Search Results (1,126)

Streptococcus pyogenes (Group A Streptococcus, StrepA) is a human pathogen responsible for hundreds of millions of infections each year and remains one of the most prevalent bacterial causes of upper respiratory and skin infections worldwide. Despite its global impact, there is no approved vaccine, and the optimal protective immune response is still not fully understood. In particular, the role of Th17 T cells in immunity against StrepA remains to be explored. We have previously shown that Th17 T cells are induced in humans following StrepA infection. In this study, we investigated the role of Th17 T cells during skin and upper airway StrepA infections. To generate StrepA-specific Th17 T cells, we utilized a novel cationic liposomal adjuvant system. We demonstrated that vaccine-induced Th17 T cells are recruited to the skin and upper airways upon StrepA infection. In the airways, Th17 T cells and IgA correlate with protection, whereas Th1 T cells and IgG do not. To further characterize the recruited Th17 T cells, we used an IL-17 fate-reporter mouse model to track Th17 T cells. Our results show that Th17 T cells outnumber bona fide Th1 T cells in both StrepA-infected skin and upper airways. Surprisingly, most Th17 T cells lose expression of IL-17, and do not express TNFα, IFNγ, and IL-2. Initial single-cell sequencing data suggest the existence of multiple Th17 T cell subsets with distinct expression profiles. We discuss the functional relevance of these subsets in the context of a StrepA infection. Full article

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects motor neurons, leading to loss of muscle control, and, ultimately, respiratory failure and death. Despite some advances in recent years, the underlying genetic and molecular mechanisms of ALS remain largely elusive. In this respect, a better understanding of these mechanisms is needed to identify new and biologically relevant therapeutic targets that could be developed into treatments that are truly disease-modifying, in that they address the underlying causes rather than the symptoms of ALS. In this study, we used two approaches to model multi-omics data in order to map and elucidate the genetic and molecular mechanisms involved in ALS, i.e., the molecular landscape building approach and the Patrimony platform. These two methods are complementary because they rely upon different omics data sets, analytic methods, and scoring systems to identify and rank therapeutic target candidates. The orthogonal combination of the two modeling approaches led to significant convergences, as well as some complementarity, both for validating existing therapeutic targets and identifying novel targets. As for validating existing targets, we found that, out of 217 different targets that have been or are being investigated for drug development, 10 have high scores in both the landscape and Patrimony models, suggesting that they are highly relevant for ALS. Moreover, through both models, we identified or corroborated novel putative drug targets for ALS. A notable example of such a target is MATR3, a protein that has strong genetic, molecular, and functional links with ALS pathology. In conclusion, by using two distinct and highly complementary disease modeling approaches, this study enhances our understanding of ALS pathogenesis and provides a framework for prioritizing new therapeutic targets. Moreover, our findings underscore the potential of leveraging multi-omics analyses to improve target discovery and accelerate the development of effective treatments for ALS, and potentially other related complex human diseases. Full article

Molds readily grow on wet books, documents, and other library materials where they ruin them chemically, mechanically, and aesthetically. Poor maintenance of libraries, failures of Heating, Ventilation, and Air Conditioning (HVAC) systems, roof leaks, and storm damage leading to flooding can all result in accelerated fungal growth. Moreover, when fungal spores are present at high concentrations in the air, they can be linked to severe respiratory conditions and possibly to other adverse health effects in humans. Climate change and the accompanying storms and floods are making the dual potential of fungi to biodegrade library holdings and harm human health more common. This essay is intended for microbiologists without much background in mycology who are called in to help librarians who are dealing with mold outbreaks in libraries. Our goal is to demystify aspects of fungal taxonomy, morphology, and nomenclature while also recommending guidelines for minimizing mold contamination in library collections. Full article

Nipah virus (NiV) and Hendra virus (HeV), which both belong to the genus henipavirus, are zoonotic pathogens that cause severe systemic, neurological, and/or respiratory disease in humans and a variety of mammals. Therefore, monitoring viral prevalence in natural reservoirs and rapidly diagnosing cases of henipavirus infection are critical to limiting the spread of these viruses. Current laboratory methods for detecting NiV and HeV include virus isolation, reverse transcription quantitative real-time PCR (RT-qPCR), and antigen detection via an enzyme-linked immunosorbent assay (ELISA), all of which require highly trained personnel and specialized equipment. Here, we describe the development of a point-of-care customized immunochromatographic lateral flow (ILF) assay that uses recombinant human ephrin B2 as a capture ligand on the test line and a NiV-specific monoclonal antibody (mAb) on the conjugate pad to detect NiV and HeV. The ILF assay detects NiV and HeV with a diagnostic specificity of 94.4% and has no cross-reactivity with other viruses. This rapid test may be suitable for field testing and in countries with limited laboratory resources. Full article

This study contributes to the broader sustainability discourse by evaluating public knowledge, awareness, and practices regarding air pollution among residents of Hanoi, Vietnam, focusing on its causes, health impacts, and mitigation strategies. A cross-sectional survey was conducted with 521 individuals in suburbs around Hanoi. A multistage sampling technique, combining cluster and simple random sampling, was used for participant recruitment. Three central and three suburban districts of Hanoi were randomly selected as clusters. One individual from each household was invited to participate and answer a structured survey, which assessed perceptions of air pollution, its human-induced causes, recognised health impacts, and individual and community-level mitigation behaviours. Nearly all participants (98.3%) were aware of air pollution, with 65.3% attributing it to human activities and 61.2% recognising specific air pollutants as primary contributors. The majority (93.9%) acknowledged health impacts, citing respiratory infections (55.1%) and sinus issues (51.2%) as prevalent concerns. Vulnerable groups, such as children under 5 (82.3%) and adults over 65 years old (77.4%), were identified as disproportionately affected. Social media (68.9%) and television (58.3%) were the dominant sources of information. Despite a recognition of air pollution’s importance (98.5%), there was limited engagement in systemic sustainability actions, such as supporting renewable energy initiatives. Most participants (84.3%) reported personal mitigation efforts, including energy-saving practices (35.5%) and walking instead of driving a car or bike (35.3%). While awareness of air pollution and its health impacts is high among Hanoi residents, proactive engagement in systemic solutions remains limited. Policymakers should prioritise community-based programs, public–private partnerships, sustainability education, and culturally tailored policy interventions to bridge gaps between awareness and action. Tailored interventions addressing demographic and cultural factors are essential to fostering socio-environmental sustainability in rapidly urbanising contexts. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) supports critically ill patients with respiratory failure. However, ECMO may induce systemic inflammation, hemolysis, and hemodilution, potentially resulting in endothelial activation and damage. Therefore, this study explored the longitudinal changes in circulating markers of inflammation, hemolysis, and endothelial activation and damage in patients with COVID-19 on VV-ECMO. Methods Plasma was obtained before, within 48 h as well as on day 4, week 1, and week 2 of ECMO support and after decannulation. Circulating markers were measured using Luminex, ELISA, and spectrophotometry. Human pulmonary endothelial cells were exposed to patient plasma, and in vitro endothelial permeability was assessed using electric cell-substrate impedance sensing. Results From April 2020 to January 2022, plasma was collected from 14 patients (71.4% male; age 54 (45–61) years). IL-6 levels decreased (1.238 vs. 0.614 ng/mL, p = 0.039) while ICAM-1 increased (667 vs. 884 ng/mL, p = 0.003) over time when compared to pre-ECMO. Angiopoietin-1 decreased after ECMO initiation (7.57 vs. 3.58 ng/mL, p = 0.030), whereas angiopoietin-2 increased (5.20 vs. 10.19 ng/mL, p = 0.017), particularly in non-survivors of ECMO. Cell-free hemoglobin decreased directly after VV-ECMO initiation but remained stable thereafter (55.29 vs. 9.19 mg/dL, p = 0.017). Moreover, the plasma obtained at several time points during the ECMO run induced in vitro pulmonary endothelial hyperpermeability. Conclusions This exploratory study shows that patients on VV-ECMO support due to COVID-ARDS exhibit progressive endothelial activation and damage but not inflammation and hemolysis. Larger prospective studies are necessary to elucidate pathophysiological pathways leading to endothelial activation and damage, thereby reducing organ failure in these critically ill patients. Full article

Marathon running exerts physical stress and may lead to transient immune dysregulation, increasing susceptibility to airway inflammation and exercise-induced bronchoconstriction (EIB). This study investigated systemic levels of antimicrobial peptides in athletes and their association with EIB. Serum concentrations of angiogenin, human beta-defensin 2 (hBD-2), major basic protein (MBP), S100A8, and S100A8/A9 were measured in 34 marathoners and 36 half-marathoners at baseline, immediately after a race, and seven days postrace using enzyme-linked immunosorbent assays and compared with 30 sedentary controls. Lung function was assessed by spirometry to identify bronchoconstriction. Levels of hBD-2 and S100A8/A9 were significantly elevated postrace in runners compared to baseline and controls, returning to baseline during recovery. During recovery, S100A8 levels remained slightly elevated in marathoners with EIB. Similarly, human beta-defensin 2 was modestly increased in runners who developed bronchoconstriction. Notably, S100A8 levels correlated negatively with lung function parameters, including forced expiratory volume and mid-expiratory flows. These findings suggest that endurance running induces systemic inflammatory responses and modulates innate immune peptides, particularly in individuals prone to bronchoconstriction. These peptides may serve as biomarkers of respiratory stress and help guide personalized strategies in endurance sports. Full article

Calreticulin is a highly conserved and multifunctional molecular chaperone ubiquitously expressed in humans and animals. Beyond its well-established roles in calcium homeostasis, protein folding, and immune regulation, recent studies in aquatic species have suggested a previously unrecognized antimicrobial function of calreticulin. These findings raise the question of whether calreticulin also exerts antibacterial activity in terrestrial mammals, which has not been systematically investigated to date. To address this knowledge gap, we successfully constructed and expressed recombinant goat calreticulin using the Pichia pastoris expression system, yielding a protein of over 99% purity that predominantly exists in dimeric form. Functional assays demonstrated that both recombinant goat and human calreticulin exhibited preliminary inhibitory activity against Escherichia coli, Salmonella typhimurium, and Pasteurella multocida. Calreticulin was capable of binding to these three bacterial species as well as bacterial lipopolysaccharides (LPS). Notably, in the presence of Ca²⁺, calreticulin induced bacterial aggregation, indicating a potential mechanism for limiting bacterial dissemination and proliferation. Given the high anatomical, genetic, and physiological similarity between goats and humans—particularly in respiratory tract structure and mucosal immune function—neonatal goats were selected as a relevant model for evaluating the in vivo antimicrobial efficacy of calreticulin. Accordingly, we established an intranasal infection model using Pasteurella multocida to assess the protective role of calreticulin against respiratory bacterial challenge. Following infection, calreticulin expression was markedly upregulated in the nasal mucosa, trachea, and lung tissues. Moreover, intranasal administration of exogenous calreticulin significantly alleviated infection-induced pathological injury to the respiratory system and effectively decreased bacterial loads in infected tissues. Collectively, this study systematically elucidates the antimicrobial activity of calreticulin in a mammalian model and highlights its potential as a natural immune effector, providing novel insights for the development of host-targeted antimicrobial strategies. Full article

Streptococcus pyogenes is a bacterial pathogen known to be the causative agent in many different illnesses, with Group A Streptococcus (GAS) pharyngitis (strep throat), being one of the more prevalent. The spread and severity of GAS pharyngitis can grow exponentially if individuals are not taking the proper precautions. Wastewater surveillance has been used to test for numerous different pathogens that humans spread throughout a community and in this study, we utilized wastewater surveillance to monitor GAS pharyngitis in a small city. Over a year, 57 wastewater influent samples were tested for S. pyogenes and three commonly tested respiratory viruses (Respiratory Syncytial Virus (RSV), SARS-CoV-2, Influenza A). Three microbial indicators and population normalizers (CrAssphage, Pepper mild mottle virus (PMMoV), and Mycobacterium) were tested as well to compare and contrast each indicator’s value and range over time. Wastewater data was then compared to publicly available search term data as clinical data was not readily available. There was a high correlation between the collected molecular data and the publicly available search term data for Streptococcus pyogenes. Additionally, this study provided more information about the seasonal trend of S. pyogenes throughout the year through molecular data and allowed for the ability to track peak infection months in this small city. Overall, these results highlight the substantial benefits of using wastewater surveillance for the monitoring of GAS pharyngitis. This study also provides helpful insights into future studies about the prevalence of respiratory bacteria and their seasonal trends in wastewater, allowing for public health systems to provide mitigation strategies. Full article

For centuries, traditional medical systems have utilized Cistus leaf infusions, extracts, and essential oils in the treatment of inflammatory conditions, respiratory infections, febrile illnesses, and gastrointestinal disorders. Contemporary research has increasingly focused on the identification and characterization of biologically active constituents—particularly polyphenols and other antioxidants—that may modulate key physiological and cellular processes in the human body. These include mechanisms related to oxidative stress, inflammation, aging, and carcinogenesis. The therapeutic relevance of Cistus-derived compounds is further supported by their generally favorable safety profile and high tolerability, which distinguishes them from many synthetic pharmaceuticals. Moreover, the accessibility of Cistus preparations as dietary supplements or herbal infusions allows for their regular consumption without the need for complex therapeutic regimens. This positions Cistus as a promising candidate for integrative health strategies aimed at disease prevention and health maintenance. This review provides a comprehensive overview of the pharmacological potential and therapeutic applications of Cistus extracts, with particular emphasis on their antioxidant and bioactive properties. Full article

The One Health approach is rapidly gaining the attention of the scientific community worldwide and is expected to be a major model of scientific reasoning in the 21st century, concerning medical, veterinary and environmental issues. The basic concept of One Health, that humans, animals and their environments are parts of the same natural world affecting each other, is rooted in most ethnic as well as in many religious traditions. Despite this unity and for historical reasons, medical, veterinary and environmental sciences developed independently. The One Health concept tries to reunite these and many other relevant sciences, aiming at a deeper understanding of the interconnection between the natural world, humans and animal health. The dynamic interplay between a host’s microbiome, the microbiomes of other hosts, and environmental microbial communities profoundly influences the host health, given the essential physiological functions the microbiome performs within the organism. The biodiversity of microbiomes is broad and complex. The different areas of the skin, the upper and lower respiratory systems, the ocular cavity, the oral cavity, the gastrointestinal tract and finally the urogenital system of pets and humans alike are niches where a multitude of microorganisms indigenous and transient—commensals and pathogens, thrive in a dynamic antagonistic balance of populations of different phyla, orders, genera and species. The description of these microbiomes attempted in this article is not meant to be exhaustive but rather demonstrative of their complexity. The study of microbiomes is a necessary step towards the One Health approach to pets and humans. Yet, despite the progress made on that subject, the scientific community faces challenges, such as the limitations of studies performed, the scarcity of studies concerning the microbiomes of cats, the multitude of environmental factors affecting the results and others. The two new terms proposed in this article, the “familiome” and the “oikiome”, will aid in the One Health theoretical analysis as well as in its practical approach. The authors strongly believe that new technological breakthroughs, like Big Data Analytics and Artificial Intelligence (AI), will significantly help to overcome these hazards. Full article

Saxitoxin (STX) is a potent toxin produced by marine dinoflagellates and freshwater or brackish water cyanobacteria, and is a member of the paralytic shellfish toxins (PSTs). As a highly specific blocker of voltage-gated sodium channels (NaVs), STX blocks sodium ion influx, thereby inhibiting nerve impulse transmission and leading to systemic physiological dysfunctions in the nervous, respiratory, cardiovascular, and digestive systems. Severe exposure can lead to paralysis, respiratory failure, and mortality. STX primarily enters the human body through the consumption of contaminated shellfish, posing a significant public health risk as the causative agent of paralytic shellfish poisoning (PSP). Beyond its acute toxicity, STX exerts cascading impacts on food safety, marine ecosystem integrity, and economic stability, particularly in regions affected by harmful algal blooms (HABs). Moreover, the complex molecular structure of STX—tricyclic skeleton and biguanide group—and its diverse analogs (more than 50 derivatives) have made it the focus of research on natural toxins. In this review, we traced the discovery history, chemical structure, molecular biosynthesis, biological enrichment mechanisms, and toxicological actions of STX. Moreover, we highlighted recent advancements in the potential for detection and treatment strategies of STX. By integrating multidisciplinary insights, this review aims to provide a holistic understanding of STX and to guide future research directions for its prevention, management, and potential applications. Full article

Context: Respiratory morbidity is a leading cause of children’s consultations with general practitioners. Auscultation, the act of listening to breath sounds, is a crucial diagnostic method for respiratory system diseases. Problem: Parents and caregivers often lack the necessary knowledge and experience to identify subtle differences in children’s breath sounds. Furthermore, obtaining reliable feedback from young children about their physical condition is challenging. Methods: The use of a human–artificial intelligence (AI) tool is an essential component for screening and monitoring young children’s respiratory diseases. Using clinical data to design and validate the proposed approaches, we propose novel methods for recognizing and classifying children’s breath sounds. Different breath sound signals were analyzed in the time domain, frequency domain, and using spectrogram representations. Breath sound detection and segmentation were performed using digital signal processing techniques. Multiple features—including Mel–Frequency Cepstral Coefficients (MFCCs), Linear Prediction Coefficients (LPCs), Linear Prediction Cepstral Coefficients (LPCCs), spectral entropy, and Dynamic Linear Prediction Coefficients (DLPCs)—were extracted to capture both time and frequency characteristics. These features were then fed into various classifiers, including K-Nearest Neighbor (KNN), artificial neural networks (ANNs), hidden Markov models (HMMs), logistic regression, and decision trees, for recognition and classification. Main Findings: Experimental results from across 120 infants and preschoolers (2 months to 6 years) with respiratory disease (30 asthma, 30 croup, 30 pneumonia, and 30 normal) verified the performance of the proposed approaches. Conclusions: The proposed AI system provides a real-time diagnostic platform to improve clinical respiratory management and outcomes in young children, thereby reducing healthcare costs. Future work exploring additional respiratory diseases is warranted. Full article