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The purpose of this work is to estimate the aerodynamic characteristics of the stepped nacelle of a gas turbine engine with a turbofan unit. The research was based on the method of model physical experiment. The wind tunnel applied for the study was provided with the necessary equipment, which includes various nozzles of static and dynamic pressure with coordinate devices, etc. For the experimental study, we built the models of nacelles for an aviation power plant with front location of the fan module and with the rear arrangement of a turbofan unit. We have experimentally investigated the aerodynamic characteristics of the stepped nacelle for a gas turbine engine with a turbofan unit. The results of this study demonstrated a possibility to decrease the aerodynamic drag of the stepped nacelle for an engine with a turbofan unit compared to the nacelle of a turbojet double-pass engine with the front arrangement of the fan. In the range of angles of attack α = 0...20° the value of aerodynamic drag of the stepped nacelle for a gas turbine engine with a turbofan unit decreases by 49...55 %. The obtained results showed that the coefficient of lifting power of the stepped nacelle for a gas turbine engine with a turbofan unit increases by 24...64 %. The coefficient of aerodynamic drag is lower by 18...28 % compared with the aerodynamic drag coefficient of a cylindrical nacelle for a double-pass turbojet engine in the range of angles of attack α = 2...20°. Our findings indicate the prospects of using engines with a turbofan unit. The structural feature of the stepped nacelle would reduce the loss of efficient engine thrust by decreasing aerodynamic drag almost by two times and could increase fuel efficiency of the engine. [ABSTRACT FROM AUTHOR]

Collagen is a popular nutricosmetic ingredient in food supplements due to its anti-aging and other positive effects on the skin. Due to its widespread use and the lack of regulation in this area, appropriate quality control is required to ensure efficacy and safety, with the development of analytical methods playing an important role. Currently, the quantitative determination of collagen is mainly based on time-consuming derivatization-based spectroscopic methods or on complex chromatographic methods with mass spectrometric detection. Therefore, in this study, two new, simple chromatographic methods have been developed. One is intended for the analysis of untreated samples and is characterized by the speed and simplicity of sample preparation. The other method quantifies collagen via the underivatized tripeptide Gly-Pro-Hyp formed by bacterial collagenase hydrolysis and is characterized by its specificity and ability to distinguish between marine and terrestrial collagen. The latter is a novelty in the field of simple methods for collagen analysis and is particularly important in terms of safety. Our comparison with established analytical methods (e.g., via hydroxyproline after complete hydrolysis) for collagen analysis undoubtedly showed the superiority of these new methods for the routine quality control of collagen supplements in terms of specificity, repeatability, sample stability, and simplification in sample preparation. The collagen content in the supplements tested was found to be adequate; however, some discrepancies were found regarding the labeling and origin of the collagen, with possible safety implications. [ABSTRACT FROM AUTHOR]

Increased circulating tissue inhibitor of metalloproteinases‐1 (TIMP‐1) levels have been observed in patients with acute lung injury (ALI). However, the sex‐specific regulation of TIMP‐1 and the underlying molecular mechanisms have not been well elucidated. In this study, we found that plasma TIMP‐1 levels were significantly higher in COVID‐19 and H1N1 patients compared with those in healthy subjects (n = 25). TIMP‐1 concentrations were significantly different between males and females in each disease group. Among female but not male patients, TIMP‐1 levels significantly correlated with the PaO2/FiO2 ratio and hospital length of stay. Using the mouse model of ALI induced by the H1N1 virus, we found that TIMP‐1 is strikingly induced in PDGFRα‐positive cells in the murine lungs. Moreover, female mice showed a higher Timp‐1 expression in the lungs on day 3 postinfection. Mechanistically, we observed that estrogen can upregulate TIMP‐1 expression in lung fibroblasts, not epithelial cells. In addition, overexpression of estrogen receptor α (ERα) increased the TIMP‐1 promoter activity. In summary, TIMP‐1 is an estrogen‐responsive gene, and its promoter activity is regulated by ERα. Circulating TIMP‐1 may serve as a sex‐specific marker, reflecting the severity and worst outcomes in female patients with SARS‐CoV2‐ and IAV‐related ALI. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) infection can increase the risk of neuroinflammation, and subsequent neurodegenerative diseases. Certain IAV strains, such as avian H7N7 subtype, possess neurotropic properties, enabling them to directly invade the brain parenchyma and infect neurons and glia cells. Host sex significantly influences the severity of IAV infections. Studies indicate that females of the reproductive age exhibit stronger innate and adaptive immune responses to IAVs compared to males. This heightened immune response correlates with increased morbidity and mortality, and potential neuronal damage in females. Understanding the sex-specific neurotropism of IAV and associated mechanisms leading to adverse neurological outcomes is essential. Our study reveals that primary hippocampal cultures from female mice show heightened interferon-β and pro-inflammatory chemokine secretion following neurotropic IAV infection. We observed sex-specific differences in microglia activation: both sexes showed a transition into a hyper-ramified state, but only male-derived microglia exhibited an increase in amoeboid-shaped cells. These disparities extended to alterations in neuronal morphology. Neurons derived from female mice displayed increased spine density within 24 h post-infection, while no significant change was observed in male cultures. This aligns with sex-specific differences in microglial synaptic pruning. Data suggest that amoeboid-shaped microglia preferentially target postsynaptic terminals, potentially reducing neuronal hyperexcitability. Conversely, hyper-ramified microglia may focus on presynaptic terminals, potentially limiting viral spread. In conclusion, our findings underscore the utility of primary hippocampal cultures, incorporating microglia, as an effective model to study sex-specific, virus-induced effects on brain-resident cells. [ABSTRACT FROM AUTHOR]

Integrated bioinformatics tools have created more efficient and robust methods to overcome in vitro challenges and have been widely utilized for the investigation of food proteins and the generation of peptide sequences. This study aimed to analyze the physicochemical properties and bioactivities of novel peptides derived from hydrolyzed milkfish (Chanos chanos) protein sequences and to discover their potential angiotensin-converting enzyme (ACE)- and dipeptidyl peptidase-4 (DPPIV)-inhibitory activities using machine learning-based tools, including BIOPEP-UWM, PeptideRanker, and the molecular docking software HADDOCK 2.4. Nine and three peptides were predicted to have ACE- and DPPIV-inhibitory activities, respectively. The DPPIV-inhibitory peptides were predicted to inhibit the compound with no known specific mode. Meanwhile, two tetrapeptides (MVWH and PPPS) were predicted to possess a competitive mode of ACE inhibition by directly binding to the tetra-coordinated Zn ion. Among all nine discovered ACE-inhibitory peptides, only the PPPS peptide satisfied the drug-likeness analysis requirements with no violations of the Lipinski rule of five and should be further investigated in vitro. [ABSTRACT FROM AUTHOR]

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Given the ongoing rise in the occurrence of allergic disorders, alterations in dietary patterns have been proposed as a possible factor contributing to the emergence and progression of these conditions. Currently, there is a significant focus on the development of dietary therapies that utilize natural compounds possessing anti-allergy properties. Dietary polyphenols and plant metabolites have been intensively researched due to their well-documented anti-inflammatory, antioxidant, and immunomodulatory characteristics, making them one of the most prominent natural bioactive chemicals. This study seeks to discuss the in-depth mechanisms by which these molecules may exert anti-allergic effects, namely through their capacity to diminish the allergenicity of proteins, modulate immune responses, and modify the composition of the gut microbiota. However, further investigation is required to fully understand these effects. This paper examines the existing evidence from experimental and clinical studies that supports the idea that different polyphenols, such as catechins, resveratrol, curcumin, quercetin, and others, can reduce allergic inflammation, relieve symptoms of food allergy, asthma, atopic dermatitis, and allergic rhinitis, and prevent the progression of the allergic immune response. In summary, dietary polyphenols and plant metabolites possess significant anti-allergic properties and can be utilized for developing both preventative and therapeutic strategies for targeting allergic conditions. The paper also discusses the constraints in investigating and broad usage of polyphenols, as well as potential avenues for future research. [ABSTRACT FROM AUTHOR]

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders. [ABSTRACT FROM AUTHOR]

The increased incidence of osteoarthritis (OA), particularly knee and hip OA, and osteoporosis (OP), owing to population aging, have escalated the medical expense burden. Osteoarthritis is more prevalent in older women, and the involvement of subchondral bone fragility spotlights its association with OP. Notably, subchondral insufficiency fracture (SIF) may represent a more pronounced condition of OA pathophysiology. This review summarizes the relationship between OA and OP, incorporating recent insights into SIF. Progressive SIF leads to joint collapse and secondary OA and is associated with OP. Furthermore, the thinning and fragility of subchondral bone in early-stage OA suggest that SIF may be a subtype of OA (osteoporosis-related OA, OPOA) characterized by significant subchondral bone damage. The high bone mineral density observed in OA may be overestimated due to osteophytes and sclerosis and can potentially contribute to OPOA. The incidence of OPOA is expected to increase along with population aging. Therefore, prioritizing OP screening, early interventions for patients with early-stage OA, and fracture prevention measures such as rehabilitation, fracture liaison services, nutritional management, and medication guidance are essential. [ABSTRACT FROM AUTHOR]

Epigenetic alterations such as dysregulation of miRNAs have been reported to play important roles in interactions between genetic and environmental factors. In this study, we tested the hypothesis that induction of lung inflammation by inhaled allergens triggers a sex-specific miRNA regulation that is dependent on chromosome complement and hormonal milieu. We challenged the four core genotypes (FCGs) model through intranasal sensitization with a house dust mite (HDM) solution (or PBS as a control) for 5 wk. The FCG model allows four combinations of gonads and sex chromosomes: 1) XX mice with ovaries (XXF), 2) XY mice with testes (XYM), 3) XX mice with testes (XXM), and 4) XY mice with ovaries (XYF). Following the challenge (n ¼ 5–7/ group), we assessed the expression of 84 inflammatory miRNAs in lung tissue using a PCR array and cytokine levels in bronchoalveolar lavage fluid (BAL) by a multiplex protein assay (n ¼ 4–7 animals/group). Our results showed higher levels of the chemokine KC (an Il-8 homolog) and IL-7 in BAL from XYF mice challenged with HDM. In addition, IL-17A was significantly higher in BAL from both XXF and XYF mice. A three-way interaction among treatment, gonads, and sex chromosome revealed 60 of 64 miRNAs that differed in expression depending on genotype; XXF, XXM, XYF, and XYM mice had 45, 32, 4, and 52 differentially expressed miRNAs, respectively. Regulatory networks of miRNAs identified in this study were implicated in pathways associated with asthma. Female gonadal hormonal effects may alter miRNA expression and contribute to the higher susceptibility of females to asthma. NEW & NOTEWORTHY miRNAs play important roles in regulating gene and environmental interactions. However, their role in mediating sex differences in allergic responses and lung diseases has not been elucidated. Our study used a targeted omics approach to characterize the contributions of gonadal hormones and chromosomal components to lung responses to an allergen challenge. Our results point to the influence of sex hormones in miRNA expression and proinflammatory markers in allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Bronchial asthma is an extremely heterogenous chronic respiratory disorder with several distinct endotypes and phenotypes. These subtypes differ not only in the pathophysiological changes and/or clinical features but also in their response to the treatment. Therefore, precise diagnostics represent a fundamental condition for effective therapy. In the diagnostic process, metabolomic approaches have been increasingly used, providing detailed information on the metabolic alterations associated with human asthma. Further information is brought by metabolomic analysis of samples obtained from animal models. This article summarizes the current knowledge on metabolomic changes in human and animal studies of asthma and reveals that alterations in lipid metabolism, amino acid metabolism, purine metabolism, glycolysis and the tricarboxylic acid cycle found in the animal studies resemble, to a large extent, the changes found in human patients with asthma. The findings indicate that, despite the limitations of animal modeling in asthma, pre-clinical testing and metabolomic analysis of animal samples may, together with metabolomic analysis of human samples, contribute to a novel way of personalized treatment of asthma patients. [ABSTRACT FROM AUTHOR]

At present, medications containing inhaled corticosteroids (ICS-containing) are the keystones of asthma treatment. The majority of asthmatic children can significantly improve clinical outcomes with little worsening by standardized inhaled glucocorticoid treatment, but there is still a small proportion of children who are unable to achieve good symptom control even after the maximum standardized treatment, known as 'children with difficult-to-treat asthma (DA)'. The high heterogeneity of DA makes therapy challenging and expensive, which poses a serious risk to children's health and makes it extremely difficult for clinical physicians to accurately identify and treat children with DA. This article reviews the definition, evaluation, and treatment of this asthma in order to provide a reference for optimal clinical decision-making. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice. [ABSTRACT FROM AUTHOR]

In light of the constantly increasing prevalence of allergic diseases, changes in dietary patterns have been suggested as a plausible environmental explanation for the development and progression of these diseases. Nowadays, much attention has been paid to the development of dietary interventions using natural substances with anti-allergy activities. In this respect, dietary polyphenols have been studied extensively as one of the most prominent natural bioactive compounds with well-documented anti-inflammatory, antioxidant, and immunomodulatory properties. This review aims to discuss the mechanisms underlying the potential anti-allergic actions of polyphenols related to their ability to reduce protein allergenicity, regulate immune response, and gut microbiome modification; however, these issues need to be elucidated in detail. This paper reviews the current evidence from experimental and clinical studies confirming that various polyphenols such as quercetin, curcumin, resveratrol, catechins, and many others could attenuate allergic inflammation, alleviate the symptoms of food allergy, asthma, and allergic rhinitis, and prevent the development of allergic immune response. Conclusively, dietary polyphenols are endowed with great anti-allergic potential and therefore could be used either for preventive approaches or therapeutic interventions in relation to allergic diseases. Limitations in studying and widespread use of polyphenols as well as future research directions are also discussed. [ABSTRACT FROM AUTHOR]

Since the outbreak of COVID‐19, many antiviral drugs have been used to treat infected patients. Excessive drug concentrations may not only damage patients' organs, but also lead to increased mortality. The lack of data makes it difficult for them to be treated with these drugs under proper and safe dosage. However, due to the complexity of fluid matrixand structures of the antiviral drugs, it is still difficult to detect the drugs in biofluids. Herein, solid‐phase microextraction (SPME) is applied for the detection of biological matrix, which has the advantages of simplicity, efficiency and environmental protection. With abundant hydrogen bond sites and appropriate molecular volume, biocompatible graded‐pore HOF10x series materials are selected as the fiber coating for exploration. Consequently, HOF101 could achieve high enrichment effect of drugs due to the commensurate mesopores and hydrogen bond non‐covalent interaction. Moreover, the excellent extraction capacity of the HOF101 fiber is verified to be consistent in various interfering conditions. The obtained limits of detections (LODs) are 0.24–0.66 ng L−1, and the recoveries of the biofluids in three concentration levels ranged from 80.30% to 120.1%. It shows the low LODs and satisfactory recoveries of this analytical method, which is expected to be applied in medical systems for drug monitoring. [ABSTRACT FROM AUTHOR]

Fish is one of the "big nine" foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies. [ABSTRACT FROM AUTHOR]

Purpose of Review: A significant fraction of allergens bind small molecular ligands, and many of these compounds are classified as lipids. However, in most cases, we do not know the role that is played by the ligands in the allergic sensitization or allergic effector phases. Recent Findings: More effort is dedicated toward identification of allergens' ligands. This resulted in identification of some lipidic compounds that can play active immunomodulatory roles or impact allergens' molecular and allergic properties. Summary: Four allergen families (lipocalins, NPC2, nsLTP, and PR-10) are among the best characterized in terms of their ligand-binding properties. Allergens from these four families are able to bind many chemically diverse molecules. These molecules can directly interact with human immune system and/or affect conformation and stability of allergens. While there is more data on the allergens and their small molecular ligands, we are just starting to understand their role in allergy. [ABSTRACT FROM AUTHOR]

Avian influenza viruses (AIV) are a continuous cause of concern due to their pandemic potential and devasting effects on poultry, birds, and human health. The low pathogenic avian influenza virus has the potential to evolve into a highly pathogenic avian influenza virus, resulting in its rapid spread and significant outbreaks in poultry. Over the years, a wide array of traditional and novel strategies has been implemented to prevent the transmission of AIV in poultry. Mass vaccination is still an economical and effective approach to establish immune protection against clinical virus infection. At present, some AIV vaccines have been licensed for large-scale production and use in the poultry industry; however, other new types of AIV vaccines are currently under research and development. In this review, we assess the recent progress surrounding the various types of AIV vaccines, which are based on the classical and next-generation platforms. Additionally, the delivery systems for nucleic acid vaccines are discussed, since these vaccines have attracted significant attention following their significant role in the fight against COVID-19. We also provide a general introduction to the dendritic targeting strategy, which can be used to enhance the immune efficiency of AIV vaccines. This review may be beneficial for the avian influenza research community, providing ideas for the design and development of new AIV vaccines. [ABSTRACT FROM AUTHOR]

The major cat allergen Fel d 1 is a tetrameric glycoprotein from the secretoglobin superfamily. Fel d 1's biological role is unknown, but it has been previously shown that it participates in semiochemical binding/transportation. Fel d 1 has linear epitopes, but its conformational epitope sites remain unclear. In this study, we predicted the B-cell epitopes of Fel d 1 and explored semiochemical dynamics with epitopes using bioinformatics tools. The epitope residues were tabulated for chains 1 and 2 and the heterodimers of Fel d 1. The residual interactions of Fel d 1 with IgE were evaluated, and the prominent epitope sites were predicted. The molecular dynamics simulation (MDS) of Fel d 1 was performed with seven reported semiochemicals to evaluate the Fel d 1–ligand complex stability and decipher the semiochemical effect on Fel d 1 conformational epitopes. Fel d 1–lauric acid, Fel d 1–oleic acid, and Fel d 1–progesterone showed more stability and less fluctuation than other compounds. Fel d 1–linoleic acid and Fel d 1–pregnenolone displayed the most unstable complex with fluctuations. The effects of conformational changes on epitopes are discussed. All the ligand complexes drive substantial fluctuation towards the functionally exposed IgE-binding epitopes. Fel d 1 could be examined for its ligand-binding and conformational changes caused by mutations of B-cell epitopes. [ABSTRACT FROM AUTHOR]

Biomaterial-based therapies have been receiving attention for treating microbial infections mainly to overcome the increasing number of drug-resistant bacterial strains and off-target impacts of therapeutic agents by conventional strategies. A fibrous, non-soluble protein, collagen, is one of the most studied biopolymers for the development of antimicrobial biomaterials owing to its superior physicochemical, biomechanical, and biological properties. In this study, we reviewed the different approaches used to develop collagen-based antimicrobial devices, such as non-pharmacological, antibiotic, metal oxide, antimicrobial peptide, herbal extract-based, and combination approaches, with a particular focus on preclinical studies that have been published in the last decade. [ABSTRACT FROM AUTHOR]

Eosinophils play a key role in airway inflammation in many diseases, such as allergic and non-allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic obstructive pulmonary disease. In these chronic disabling conditions, eosinophils contribute to tissue damage, repair, remodeling, and disease persistence through the production a variety of mediators. With the introduction of biological drugs for the treatment of these respiratory diseases, the classification of patients based on clinical characteristics (phenotype) and pathobiological mechanisms (endotype) has become mandatory. This need is particularly evident in severe asthma, where, despite the great scientific efforts to understand the immunological pathways underlying clinical phenotypes, the identification of specific biomarkers defining endotypes or predicting pharmacological response remains unsatisfied. In addition, a significant heterogeneity also exists among patients with other airway diseases. In this review, we describe some of the immunological differences in eosinophilic airway inflammation associated with severe asthma and other airway diseases and how these factors might influence the clinical presentation, with the aim of clarifying when eosinophils play a key pathogenic role and, therefore, represent the preferred therapeutic target. [ABSTRACT FROM AUTHOR]

The discourse of the Anthropocene expresses an interesting tension in the way human causation and guilt are framed. On the one hand, the Anthropos is a unique species, making historical, geographical and geological conquest single-handedly (to the exclusion of non-human subjects). A triumphant and increasingly dominant coloniser of a planet that ultimately falls very low, indeed. In the light of the impending climate catastrophe, the "age of man" no longer sounds so noble today. On the contrary, it becomes a testimony of discredit and decline, a sign of egoism and planetary destruction by one species. Among the many approaches and attempts to address and nuance the discourse and amidst the search for the most appropriate labels (e.g. Capitalocene, chtchulucene, ecozoic, etc.), it is the Anthropocene or post-Anthropocene that seem to remain the ones most frequently referred to in colloquial or journalistic discourse. A need arises to clearly identify the one to blame for the impending climatic apocalypse. Under conditions of crisis, during what Girard call undifferentiation, the Anthropos selects itself as the scapegoat, becoming both the unfortunate, guilt-ridden OTHER and the ruthless, violence-hungry MOB. Could René Girard's concept of mimesis and scapegoating help to understand the pattern of this dialectical, subversive strategy? If so, then perhaps it is to be expected that the stage of sacralisation of the victim, which crowns the logic of scapegoating, instead of overcoming it, will only perpetuate the apotheosis of human agency, dangerous from the point of view of the actual state of the planet. This time, these will be essentially anthropocentric and technologically advanced "escapes forward", such as exploitation of the moon or other planets, invasive prevention of further ice and greenhouse ages, deflecting asteroids so that they do not collide with Earth, and other, hardly predictable spectacular gestures of the triumphant Anthropos. The above questions are the subject matter of this article and a pretext for pedagogical reflection. [ABSTRACT FROM AUTHOR]

Purpose of Review: Allergic diseases represent a major health problem of increasing prevalence worldwide. In allergy, dendritic cells (DCs) contribute to both the pathophysiology and the induction of healthy immune responses to the allergens. Different studies have reported that some common allergens contain glycans in their structure. C-type lectin receptors (CLRs) expressed by DCs recognize carbohydrate structures and are crucial in allergen uptake, presentation, and polarization of T cell responses. This review summarizes the recent literature regarding the role of CLRs in the regulation of type 2 immune responses to allergens. Recent Findings: In this review, we highlight the capacity of CLRs to recognize carbohydrates in common allergens triggering different signaling pathways involved in the polarization of CD4+ T cells towards specific Th2 responses. Under certain conditions, specific CLRs could also promote tolerogenic responses to allergens, which might well be exploited to develop novel therapeutic approaches of allergen-specific immunotherapy (AIT), the single treatment with potential disease-modifying capacity for allergic disease. At this regard, polymerized allergens conjugated to non-oxidized mannan (allergoid-mannan conjugated) are next-generation vaccines targeting DCs via CLRs that promote regulatory T cells, thus favoring allergen tolerance both in preclinical models and clinical trials. Summary: A better understanding of the role of CLRs in the development of allergy and in the induction of allergen tolerance might well pave the way for the design of novel strategies for allergic diseases. [ABSTRACT FROM AUTHOR]

Food allergy represents a growing public health and socio-economic problem with an increasing prevalence over the last two decades. Despite its substantial impact on the quality of life, current treatment options for food allergy are limited to strict allergen avoidance and emergency management, creating an urgent need for effective preventive strategies. Advances in the understanding of the food allergy pathogenesis allow to develop more precise approaches targeting specific pathophysiological pathways. Recently, the skin has become an important target for food allergy prevention strategies, as it has been hypothesized that allergen exposure through the impaired skin barrier might induce an immune response resulting in subsequent development of food allergy. This review aims to discuss current evidence supporting this complex interplay between the skin barrier dysfunction and food allergy by highlighting the crucial role of epicutaneous sensitization in the causality pathway leading to food allergen sensitization and progression to clinical food allergy. We also summarize recently studied prophylactic and therapeutic interventions targeting the skin barrier repair as an emerging food allergy prevention strategy and discuss current evidence controversies and future challenges. Further studies are needed before these promising strategies can be routinely implemented as prevention advice for the general population. [ABSTRACT FROM AUTHOR]

We describe perioperative anaphylaxis following intravenous clindamycin in two healthy adolescent patients with prior transcutaneous clindamycin sensitization. Prior to their third molar extractions, both patients were only previously exposed to clindamycin via topical acne gels, which primed their immune system for the observed response. Cognizance of the classic signs of anaphylaxis is paramount so that any procedure or infusion can be halted immediately, and the condition treated appropriately. We anticipate the frequency of such reactions to increase, particularly among adolescents, given the frequency of clindamycin use in oral and maxillofacial surgical procedures, the prevalence of third molar extractions among the paediatric population, and the widespread topical antibiotic use in acne treatments that can sensitize the immune system for anaphylaxis upon internal antigen reintroduction. [ABSTRACT FROM AUTHOR]

The allergic march is a progression of naturally occurring symptoms whose nature changes with age. The classic allergic march typically begins in infancy and manifests in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3–5 years; however, they may evolve into allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. Recent years saw the emergence of precision allergy molecular diagnosis (PAMD@), which assesses sIgE against allergenic molecules. This new technology helps more accurately evaluate the patient's allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy. This review presents possible predictions regarding the allergic march and the means of controlling it based on PAMD@ results. [ABSTRACT FROM AUTHOR]

Peach allergy is among the most frequent food allergies in the Mediterranean area, often eliciting severe anaphylactic reactions in patients. Due to the risk of severe symptoms, studies in humans are limited, leading to a lack of therapeutic options. This study aimed to develop a peach allergy mouse model as a tool to better understand the pathomechanism and to allow preclinical investigations on the development of optimized strategies for immunotherapy. CBA/J mice were sensitized intraperitoneally with peach extract or PBS, using alum as adjuvant. Afterwards, extract was administered intragastrically to involve the intestinal tract. Allergen provocation was performed via intraperitoneal injection of extract, measuring drop of body temperature as main read out of anaphylaxis. The model induced allergy-related symptoms in mice, including decrease of body temperature. Antibody levels in serum and intestinal homogenates revealed a Th2 response with increased levels of mMCPT-1, peach- and Pru p 3-specific IgE, IgG1 and IgG2a as well as increased levels of IL-4 and IL-13. FACS analysis of small intestine lamina propria revealed increased amounts of T cells, neutrophils and DCs in peach allergic mice. These data suggest the successful establishment of a peach allergy mouse model, inducing systemic as well as local gastrointestinal reactions. [ABSTRACT FROM AUTHOR]

Despite emerging evidence and advances in the management of atopic dermatitis there a lack of consensus regarding the diagnostic criteria, therapeutic approach, method to assess severity, and patient follow-up for this condition. An expert consensus study was conducted to provide recommendations on the management of patients with moderate-to-severe atopic dermatitis. The study used Delphi-like methodology based on a literature review, a summary of the scientific evidence, and a 2-round survey. The agreement of 60 panellists on 21 statements was evaluated. Consensus was predefined as ≥80% agreement of all respondents. In the first round 6 statements reached consensus. Unanimous consensus was achieved regarding therapeutic goals and patient satisfaction (maintained in the long term and periodic goals reassessment recommended every 3–6 months). In the second round, half of the statements reached consensus, all related to patient follow-up, treatment goals, and atopic comorbidities. The statements that did not reach consensus were related to diagnosis (biomarkers, allergy, and food testing) and starting patients on conventional systemic treatment rather than advanced treatment. The study assessed expert opinion regarding a variety of topics related to the clinical approach to patients with moderate-to-severe atopic dermatitis, in order to provide guidance on the diagnosis and management of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

At present, medications containing inhaled corticosteroids (ICS-containing) are the keystones of asthma treatment. The majority of asthmatic children can significantly improve clinical outcomes with little worsening by standardized inhaled glucocorticoid treatment, but there is still a small proportion of children who are unable to achieve good symptom control even after the maximum standardized treatment, known as 'children with difficult-to-treat asthma (DA)'. The high heterogeneity of DA makes therapy challenging and expensive, which poses a serious risk to children's health and makes it extremely difficult for clinical physicians to accurately identify and treat children with DA. This article reviews the definition, evaluation, and treatment of this asthma in order to provide a reference for optimal clinical decision-making. [ABSTRACT FROM AUTHOR]

Menopausal women often face long-term estrogen treatment. G protein-coupled estrogen receptor (GPER) expressed in intestinal crypt was activated by estrogen therapy, but it was unclear whether chronic GPER activation duringmenopause had an effect on intestinal stem cells (ISCs). We tested the effect of chronic GPER activation on ISCs of ovariectomized (OVX) mice by injection of the selective GPER agonist G-1 for 28 days, or G-1 stimulation of organoids derived from crypts of OVX mice. G-1 up-regulated crypt depth, the number of Ki67+, bromodeoxyuridine+ cells and Olfm4+ ISCs, and the expression of ISCs marker genes (Lgr5, Olfm4 and Axin2). G-1 administration promoted organoid growth, increased the number of EdU+ cells per organoid and protein expression of Cyclin D1 and cyclin B1 in organoids. After G-1 treatment in vivo or in vitro, Paneth cell-derived Wnt3, Wnt3 effector ß-catenin and Wnt target genes c-Myc and Cyclin D1 increased in ileum or organoids. Once blocking the secretion of Wnt3 from Paneth cells, the effects of G-1 on organoids growth, ISCs marker genes and Wnt/ß-catenin signaling were abolished. G-1 did not affect the number of Paneth cells in ex vivo organoids, while activated Mmp7/cryptdin program in Paneth cells, promoted their maturation, and increased the expression of lysozyme protein. G-1 pretreatment in OVX mice inhibited radiation-induced ISCs proliferation injury and enhanced the resistance of mice to intestinal injury. In conclusion, chronic GPER activation prompted the Wnt3 synthesis in Paneth cells, thus increased the proliferation of ISCs via activation of Wnt3/ß-catenin signaling in OVX mice. [ABSTRACT FROM AUTHOR]

Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of diseases caused by Coronavirus have inflicted devastating social and economic outcomes. Undoubtedly, vaccination is the most effective method of eradicating infections and infectious diseases that have been eradicated by vaccinations, including Smallpox and Polio. To date, next-generation vaccine candidates with novel platforms are being approved for emergency use, such as the mRNA and viral vectored vaccines against SARS-CoV-2. Nanoparticle based vaccines are the perfect candidates as they demonstrated targeted antigen delivery, improved antigen presentation, and sustained antigen release while providing self-adjuvanting functions to stimulate potent immune responses. In this review, we discussed most of the recent nanovaccines that have found success in immunization and challenge studies in animal models in comparison with their naked vaccine counterparts. Nanovaccines that are currently in clinical trials are also reviewed. [ABSTRACT FROM AUTHOR]

Artificial antigen-presenting cells (aAPCs) that stably express particular HLA and co-stimulatory molecules by gene transfer have been developed to effectively stimulate T cells. To investigate whether cytochalsin-B-induced membrane vesicles derived from aAPCs (AP-CIMVs) have similar antigen-presenting functions as a cell-free system, T cell responses to different types of antigen presentation were measured using Jurkat reporter cells. First, the aggregation of AP-CIMV, which affects the measurement of function, was inhibited by nuclease treatment to produce uniform AP-CIMVs. The Green fluorescent protein (GFP) expression in Jurkat reporter cells was induced in a dose-dependent manner in groups stimulated with anti-CD3 antibody-coated AP-CIMVs and aAPCs, and anti-CD3/CD28 Dynabead. When Jurkat reporter cells expressing specific T cell receptors were stimulated by AP-CIMVs and aAPCs loaded with CMV pp65 peptide, AP-CIMVs showed similar stimulatory effects to that by aAPC. However, when these Jurkat reporter cells were stimulated by aAPCs endogenously expressing CMV pp65 antigen and their AP-CIMVs, the GFP expression rate by AP-CIMVs was 8.4%, which was significantly lower than 53.2% by aAPCs. Although this study showed a limited T-cell-stimulating effect of AP-CIMVs on endogenously processed antigen presentation, these results provide useful information for the development of improved cell-free systems for T cell stimulation in the future. [ABSTRACT FROM AUTHOR]

The incidence of allergic diseases and their complications are increasing worldwide. Today, people increasingly use natural products, which has been termed a "return to nature". Natural products with healing properties, especially those obtained from plants and bees, have been used in the prevention and treatment of numerous chronic diseases, including allergy and/or inflammation. Propolis is a multi-component resin rich in flavonoids, collected and transformed by honeybees from buds and plant wounds for the construction and adaptation of their nests. This article describes the current views regarding the possible mechanisms and multiple benefits of flavonoids in combating allergy and allergy-related complications. These benefits arise from flavonoid anti-allergic, anti-inflammatory, antioxidative, and wound healing activities and their effects on microbe-immune system interactions in developing host responses to different allergens. Finally, this article presents various aspects of allergy pathobiology and possible molecular approaches in their treatment. Possible mechanisms regarding the antiallergic action of propolis on the microbiota of the digestive and respiratory tracts and skin diseases as a method to selectively remove allergenic molecules by the process of bacterial biotransformation are also reported. [ABSTRACT FROM AUTHOR]

Global alcohol consumption and harmful use of alcohol is projected to increase in the coming decades, and most of the increase will occur in low- and middle-income countries (LMICs); which calls for cost-effective measures to reduce alcohol exposure in these countries. One such evidence based measure is screening and brief intervention (BI) for alcohol problems. Some of the characteristics of BI make them a particularly appealing choice of interventions in low-resource settings. However, despite evidence of effectiveness, implementation of BI in LMICs is rare. In this paper we discuss barriers to implementation of BI in LMICs, with examples from Latin America and India. Key barriers to implementation of BI in LMICs are the lack of financial and structural resources. Specialized services for alcohol use disorders are limited or non-existent. Hence primary care is often the only possible alternative to implement BI. However, health professionals in such settings generally lack training to deal with these disorders. In our review of BI research in these countries, we find some promising results, primarily in countries from Latin America, but so far there is limited research on effectiveness. Appropriate evaluation of efficacy and effectiveness of BI is undermined by lack of generalisability and methodological limitations. No systematic and scientific efforts to explore the implementation and evaluation of BI in primary and community platforms of care have been published in India. Innovative strategies need to be deployed to overcome supply side barriers related to specialist manpower shortages in LMICs. There is a growing evidence on the effectiveness of non-specialist health workers, including lay counsellors, in delivering frontline psychological interventions for a range of disorders including alcohol use disorders in LMICs. This paper is intended to stimulate discussion among researchers, practitioners and policy-makers in LMICs because increasing access to evidence based care for alcohol use disorders in LMICs would need a concerted effort from all these stakeholders. [ABSTRACT FROM AUTHOR]

Following the sudden widespread of the novel coronavirus (COVID‐19) which first appeared in Wuhan city. Remdesivir (REM) was the first medicine licensed by the US Food and Drug Administration (FDA) for COVID‐19 infected hospitalized patients. Hence, there was an urgent demand for the optimization of efficient selective and sensitive methods to be developed for the determination of REM in pharmaceuticals as well as biological samples. A sensitive and simple green spectrofluorimetric method has been developed to determine REM in pharmaceutical formulation, in addition to, spiked human plasma. The technique involves measuring the native fluorescence of REM in distilled water at 410 nm followed by excitation at 241 nm, giving a linear relationship over the range 50.00–500.00 ng/mL, and then improving the sensitivity of REM through micellar formation using 2.00% w/v sodium dodecyl sulfate (SDS). A linear relationship has been obtained over the range 10.00–350.00 ng/mL having detection and quantitation limits of 2.34 and 7.10 ng/mL, respectively. Different analytical parameters have been carefully studied. A validation study has been conducted successfully in accordance with the FDA and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The developed methods' greenness was assessed utilizing a greenness profile and analytical eco‐scale standards. Both methods were discovered to be environmentally friendly and could be successfully used for the determination of the studied drugs in pharmaceutical formulation and human plasma with good accuracy and high precision. As a result, the developed spectrofluorimetric methods could be ideally suited for determination of REM in quality control and medicinal laboratories. [ABSTRACT FROM AUTHOR]

Background: Interferon-inducible 44 like (IFI44L) is a newly discovered interferon-induced gene and has been reported to overexpress in systemic lupus erythematosus (SLE). However, little is known about the mechanism and function of IFI44L overexpression in SLE. In this study, we aimed to investigate the epigenetic mechanism of IFI44L overexpression in SLE monocyte and its potential functions contributing to the pathogenesis of SLE.Methods: We collected peripheral blood from 20 SLE patients and 20 healthy controls. Expression of IFI44L in monocytes and effects of different signal transducers and activators of transcription (STAT) pathway inhibitors on IFI44L expression were detected. Recruitment of ten-eleven translocation protein (TET) by STAT and methylation of IFI44L promoter were evaluated. Effects of IFI44L overexpression on the expression of surface markers on monocyte-derived dendritic cells (Mo-DCs) were analyzed. T cell differentiation mediated by Mo-DCs and related cytokines production were also analyzed.Results: Expression level of IFI44L was significantly increased in SLE monocyte. IFI44L expression was decreased most significantly in STAT3 inhibitor compared with other inhibitors. STAT3 regulated IFI44L expression and interacted with TET2 which induced DNA demethylation of IFI44L promoter. Overexpression of IFI44L in monocyte enhanced the maturation and functions of Mo-DC by upregulating costimulatory receptors and inducing Th1/Th17-related cytokines when cocultured with naïve CD4+ T cells.Conclusion: TET2 recruited by STAT3 induces DNA demethylation of IFI44L promoter which promotes IFI44L overexpression in monocyte contributing to the pathogenesis of SLE by enhancing the maturation and functions of Mo-DC. IFI44L is expected to become a new target for treatment of SLE. [ABSTRACT FROM AUTHOR]

Cow's milk-based infant formulas are the most common substitute to mother's milk in infancy when breastfeeding is impossible or insufficient, as cow's milk is a globally available source of mammalian proteins with high nutritional value. However, cow's milk allergy (CMA) is the most prevalent type of food allergy among infants, affecting up to 3.8% of small children. Hypoallergenic infant formulas based on hydrolysed cow's milk proteins are commercially available for the management of CMA. Yet, there is a growing demand for more options for infant feeding, both in general but especially for the prevention and management of CMA. Milk from other mammalian sources than the cow, such as goat, sheep, camel, donkey, and horse, has received some attention in the last decade due to the different protein composition profile and protein amino acid sequences, resulting in a potentially low cross-reactivity with cow's milk proteins. Recently, proteins from plant sources, such as potato, lentil, chickpeas, quinoa, in addition to soy and rice, have gained increased interest due to their climate friendly and vegan status as well as potential lower allergenicity. In this review, we provide an overview of current and potential future infant formulas and their relevance in CMA prevention and management. [ABSTRACT FROM AUTHOR]

Allergic asthma is a complex chronic inflammatory disease of the airways, driven by Th2 immune responses and characterized by eosinophilic pulmonary inflammation, airway hyperresponsiveness, excessive mucus production, and airway remodeling. Overwhelming evidence from studies in animal models and allergic asthmatic patients suggests that platelets are aberrantly activated and recruited to the lungs. It has been established that platelets can interact with other immune cells and secrete various biochemical mediators to promote allergic sensitization and airway inflammatory response, and platelet deficiency may alleviate the pathological features and symptoms of allergic asthma. However, the comprehensive roles of platelets in allergic asthma have not been fully clarified, leaving attempts to treat allergic asthma with antiplatelet agents questionable. In this review, we summarize the role of platelet activation and pulmonary accumulation in allergic asthma; emphasis is placed on the different interactions between platelets with crucial immune cell types and the contribution of platelet-derived mediators in this context. Furthermore, clinical antiplatelet approaches to treat allergic asthma are discussed. This review provides a clearer understanding of the roles of platelets in the pathogenesis of allergic asthma and could be informative in the development of novel strategies for the treatment of allergic asthma. [ABSTRACT FROM AUTHOR]

Tropomyosin (TM) is an important crustacean (Scylla paramamosain) allergen. This study aimed to assess Maillard-reacted TM (TM-G) induction of allergenic responses with cell and mouse models. We analyzed the difference of sensitization and the ability to induce immune tolerance between TM and TM-G by in vitro and in vivo models, then we compared the relationship between glycation sites of TM-G and epitopes of TM. In the in vitro assay, we discovered that the sensitization of TM-G was lower than TM, and the ability to stimulate mast cell degranulation decreased from 55.07 ± 4.23% to 27.86 ± 3.21%. In the serum of sensitized Balb/c mice, the level of specific IgE produced by TM-G sensitized mice was significantly lower than TM, and the levels of interleukins 4 and interleukins 13 produced by Th2 cells in spleen lymphocytes decreased by 82.35 ± 5.88% and 83.64 ± 9.09%, respectively. In the oral tolerance model, the ratio of Th2/Th1 decreased from 4.05 ± 0.38 to 1.69 ± 0.19. Maillard reaction masked the B cell epitopes of TM and retained some T cell epitopes. Potentially, Maillard reaction products (MRPs) can be used as tolerance inducers for allergen-specific immunotherapy. [ABSTRACT FROM AUTHOR]

Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well‐developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of (1) an intact epidermal barrier to prevent epicutaneous antigen presentation, (2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and (3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA. [ABSTRACT FROM AUTHOR]