwide. A structured questionnaire was used to assess the knowledge, attitudes/practices, and perceptions (KAP) of 86 farmers of extensive sheep farming systems across different agro-ecological areas in Tunisia. The response rate was about 91.3%. Overall, 68.5% of the questions referring to knowledge and perceptions were answered correctly. Indeed, about half of the respondents were aware that ticks infest animals, with weight loss given as the major consequence. However, more than half of the farmers were unaware of the transmission and vectorial role of ticks. Those who knew that ticks are vectors cited microbes and icterus as the main concerns. A broad majority of farmers (70.9%) stated that they removed the attached ticks manually and 45.3% crushed them. As acaricides were perceived to be efficient for fighting ticks, according to 97.7% of the sheep farmers, they were used for both the animals and their sleeping areas. Although the toxicity of acaricides is known, 59.3% of the respondents did not use personal protection equipment when applying these products. Taken together, gaps in KAP among sheep farmers were identified. It can be used to better design awareness communication tools for TBPs. Full article
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<p>Map of Tunisia, showing in red dots the localities where sheep owners were interviewed [<a href="#B12-vetsci-12-00002" class="html-bibr">12</a>].</p>
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<p>Classification of sheep farmers’ knowledge and perceptions regarding ticks and tick-borne pathogens (the answers are given as percentages among the total answers given for all the knowledge and perception questions). Answers related to knowledge and perception questions were classified as correct or incorrect according to the state of the art.</p>
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<p>Classification of sheep farmers’ attitudes and practices regarding ticks and tick-borne pathogens (the answers are given as percentages among the total answers given for all the attitudes and practices questions). Negative attitude was defined as dangerous and/or incorrect behaviour, and positive attitude is defined as not harmful and/or protective behaviour.</p>
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<p>Proportions of correct and incorrect answers to knowledge and perception questions (the answers are given as percentages among the total answers given for each question related to the farmers’ knowledge and perception). All questions with the corresponding answers are provided in <a href="#app1-vetsci-12-00002" class="html-app">Supplementary Table S1</a>.</p>
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<p>“Positive” and “negative” answers to attitudes and practice questions (the answers are given as percentages among the total answers given for each question related to the farmers’ practices and attitudes). All questions with the corresponding answers are provided in <a href="#app1-vetsci-12-00002" class="html-app">Supplementary Table S1</a>.</p>
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14 pages, 4428 KiB  
Article
Development of 111In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT
by Takeshi Fuchigami, Mya Myat Ngwe Tun, Yusuke Tanahara, Kodai Nishi, Sakura Yoshida, Kazuma Ogawa, Morio Nakayama and Daisuke Hayasaka
Molecules 2025, 30(1), 38; https://doi.org/10.3390/molecules30010038 - 26 Dec 2024
Viewed by 353
Abstract
No effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of 111In-labeled anti-SFTSV antibodies targeting SFTSV structural proteins as single-photon emission [...] Read more.
No effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of 111In-labeled anti-SFTSV antibodies targeting SFTSV structural proteins as single-photon emission computed tomography (SPECT) imaging agents for the selective visualization of SFTSV-infected sites. This study used nuclear medicine imaging to elucidate the pathology of SFTS and assess its therapeutic efficacy. Immunostaining experiments confirmed that the anti-SFTSV antibody (N-mAb), which targets the N protein, specifically accumulated in SFTSV-infected Vero E6 cells. 111In-labeled N-mAb was successfully prepared using a diethylenetriaminepentaacetic acid (DTPA) chelator, resulting in [111In]In-DTPA-N-mAb with high radiochemical purity exceeding 95% and a radiochemical yield of 55%. Cell-binding assays using SFTSV-infected Vero E6 cells demonstrated that [111In]In-DTPA-N-mAb binding was detectable even without membrane permeabilization, with the binding intensity correlating with infection levels. In vivo studies using SFTSV-infected A129 mice showed high spleen accumulation of [111In]In-DTPA-N-mAb (87.5% ID/g), consistent with SFTSV tropism, compared to 12.3% ID/g in mock-infected mice. SPECT/CT imaging clearly revealed high radioactivity in these regions. Although nonspecific accumulation was noted in the liver and spleen, this issue may be mitigated through antibody modifications such as fragmentation or PEGylation. Overall, [111In]In-DTPA-N-mAb is a promising imaging agent for non-invasive visualization of SFTSV-infected sites and may aid in elucidating SFTS pathology and assessing therapeutic efficacy. Full article
(This article belongs to the Special Issue New Insights into Radiopharmaceuticals)
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<p>Fluorescence images of the SFTSV antibody targeting N protein (Primary Ab: 4A10) (<b>A</b>), Gn protein (2D4) (<b>B</b>), and Gc protein (3B4) (<b>C</b>) in Vero E6 cells infected with SFTSV at mock-infected or multiplicity of infection (MOI)-0.1. The secondary antibody was FITC-conjugated anti-mouse IgG (green), and DAPI was used for nuclear staining (blue). Scale bar = 100 µm.</p>
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<p>In vitro binding of <sup>111</sup>In-labeled IgG ([<sup>111</sup>In]In-DTPA-cIgG, [<sup>111</sup>In]In-DTPA-N-mAb) in SFTSV-infected (MOI-0.01, MOI-0.1) and mock-infected Vero E6 cells. Vero E6 cells were processed as only fixation (<b>A</b>) or fixation and permeabilization (<b>B</b>). ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001 (two-way ANOVA with Tukey’s post hoc test). Values are mean ± SEM, n = 5–10.</p>
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<p>Biodistribution of [<sup>111</sup>In]In-DTPA-N-mAb in mock- or SFTSV-infected (3 days p.i.) A129 mice. [<sup>111</sup>In]In-DTPA-N-mAb was injected intravenously via the tail vein into the mock- or SFTSV- infected mice. To evaluate the biodistribution, after 24 h the mice were sacrificed, and the organs were dissected. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001 for mock-infected mice vs. SFTSV-infected mice (multiple unpaired <span class="html-italic">t</span>-test). Data are represented as the percentage of injected dose (%ID)/g ± SD (n = 5–6).</p>
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<p>Representative axial (left panels), coronal (middle panels), and sagittal (right panels) SPECT/CT images of mock-infected (<b>A</b>) and SFTSV-infected (<b>B</b>) A129 mice 3 days after infection. SPECT/CT images were acquired 24 h after intravenous injection of [<sup>111</sup>In]In-DTPA-N-mAb. The arrows indicate the liver (yellow), spleen (red), and gastrointestinal tract (green).</p>
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<p>Analysis of the SPECT/CT images of [<sup>111</sup>In]In-DTPA-N-mAb in SFTSV-infected mouse using the CPR method. The cross-sectional image (<b>A</b>) was reconstructed along the red line in the SFTSV-infected mouse SPECT/CT imaging data (<b>B</b>).</p>
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<p>Preparation of [<sup>111</sup>In]In-DTPA-cIgG and [<sup>111</sup>In]In-DTPA-N-mAb.</p>
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14 pages, 3107 KiB  
Article
IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury
by Easmin Begum, Md Rashel Mahmod, Md Mahbobur Rahman, Fumiko Fukuma, Takeshi Urano and Yuki Fujita
Biomolecules 2025, 15(1), 16; https://doi.org/10.3390/biom15010016 - 26 Dec 2024
Viewed by 376
Abstract
The prognosis of spinal cord injury (SCI) is closely linked to secondary injury processes, predominantly driven by neuroinflammation. Interleukin-18 (IL-18) plays a pivotal role in this inflammatory response. In previous work, we developed an anti-IL-18 antibody capable of neutralizing the active form of [...] Read more.
The prognosis of spinal cord injury (SCI) is closely linked to secondary injury processes, predominantly driven by neuroinflammation. Interleukin-18 (IL-18) plays a pivotal role in this inflammatory response. In previous work, we developed an anti-IL-18 antibody capable of neutralizing the active form of IL-18. This study evaluated the functional effects of this antibody in a mouse model of SCI. IL-18 expression was significantly upregulated in the spinal cord following injury. In a mouse model of SCI (C57BL/6J strain), mice were administered 150 μg of the anti-IL-18 antibody intraperitoneally. IL-18 inhibition via antibody treatment facilitated motor functional recovery post-injury. This intervention reduced neuronal death, reactive gliosis, microglia/macrophage activation, and neutrophil infiltration. Additionally, IL-18 inhibition lowered the expression of pro-inflammatory factors, such as IL-1β and the M1 microglia/macrophage marker Ccl17, while enhancing the expression of the M2 microglia/macrophage marker Arginase 1. Collectively, our findings demonstrate that IL-18 inhibition promotes motor recovery and facilitates the polarization of M1 microglia/macrophages to the M2 phenotype, thereby fostering a neuroprotective immune microenvironment in mice with SCI. Full article
(This article belongs to the Section Cellular Biochemistry)
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<p>Changes in IL-18 expression following SCI. (<b>A</b>) IL-18 expression levels in the spinal cord 7 days after SCI. Relative IL-18 mRNA levels were quantified using real-time PCR and normalized to GAPDH. Data are presented as the mean ± SE from three independent experiments (<span class="html-italic">n</span> = 10). Results are shown as fold changes compared to sham mice. * <span class="html-italic">p</span> &lt; 0.05; analysis of variance (ANOVA) with Welch’s <span class="html-italic">t</span>-test. (<b>B</b>) Distribution of IL-18 (green) in the spinal cord 3 days after SCI. (<b>C</b>) IL-18 signal intensity as shown in (<b>B</b>). DAPI (cyan) was used for nuclear staining. Scale bar, 50 μm. SCI: spinal cord injury; GAPDH: glyceraldehyde 3-phosphate.</p>
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<p>Inhibition of IL-18 improves recovery of motor function following SCI. (<b>A</b>) Experimental schedule. (<b>B</b>) BMS scores were significantly higher in IL-18 antibody-treated mice compared to control antibody-treated mice. (<b>C</b>) IL-18 antibody treatment reduced errors in the ladder walk test. (<b>D</b>) No significant difference was observed in the rotarod test. Results are presented as mean ± SE (<span class="html-italic">n</span> = 12 per group). * <span class="html-italic">p</span> &lt; 0.05; two-way repeated-measures ANOVA with Sidak’s multiple comparisons test. SCI: spinal cord injury; BMS: Basso Mouse Scale; N.S.: not significant.</p>
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<p>Inhibition of IL-18 ameliorates the death of NeuN-positive neurons following SCI. (<b>A</b>) Representative images of immunohistochemical staining of neuronal cell death in the gray matter following SCI. Neurons were immunostained with an anti-NeuN antibody (red), and apoptotic cells were detected using an anti-cleaved caspase-3 (CC3) antibody (green). Scale bar: 50 μm. (<b>B</b>) Quantification of NeuN- and CC3-positive cells in the gray matter 2 mm rostral to the lesion epicenter, 7 days after SCI. Results are mean ± SE of five mice per group. * <span class="html-italic">p</span> &lt; 0.05; ANOVA with Tukey’s multiple comparisons test. Scale bar: 50 μm. SCI: spinal cord injury; NeuN: neuronal nuclei; CC3: cleaved caspase-3.</p>
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<p>Treatment of IL-18 antibody alleviates reactive gliosis. (<b>A</b>) Representative images of GFAP-positive cells (red) labeled with immunofluorescence 3 days after SCI. (<b>B</b>) Quantification of GFAP immunoreactivity in a 200× magnification field. Results are mean ± SE of five mice per group. * <span class="html-italic">p</span> &lt; 0.05; ANOVA with Tukey’s multiple comparisons test. Scale bar: 50 μm. SCI: spinal cord injury; GFAP: glial fibrillary acidic protein.</p>
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<p>Inhibition of IL-18 attenuates microglia/macrophage activation. (<b>A</b>) Representative images of Iba1-positive cells (red) labeled with immunofluorescence 3 days after SCI. (<b>B</b>) Quantification of Iba1-positive cells in a 200× magnification field. Results are mean ± SE of five mice per group. * <span class="html-italic">p</span> &lt; 0.05; ANOVA with Tukey’s multiple comparisons test. Scale bar: 50 μm. SCI: spinal cord injury; Iba1: ionized calcium-binding adapter molecule 1.</p>
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<p>Inhibition of IL-18 attenuates the pro-inflammatory (M1) response and increases the anti-inflammatory (M2) response. (<b>A</b>) IL-18 antibody reduces pro-inflammatory cytokine levels and the M1 microglia/macrophage marker. Relative mRNA expression levels of IL-1β and Ccl17 in the spinal cord 3 days after SCI were measured by qPCR. (<b>B</b>) IL-18 antibody increases anti-inflammatory cytokine levels and the M2 microglia/macrophage marker. Relative mRNA expression levels of Arg1 in the spinal cord 3 days after SCI were measured by qPCR. All data are presented as mean ± SE, <span class="html-italic">n</span> = 4. * <span class="html-italic">p</span> &lt; 0.05; ANOVA with Dunnett’s multiple comparisons tests. SCI: spinal cord injury; Arg1: arginase1; GAPDH: glyceraldehyde 3-phosphate.</p>
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<p>Cytokine/chemokine expression in the spinal cord of IL-18 antibody-treated mice. Pro-inflammatory cytokine levels, including TNF-α and CXCL1, showed a decreasing trend in IL-18 antibody-treated mice compared to control-treated mice.</p>
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22 pages, 2121 KiB  
Review
Decoding NAD+ Metabolism in COVID-19: Implications for Immune Modulation and Therapy
by Shixu Song, Jialing Gan, Qiuyue Long, Zhancheng Gao and Yali Zheng
Vaccines 2025, 13(1), 1; https://doi.org/10.3390/vaccines13010001 - 24 Dec 2024
Viewed by 471
Abstract
The persistent threat of COVID-19, particularly with the emergence of new variants, underscores the urgency for innovative therapeutic strategies beyond conventional antiviral treatments. Current immunotherapies, including IL-6/IL-6R monoclonal antibodies and JAK inhibitors, exhibit suboptimal efficacy, necessitating alternative approaches. Our review delves into the [...] Read more.
The persistent threat of COVID-19, particularly with the emergence of new variants, underscores the urgency for innovative therapeutic strategies beyond conventional antiviral treatments. Current immunotherapies, including IL-6/IL-6R monoclonal antibodies and JAK inhibitors, exhibit suboptimal efficacy, necessitating alternative approaches. Our review delves into the significance of NAD+ metabolism in COVID-19 pathology, marked by decreased NAD+ levels and upregulated NAD+-consuming enzymes such as CD38 and poly (ADP-ribose) polymerases (PARPs). Recognizing NAD+’s pivotal role in energy metabolism and immune modulation, we propose modulating NAD+ homeostasis could bolster the host’s defensive capabilities against the virus. The article reviews the scientific rationale behind targeting NAD+ pathways for therapeutic benefit, utilizing strategies such as NAD+ precursor supplementation and enzyme inhibition to modulate immune function. While preliminary data are encouraging, the challenge lies in optimizing these interventions for clinical use. Future research should aim to unravel the intricate roles of key metabolites and enzymes in NAD+ metabolism and to elucidate their specific mechanisms of action. This will be essential for developing targeted NAD+ therapies, potentially transforming the management of COVID-19 and setting a precedent for addressing other infectious diseases. Full article
(This article belongs to the Special Issue Next-Generation Vaccine and Immunotherapy)
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<p><b>Overview of NAD+ biosynthesis and degradation pathways.</b> The upper panel presents three pathways involved in NAD+ biosynthesis: the de novo pathway, the Preiss-Handler pathway, and the salvage pathway. In the de novo pathway, tryptophan (Trp) is converted into quinolinic acid (QA), which is processed into nicotinic acid mononucleotide (NAMN) by QPRT, eventually leading to NAD+ synthesis. The Preiss-Handler pathway converts nicotinic acid (NA) into NAMN through NAPRT, with subsequent conversion into NAD+ via NMNAT and NADS enzymes. The salvage pathway involves nicotinamide riboside (NR) being converted to nicotinamide mononucleotide (NMN) by NRK, which is then transformed into NAD+ by NMNAT. The lower panel illustrates the degradation and utilization of NAD+ by enzymes like sirtuins (SIRTs), poly (ADP-ribose) polymerases (PARPs), and CD38. These enzymes regulate diverse cellular processes such as epigenetic modifications, DNA repair, immune response, and calcium signaling. NAD+ is hydrolyzed by these enzymes, producing nicotinamide (NAM) as a by-product, which can be recycled back into the salvage pathway via NAMPT.</p>
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<p><b>Impact of changes in NAD+ metabolism on the immune response in COVID-19 infection.</b> Upon entry of SARS-CoV-2 into host cells via the ACE2 receptor, the viral infection induces DNA damage that activates PARPs, leading to increased NAD+ consumption and further cellular damage, thereby compromising immune cell resilience. This NAD+ depletion reduces SIRT activity, impairing its anti-inflammatory regulatory function and triggering a surge of cytokines and chemokines that disrupt the innate immune balance. Concurrently, upregulation of CD38 expression exacerbates NAD+ depletion, promoting inflammation through calcium signaling to enhance innate immunity while converting extracellular NAD+ into adenosine, suppressing adaptive immune responses.</p>
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<p><b>CD38 and immune checkpoint expression patterns in T cell subsets of COVID-19 patients:</b> (<b>A</b>) Expression of CD38 and FOXP3 in different T cell subsets. (<b>B</b>) Expression of immune checkpoint molecules in different T cell subsets.</p>
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16 pages, 1065 KiB  
Review
Current Insights into Porcine Bocavirus (PBoV) and Its Impact on the Economy and Public Health
by Jelena Prpić, Tomislav Keros, Margarita Božiković, Magda Kamber and Lorena Jemeršić
Vet. Sci. 2024, 11(12), 677; https://doi.org/10.3390/vetsci11120677 - 22 Dec 2024
Viewed by 460
Abstract
Effective control of animal infectious diseases is crucial for maintaining robust livestock production systems worldwide. Porcine meat constitutes approximately 35–40% of global meat production with the largest producers being China and the European Union (EU). Emerging viral pathogens in swine, like porcine bocavirus [...] Read more.
Effective control of animal infectious diseases is crucial for maintaining robust livestock production systems worldwide. Porcine meat constitutes approximately 35–40% of global meat production with the largest producers being China and the European Union (EU). Emerging viral pathogens in swine, like porcine bocavirus (PBoV), have not garnered significant attention, leaving their pathogenic characteristics largely unexplored. This review aims to bridge this knowledge gap by conducting a comprehensive analysis of the existing literature on PBoV. We explore the virus’s genome structure, discovery, classification, detection methods, pathogenesis, and its potential public health implications. Additionally, we discuss the distribution and economic impact of PBoV, which includes potential losses due to decreased productivity, increased veterinary costs, and trade restrictions. By highlighting the current state of knowledge, this review seeks to enhance the understanding of PBoV, thereby aiding in its prevention and control, and mitigating its economic impact on the swine industry. Full article
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<p>Geographical distribution of PBoV. Map is created with Mapchart [<a href="#B36-vetsci-11-00677" class="html-bibr">36</a>].</p>
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<p>Phylogenetic tree of PBoV and related viruses based on the complete genome sequences. The tree was constructed using the Neighbor-Joining method with 1000 bootstrap replicates. Bootstrap values greater than 50% are shown at the branch nodes. The tree includes various BoV strains from different hosts, including humans, pigs, dogs, cats, cows, and gorillas. The scale bar represents the number of nucleotide substitutions per site. The phylogenetic tree reveals the relationships between PBoV and other bocaviruses. Notably, PBoV is closely related to other bocaviruses, including feline bocavirus and bovine bocavirus.</p>
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<p>The genome structure of PBoV (adapted from [<a href="#B71-vetsci-11-00677" class="html-bibr">71</a>]). The PBoV genome of approximately 5.3 bb contains three ORFs that encode for four proteins (NS1, NP1, VP1, and VP2).</p>
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