Defensive Barrier Research Articles

The improved resistance of germinated spores to ultraviolet irradiation: Comparison with chlorine

Fungi outbreaks in water will include a series of processes, including spore aggregation, germination, biofilm, and finally present in a mixed state in the aquatic environment. More attention is paid to the control of dispersed fungal spores, however, there was little knowledge of the control of germinated spores. This study investigated the inactivation kinetics and mechanism of ultraviolet (UV) treatment for fungal spores with different germination percentages compared with dormant spores. The results indicated that the inactivation rate constants (k) of spores with 5%–45% germination were 0.0278–0.0299 cm2/mJ for Aspergillus niger and 0.0588–0.0647 cm2/mJ for Penicillium polonicum, which were lower than those of dormant spores. It suggested that germinated spores were more tolerant to UV irradiation than dormant spores, and it may be due to the defensive barrier (upregulated pigments) and some reductive substance (upregulated enoyl reductase) by absorbing UV or reacting with reactive oxygen species according to transcriptome analysis. Compared to dormant spores, the k-UV of germinated spores decreased by 18.17%–26.56% for Aspergillus niger, which was less than k-chlorine (62.33%–69.74%). A slighter decrease in k-UV showed UV irradiation can efficiently control fungi contamination, especially when dormant spores and germinated spores coexisted in actual water systems. This study indicates that more attention should be paid to germinated spores.

Ayurvedic management of Psoriasis vulgaris: A case study

Psoriasis is a Chronic, autoimmune Papulo - squamous, recurrent inflammatory disease of the skin characterised by Circumscribed, erythematous, dry, Silvery Scaley Plaques with fluctuating manifestation and frequent re-currence. patients suffering from Psoriasis experiences physical, emotional and Socioeconomic stress and embarrassment. The Incidence is about 0.4 % to 2.8 % amongst Indians and prevalence is high in third and fourth decades of life. In Ayuneda all skin Conditions are observed under 'Kushtha' where Psoriasis Can be closely correlated with Kitibha Kushtha having Vata- kapha dominance. the term 'Twacha'is derisved from the Dhatu - twacha samvarne which means body covering. It is described as upa-dhatu of Rasa dhatu and considered as one of 'Jnanendriyas' for perception of sense of touch. 'Twacha' or skin serves as barrier and first line defense against the external environmental factors. like physical, Chemical and biological assaults. The Characteistic Pathophysiological events occurring includes epidermal proliferation, Expansion of dermal Vasculature and accumulation of Inflammatory Cells. In the present study an effort has been made to treat 46 year female patient suffering from Psoriasis vulgaris Through Samshodhan and sanshaman treatment madalities described in Ayurveda. Initially Viechan chikitsa was administerd along with appropriate measures of poorva karma, and then followed by Sanshaman yoga. PASI score is used as a tool to assess the Sevirity of lesion.

Advances in the Evaluation of Gastrointestinal Absorption Considering the Mucus Layer.

Because of the increasing sophistication of formulation technology and the increasing polymerization of compounds directed toward undruggable drug targets, the influence of the mucus layer on gastrointestinal drug absorption has received renewed attention. Therefore, understanding the complex structure of the mucus layer containing highly glycosylated glycoprotein mucins, lipids bound to the mucins, and water held by glycans interacting with each other is critical. Recent advances in cell culture and engineering techniques have led to the development of evaluation systems that closely mimic the ecological environment and have been applied to the evaluation of gastrointestinal drug absorption while considering the mucus layer. This review provides a better understanding of the mucus layer components and the gastrointestinal tract's biological defense barrier, selects an assessment system for drug absorption in the mucus layer based on evaluation objectives, and discusses the overview and features of each assessment system.

Update on the skin barrier, cutaneous microbiome and host defence peptides in canine atopic dermatitis.

Canine atopic dermatitis (AD) is a complex inflammatory skin disease associated with cutaneous microbiome, immunological and skin barrier alterations. This review summarises the current evidence on skin barrier defects and on cutaneous microbiome dysfunction in canine AD. To this aim, online citation databases, abstracts and proceedings from international meetings on skin barrier and cutaneous microbiome published between 2015 and 2023 were reviewed. Since the last update on the pathogenesis of canine AD, published by the International Committee on Allergic Diseases of Animals in 2015, 49 articles have been published on skin barrier function, cutaneous/aural innate immunity and the cutaneous/aural microbiome in atopic dogs. Skin barrier dysfunction and cutaneous microbial dysbiosis are essential players in the pathogenesis of canine AD. It is still unclear if such alterations are primary or secondary to cutaneous inflammation, although some evidence supports their primary involvement in the pathogenesis of canine AD. Although many studies have been published since 2015, the understanding of the cutaneous host-microbe interaction is still unclear, as is the role that cutaneous dysbiosis plays in the development and/or worsening of canine AD. More studies are needed aiming to design new therapeutic approaches to restore the skin barrier, to increase and optimise the cutaneous natural defences, and to rebalance the cutaneous microbiome.

Linking Anthropogenic Landscape Perturbation to Herbivory and Pathogen Leaf Damage in Tropical Tree Communities.

Anthropogenic disturbance of tropical humid forests leads to habitat loss, biodiversity decline, landscape fragmentation, altered nutrient cycling and carbon sequestration, soil erosion, pest/pathogen outbreaks, among others. Nevertheless, the impact of these alterations in multitrophic interactions, including host-pathogen and vector-pathogen dynamics, is still not well understood in wild plants. This study aimed to provide insights into the main drivers for the incidence of herbivory and plant pathogen damage, specifically, into how vegetation traits at the local and landscape scale modulate such interactions. For this purpose, in the tropical forest of Calakmul (Campeche, Mexico), we characterised the foliar damage caused by herbivores and pathogens in woody vegetation of 13 sampling sites representing a gradient of forest disturbance and fragmentation in an anthropogenic landscape from well preserved to highly disturbed and fragmented areas. We also evaluated how the incidence of such damage was modulated by the vegetation and landscape attributes. We found that the incidence of damage caused by larger, mobile, generalist herbivores, was more sensitive to changes in landscape configuration, while the incidence of damage caused by small and specialised herbivores with low dispersal capacity was more influenced by vegetation and landscape composition. In relation to pathogen symptoms, the herbivore-induced foliar damage seems to be the main factor related to their incidence, indicating the enormous importance of herbivorous insects in the modulation of disease dynamics across tropical vegetation, as they could be acting as vectors and/or facilitating the entry of pathogens by breaking the foliar tissue and the plant defensive barriers. The incidence of pathogen damage also responded to vegetation structure and landscape configuration; the incidence of anthracnose, black spot, and chlorosis, for example, were favoured in sites surrounded by smaller patches and a higher edge density, as well as those with a greater aggregation of semi-evergreen forest patches. Fungal pathogens were shown to be an important cause of foliar damage for many woody species. Our results indicate that an increasing transformation and fragmentation of the tropical forest of southern Mexico could reduce the degree of specialisation in plant-herbivore interactions and enhance the proliferation of generalist herbivores (chewers and scrapers) and of mobile leaf suckers, and consequently, the proliferation of some symptoms associated with fungal pathogens such as fungus black spots and anthracnose. The symptoms associated with viral and bacterial diseases and to nutrient deficiency, such as chlorosis, could also increase in the vegetation in fragmented landscapes with important consequences in the health and productivity of wild and cultivated plant species. This is a pioneering study evaluating the effect of disturbances on multitrophic interactions, offering key insights on the main drivers of the changes in herbivory interactions and incidence of plant pathogens in tropical forests.

Uterine microbial communities and their potential role in the regulation of epithelium cell cycle and apoptosis in aged hens

BackgroundAlterations of the uterine microbiome are closely associated with various intrauterine diseases and physiological conditions, which are well-established in mammals. However, as representative oviparous animals, the research on the uterine microbial ecosystem and its functions with physiological homeostasis is limited in chickens. Additionally, continuous egg-laying disrupts the oviducal immune defenses of aged hens, susceptible to pathogen invasion, causing poor egg quality and food-borne infections in humans. Here, we investigated aging-related changes in the oviduct microbial colonization and transmission from the gut to eggs and their roles in a hen model.ResultsThe results of 16S rDNA sequencing showed significant differences in the oviduct microbial composition between young (38 weeks) and aged (77 weeks) laying hens. SourceTracker analysis further revealed differences in the effects of microbial transmission on the oviducal microbiota between young and aged hens. Enhanced barrier defense with cell apoptosis suppression and cell cycle arrest of the uterus were observed in aged hens reducing microbial transmission from the lower to upper reproductive tract. In addition, a total of 361 significantly differential metabolites were identified using metabolomics in the aged uterine microbiota, especially in products of amino acid metabolism and biosynthesis of various secondary metabolites, which might have essential effects on cell apoptosis by regulating immune responses and cell cycle. Notably, antibiotics disrupted uterine microbiota by dietary intervention and direct perfusion did not retard aging-related physiological changes but further aggravated aging processes by disrupting the cell cycle and apoptosis.ConclusionsThe microbiota continuum along the reproductive tract in aged birds differs from that in young birds, especially with a significant shift in the uterus. The aged uterine microbiota probably contributes to the regulation of cell cycle and apoptosis by microbial metabolites primarily involved in amino acid metabolism and biosynthesis of various secondary metabolites. These findings provide new insights into the roles of the reproductive tract microbiota in regulating the cell programming of the aged host, contributing to the exploration of the microbiome as a target for diagnosing aging health status and therapy for gynecological diseases in women.41Qc7p9Bx5NWR2by4xRqv2Video

An elaboration of obstacles and perspectives of medical tourism development taking the approach of integrated service provision (Case study: Isfahan Province, Iran)

Aim. The intention of the present research has been to examine and evaluate the barriers and limitations to the development of medical tourism in Isfahan as one of Iran’s tourism destinations by taking the approach of service integration.Materials and Methods. This exploratory research was conducted using mixed qualitative and quantitative methodology. Data analysis by the qualitative method was done using MAXQDA-18 software, while by the quantitative method a combination of SWOT strategic planning technique and multi-criteria decision making was usedResults. Multiple weaknesses and challenges were classified by using a framework of indexes developed on different dimensions including: quality of medical services and facilities; access to medical and tourism information; infrastructures and regulations; communications and marketing; environmental factors; treatment procedures and passive defense and international barriers. Meanwhile, the role of each of these dimensions and sub-indexes in impeding medical tourism development in the region was evaluated by examining the association between the various dimensions contributing to medical tourism development in Isfahan.Conclusions. To remove the barriers identified, several strategies are proposed. including the provision of health-based integrated services (medical, treatment and wellness), development of shared products by the sectors involved in this domain, compilation of a comprehensive plan for health tourism development, preparation of a coherent and well-organized scientific plan given the policies of resilient economy, realistic and practical attention to the branding issues, the usage of up-to-date methods of modern marketing plan for the health companies and facilitators, removal of the legal barriers to the medical tourism development and compilation of new supportive, supervisory and advertising policies.

Inhibition of EphA4 reduces vasogenic edema after experimental stroke in mice by protecting the blood-brain barrier integrity

Cerebral vasogenic edema, a severe complication of ischemic stroke, aggravates neurological deficits. However, therapeutics to reduce cerebral edema still represent a significant unmet medical need. Brain microvascular endothelial cells (BMECs), vital for maintaining the blood-brain barrier (BBB), represent the first defense barrier for vasogenic edema. Here, we analyzed the proteomic profiles of the cultured mouse BMECs during oxygen-glucose deprivation and reperfusion (OGD/R). Besides the extensively altered cytoskeletal proteins, ephrin type-A receptor 4 (EphA4) expressions and its activated phosphorylated form p-EphA4 were significantly increased. Blocking EphA4 using EphA4-Fc, a specific and well-tolerated inhibitor shown in our ongoing human phase I trial, effectively reduced OGD/R-induced BMECs contraction and tight junction damage. EphA4-Fc did not protect OGD/R-induced neuronal and astrocytic death. However, administration of EphA4-Fc, before or after the onset of transient middle cerebral artery occlusion (tMCAO), reduced brain edema by about 50%, leading to improved neurological function recovery. The BBB permeability test also confirmed that cerebral BBB integrity was well maintained in tMCAO brains treated with EphA4-Fc. Therefore, EphA4 was critical in signaling BMECs-mediated BBB breakdown and vasogenic edema during cerebral ischemia. EphA4-Fc is promising for the treatment of clinical post-stroke edema.

Effects of nutritional therapy on gastrointestinal microbial digestion and barrier defense markers in elderly patients with diabetes.

We sought to investigate the effects of gastrointestinal nutrition therapy on gastrointestinal microbial digestion and barrier defense markers in elderly patients with diabetes. A total of 120 elderly patients with type 2 diabetes were enrolled at our hospital between January 2020 and December 2022. The participants in this study were randomly allocated into either the nutritional group (n = 60) who underwent gastrointestinal nutrition therapy or the control group (n = 60) who underwent conventional T2DM diet management for a period of 12weeks. Clinical data, as well as small intestinal permeability measured by the lactulose-mannitol urine test, plasma circulating IL-6 and zonulin levels measured by ELISA, and expressions of ZO-1 and Claudin-3 in blood analyzed through Western blotting were collected. The nutrition group demonstrated a higher proportion of patients achieving HbA1c < 7% compared to the control group (P < 0.05). Moreover, the nutrition group exhibited a greater reduction in fasting and postprandial blood glucose levels compared to the control group (P < 0.05). The concentrations of formate-tetrahydrofolate ligase and acetic CoA transferase were significantly increased in the nutrition group compared to the control group (P < 0.05). Fecal analysis revealed higher levels of acetic acid and butyric acid in the nutrition group compared to the control group (P < 0.05). The ratio of lactulose to mannitol was higher in the nutrition group compared to the control group (P < 0.05). Furthermore, the nutrition group showed lower levels of IL-6 and zonulin compared to the control group (P < 0.05). Personalized gastrointestinal nutrition therapy was found to enhance the production of short-chain fatty acids and preserve intestinal permeability, leading to improved gastrointestinal microbial digestion and barrier defense in elderly patients with diabetes.

Displacement, Out-of-placeness, and urban research in the south: An experiential perspective

Interdisciplinary engagements encounter a significant challenge in surmounting defensive barriers within conventional urban research. This emphasizes the necessity of creating space for comprehensive dialogs to tackle pivotal issues related to social justice in urban practice and academia. Urban research in the global south mandates a specific perspective that extends beyond the common oversight and veiling of specific viewpoints and encounters. Black geographies offers a language that acknowledges experiential, ingrained, and incarnate realities, contexts, and expressions of urbanization that surpass materiality. By extension, and as Bloch and Meyer argue, it expands the scope of contemplation to contemporary themes such as displacement.

Matrix metalloproteinase 2 contributes to adult eclosion and immune response in the small hive beetle, Aethina tumida.

During the pupal-adult eclosion process of holometabolous insects, the old cuticle is shed and replaced by a completely different new cuticle that requires tanning and expansion, along with extensive extracellular matrix (ECM) remodeling. In vertebrates, matrix metalloproteinases (MMPs), a class of zinc-dependent endopeptidases, play key roles in regulating the ECM that surrounds cells. However, little is known about these extracellular proteinases available in insects. The small hive beetle (SHB), Aethina tumida, is a widespread invasive parasite of honey bees. In this study, 6 MMP homologs were identified in the SHB genome. RNA interference experiments showed that all 6 AtMmps are not required for the larval-pupal transition, only AtMmp2 was essential for pupal-adult eclosion in SHB. Knockdown of AtMmp2 resulted in eclosion defects and wing expansion failure, as well as mortality within 3d of adult eclosion. Transcriptomic analysis revealed that knockdown of AtMmp2 significantly increased expression of the Toll and Imd pathways, chitin metabolism, and cross-linking (such as the pro-phenoloxidase activating cascade pathway and the tyrosine-mediated cuticle sclerotization and pigmentation pathway). These data revealed evolutionarily conserved functions of Mmp2 in controlling adult eclosion and wing expansion, also provided a preliminary exploration of the novel function of regulating Toll and Imd pathways, as well as new insights into how MMPs regulate insect development and defense barriers.

IL-22: Immunity's bittersweet symphony.

Epithelial cells play a crucial role in barrier defense. Here, Moniruzzaman et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230106) discovered that interleukin-22 (IL-22) represses MHC class II expression by epithelial cells with an opposite impact on chronic inflammatory disease and viral infection.

Tumor necrosis factor α2 (TNFα2) facilitates gut barrier breach by Aeromonas hydrophila and exacerbates liver injury in hybrid fish

TNFα is a multifunctional cytokine that can modulate immune homeostasis and promote cellular regulation in mammals, but the crucial role of TNFα in fish gut remained unclear. The current study aimed to evaluate the immunoregulatory function of TNFα2 on gut barrier breach by A. hydrophila and systemic pathogenesis in gut and liver of WR (White crucian carp ♀ × red crucian carp ♂). WR-TNFα2 encoded 232 amino acid residues and showed a high-level of WR-TNFα2 expression in spleen. After A. hydrophila and lipopolysaccharide (LPS) stimulated, elevated levels of WR-TNFα2 expressions were detected in immune-related tissues and cultured fish cells, respectively. Gut perfusion with WR-TNFα2 alone could alter antioxidant status, increase extrinsic apoptosis as well as promote inflammatory response in midgut, causing severe injury of epithelial barrier. Moreover, WR-TNFα2-treated midgut exhibited a decline of mucosal protection against invasive A. hydrophila, which could elevate bacterial burden in tissues, aggravate tissue injury as well as attenuate immune activation. Our results suggested that WR-TNFα2 could exhibit a detrimental effect on gut barrier defense against A. hydrophila infection and dysregulate immune response in midgut and liver of hybrid crucian carp.

Characterization of biochemical properties of the skin mucus of turbot (Scophthalmus maximu) and differential proteomic analysis of skin mucus in response to Vibrio anguillarum

Fish mucus is the first defensive barrier to fight off pathogens in teleosts. In this study, we reported the antibacterial activity of turbot (Scophthalmus maximus) skin mucus, and the results showed that mucus exhibited antibacterial effects against both Gram-positive and Gram-negative bacteria. Moreover, biochemical parameters assays suggested that turbot skin mucus exhibited strong total antioxidant capacity (TAC), protease activity and lysozyme activity. To explore the roles of skin mucus in defense against pathogens, we processed proteomic profiling of turbot skin mucus before and after Vibrio anguillarum infection by LC-MS/MS approach. Differentially expressed proteins (DEPs) were identified among V. anguillarum treated turbot skin mucus at 0 h, 4 h and 48 h post-infection, respectively. A total of 3,324,612 secondary spectrograms were obtained, containing 38,681 unique peptides which were corresponded to 4987 proteins. The DEPs were markedly enriched in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with immunity, biological adhesion and cell junction, revealing complex changes of turbot skin mucus during pathogens infection. Collectively, this study can help us better understand the characteristics of turbot skin mucus in infection immunity and the biological function of skin mucus in response to bacterial invasion.

Single-cell transcriptional profiling reveals immunomodulatory properties of stromal and epithelial cells in periodontal immune milieu with diabetes in rats

Periodontitis is the sixth major complication of diabetes. Gingiva, as an important component of periodontal tissues, serves as the first defense barrier against infectious stimuli. However, relatively little is known about cellular heterogeneity and cell-specific changes in gingiva in response to diabetes-associated periodontitis. To characterize molecular changes linking diabetes with periodontitis, we profiled single-cell transcriptome analyses of a total of 45,259 cells from rat gingiva with periodontitis under normoglycemic and diabetic condition. The single-cell profiling revealed that stromal and epithelial cells of gingiva contained inflammation-related subclusters enriched in functions of immune cell recruitment. Compared to normoglycemic condition, diabetes led to a reduction in epithelial basal cells, fibroblasts and smooth muscle cells in gingiva with periodontitis. Analysis of differentially expressed genes indicated that stromal and epithelial populations were reprogrammed towards pro-inflammatory phenotypes promoting immune cell recruitment in diabetes-related periodontitis. In aspect of immune cells, diabetes prominently enhanced neutrophil and M1 macrophage infiltration in periodontitis lesions. Cell-cell communications revealed enhanced crosstalk between stromal/epithelial cells and immune cells mediating by chemokine/chemokine receptor interplay in diabetes-associated periodontitis. Our findings deconvolved cellular heterogeneity of rat gingiva associated with periodontitis and diabetes, uncovered altered immune milieu caused by the disease, and revealed immunomodulatory functions of stromal and epithelial cells in gingival immune niche. The present study improves the understanding of the link between the diabetes and periodontitis and helps in formulating precise therapeutic strategies for diabetes-enhanced periodontitis.

Sex-Dependent Skin Aging and Rejuvenation Strategies

The skin, the largest external organ, serves as the primary defensive barrier against various environmental factors such as ultraviolet exposure, pollution, dietary habits, pathogens, and chemical compounds. Consequently, the skin reflects our age through visible signs of aging, such as wrinkles, age spots, dullness, and sagging. This review explores the gender-related aspects of cutaneous aging and the associated dermatological conditions. It highlights the different manifestations of aging in females and males that become evident after the age of 12, emphasizing the susceptibility to conditions such as seborrheic eczema, acne, and rosacea. Treatment strategies often vary between genders due to these disparities. While men tend to experience accelerated skin aging, most anti-aging products and strategies primarily target females. However, there has been a recent shift in men’s priorities, leading to increased interest in maintaining a youthful appearance and seeking cosmetic treatments. The manuscript covers a comprehensive range of modern dermal anti-aging and rejuvenation procedures, including plastic surgery, bio-revitalization methods, lasers, microneedling, and topical treatments. Additionally, it explores promising natural and synthetic therapeutics for combating age-related skin changes. The focus is on understanding the physiological aspects of gender-related cutaneous structure and aging to guide effective and tailored approaches in dermatological practice.

The therapeutic effect of tanshinone IIA in mouse astrocytes after treatment with Angiostrongylus cantonensis fifth-stage larval excretory-secretory products.

Angiostrongylus cantonensis is an important food-borne zoonotic parasite that causes eosinophilic meningitis and meningoencephalitis in humans. Excretory-secretory products (ESPs) are valuable targets for studying host-parasite relationships. ESPs are composed of a variety of molecules that are used to penetrate defensive barriers and avoid immune attack of the host. Tanshinone IIA (TSIIA) is a vasoactive cardioprotective drug that is widely used in studies evaluating potential therapeutic mechanisms. In this study, we will evaluate the therapeutic effects of TSIIA in mouse astrocytes after A. cantonensis fifth-stage larvae (L5) ESPs treatment. Here, we examined the therapeutic effect of TSIIA by real-time qPCR, western blotting, activity assay, and cell viability assays. First, the results showed that TSIIA can elevate cell viability in astrocytes after stimulation with ESPs. On the other hand, TSIIA downregulated the expression of apoptosis-related molecules. However, the expression of molecules related to antioxidant, autophagy, and endoplasmic reticulum stress was significantly increased. The results of antioxidant activation assays showed that the activities of superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase were significantly increased. Finally, we found that cell apoptosis and oxidative stress were reduced in TSIIA-treated astrocytes by immunofluorescence staining. The findings from this study suggest that TSIIA can reduce cellular damage caused by A. cantonensis L5 ESPs in astrocytes and clarify the related molecular mechanisms.

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia.

Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination. Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides. Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors. In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.

Secretory leukocyte protease inhibitor modulates FcεRI-dependent but not Mrgprb2-dependent mastocyte function in psoriasis

Psoriasis, which involves mast cells, is a chronic inflammatory skin disorder whose pathophysiology is still not fully understood. We investigated the role of secretory leukocyte protease inhibitor (SLPI), a potential inhibitor of mastocyte serine proteases, on mast cell-dependent processes of relevance to the skin barrier defense in psoriasis. Here, we demonstrate that the dermal mast cells of patients with psoriasis express SLPI but not those of healthy donors. Moreover, SLPI transcripts were found to be markedly upregulated in murine mast cells by mediators derived from psoriasis skin explant cultures. Using mast cells from SLPI-deficient mice and their SLPI+ wild-type controls, we show that SLPI inhibits the activity of serine protease chymase in mastocytes. SLPI was also found to enhance the degranulation of mast cells activated via anti-IgE Abs but not Mrgprb2 ligands. Finally, we demonstrate that the expression and function of Mrgprb2 in mast cells are suppressed by a normal and, to a larger extent, psoriatic skin environment. Together, these findings reveal mechanisms underlying FcεRI– and Mrgprb2-dependent mast cell function that have not been described previously.

Effects and Underlying Mechanisms of Zearalenone Mycotoxin at Concentrations Close to the EC Recommendation on the Colon of Piglets after Weaning

Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi that contaminates food and feed, affecting both human and animal health. Among farm animals, the pig is a great consumer of grains and has a native sensitivity to mycotoxins. As the main route of contamination is oral, the intestine is the first defense barrier that plays an important role in the immune response being able to secrete effector molecules (cytokines). At the European level, there are no regulations regarding the amount of ZEN that can be present in the feed of piglets, only recommendations for piglets 0.100 mg ZEN/kg feed (100 ppb). In this study, the effects of ZEN in concentrations below (75 ppb) and above (290 ppb) EU recommendation on the level of some key markers involved in the oxidative and inflammatory response, as well as the mechanisms and signaling pathways through which ZEN could produce its toxicity, were monitored in the colon of weaned piglets. The exposure of the piglets to the lower concentration of ZEN (75 ppb) did not lead to changes in stress and inflammation markers or in the signaling pathways associated with these processes.