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PLoS Pathogens May 2024The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to...
The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg "losers" carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped "losers" instead of migrating intestinal "winners". This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite's eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized.
PubMed: 38814989
DOI: 10.1371/journal.ppat.1012268 -
PloS One 2024The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was... (Comparative Study)
Comparative Study
The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.
Topics: Animals; Dogs; Cytokines; Dog Diseases; Anal Sacs; Male; Microbiota; Female; RNA, Ribosomal, 16S; Dermatitis, Atopic; Case-Control Studies; Bacteria
PubMed: 38814946
DOI: 10.1371/journal.pone.0298361 -
Turkish Journal of Medical Sciences 2023is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to pollen, which is not native to Anatolia.
BACKGROUND/AIM
is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to pollen, which is not native to Anatolia.
MATERIALS AND METHODS
Patients aged 5-18 years who underwent respiratory allergy screening in Türkiye's largest referral center over a 1-year period were reviewed retrospectively for a diagnostic study of allergy.
RESULTS
Of 246 patients, 207 (67.6% male) with a median age of 11.7 (IQR 9.2-15) years were found to be aeroallergen-sensitive and (32%) was the second most common sensitivity after grass pollen (83.6%). In the -sensitive subgroup, only 3% (2/67) were monosensitive, and grass (77.6%), cat (38.8%), and weeds (38.8%) were the most common co-sensitivities. Cup a 1 specific IgE (sIgE) was measured in 26 patients with sensitivity and all were found to be positive. A nasal allergen challenge (NAC) was performed for 44 of 67 patients with sensitivity, and 13 of 44 patients had a positive outcome (NAC+) at the highest two extract concentrations. The wheal sizes and Cup a 1 sIgE levels of the NAC+ subgroup were higher than those of the NAC- subgroup but reached significance only for wheal size [6 (5-7.5) vs. 4.5 (4-6), p=0.004]. The NAC+ subgroup reported more frequent nasal discharge, congestion, and eye symptoms than the NAC- subgroup during the relevant pollen season.
CONCLUSION
sensitivity has increased in the East Mediterranean region, similarly to North Mediterranean data, and this is associated with the presence of allergy both clinically and in laboratory findings. should be included in the aeroallergen screening panels of children from the East Mediterranean.
Topics: Humans; Child; Male; Female; Adolescent; Cupressus; Allergens; Retrospective Studies; Child, Preschool; Pollen; Turkey; Immunoglobulin E; Rhinitis, Allergic, Seasonal; Mediterranean Region
PubMed: 38813017
DOI: 10.55730/1300-0144.5692 -
Frontiers in Allergy 2024The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously... (Review)
Review
The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.
PubMed: 38812719
DOI: 10.3389/falgy.2024.1404735 -
Frontiers in Immunology 2024Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1... (Review)
Review
Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter- and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site.
Topics: Humans; Mast Cells; Cell Degranulation; Bradykinin; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Animals; Angioedema; Nerve Tissue Proteins; Kallikrein-Kinin System
PubMed: 38812508
DOI: 10.3389/fimmu.2024.1399459 -
Frontiers in Bioscience (Landmark... May 2024, a Gram-positive bacterium, is a prominent foodborne pathogen that causes listeriosis and poses substantial health hazards worldwide. The continuing risk of listeriosis...
BACKGROUND
, a Gram-positive bacterium, is a prominent foodborne pathogen that causes listeriosis and poses substantial health hazards worldwide. The continuing risk of listeriosis outbreaks underlies the importance of designing an effective prevention strategy and developing a robust immune response by reverse vaccinology approaches. This study aimed to provide a critical approach for developing a potent multiepitope vaccine against this foodborne disease.
METHODS
A chimeric peptide construct containing 5 B-cell epitopes, 16 major histocompatibility complex I (MHC-I) epitopes, and 18 MHC-II epitopes were used to create a subunit vaccination against . The vaccine safety was evaluated by several online methods, and molecular docking was performed using ClusPro to determine the binding affinity. Immune simulation was performed using the C-ImmSimm server to demonstrate the immune response.
RESULTS
The results validated the antigenicity, non-allergenicity, and nontoxicity of the chimeric peptide construct, confirming its suitability as a subunit vaccine. Molecular docking showed a good score of 1276.5 and molecular dynamics simulations confirmed the construct's efficacy, demonstrating its promise as a good candidate for listeriosis prophylaxis. The population coverage was as high as 91.04% with a good immune response, indicating good antigen presentation with dendritic cells and production of memory cells.
CONCLUSIONS
The findings of this study highlight the potential of the designed chimeric peptide construct as an effective subunit vaccine against , paving the way for future advances in preventive methods and vaccine design.
Topics: Listeria monocytogenes; Molecular Docking Simulation; Bacterial Vaccines; Vaccines, Subunit; Listeriosis; Computational Biology; Epitopes, B-Lymphocyte; Humans; Epitopes; Molecular Dynamics Simulation; Animals; Foodborne Diseases; Immunoinformatics
PubMed: 38812301
DOI: 10.31083/j.fbl2905176 -
Dermatology Practical & Conceptual Apr 2024Increasing the numbers of patch testing in suspected children increases the rate of diagnosis of allergic contact dermatitis and the identification of clinically...
INTRODUCTION
Increasing the numbers of patch testing in suspected children increases the rate of diagnosis of allergic contact dermatitis and the identification of clinically relevant allergens.
OBJECTIVE
The aim of this study was to identify the most frequently observed allergens among Turkish children and adolescents patch-tested in 2013-2023.
METHODS
The patch test results of 160 patients (age ≤18) were analyzed retrospectively. The frequency of contact allergens and distribution of positive results in terms of sex, age group (children and adolescents), and the presence of atopic dermatitis (AD) were identified.
RESULTS
Forty-nine patients (30.6%) (34 girls and 15 boys) exhibited positive patch test reactions to a minimum of one allergen, and contact sensitivity was statistically significantly higher in girls (P=0.034). The five most frequent allergens were nickel sulfate (10.6%), MCI/MI (8.1%), cobalt chloride (5.6%), p-phenylenediamine (PPD) (5%), and MI (3.5%). No significant association was observed between patch test positivity and age groups (P>.05). Nickel sulfate sensitivity was significantly higher in girls than in boys (P=.043). A positive reaction was detected in 31.3% of patients with AD and in 33.7% of those without (P>.05), and a statistically significant relationship was observed between contact sensitivity to fragrance allergens and AD (P=.046).
CONCLUSION
Metals and preservatives represent the most frequent allergens in Turkish children and adolescents. Metal sensitivity is expected to decrease as legislation is enforced. Regulatory measures are now required to reduce MI and MCI/MI contact allergy in Turkey.
PubMed: 38810081
DOI: 10.5826/dpc.1402a151 -
Frontiers in Immunology 2024Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy,...
Bronchom assuages airway hyperresponsiveness in house dust mite-induced mouse model of allergic asthma and moderates goblet cell metaplasia, sub-epithelial fibrosis along with changes in Th2 cytokines and chemokines.
BACKGROUND
Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy, leading to a poorly-controlled disease state, necessitating the development of novel therapies. Bronchom is a calcio-herbal formulation, which is purported to treat chronic asthma. The objective of the current study was to examine the in-vivo efficacy of Bronchom in mouse model of allergic asthma.
METHODS
Ultra high performance liquid chromatography was utilized to analyze the phytocompounds in Bronchom. Further, the in-vivo efficacy of Bronchom was evaluated in House dust mite (HDM)-induced allergic asthma in mice. Mice were challenged with aerosolized methacholine to assess airway hyperresponsiveness. Subsequently, inflammatory cell influx was evaluated in bronchoalveolar lavage fluid (BALF) followed by lung histology, wherein airway remodeling features were studied. Simultaneously, the levels of Th2 cytokines and chemokines in the BALF was also evaluated. Additionally, the mRNA expression of pro-inflammatory and Th2 cytokines was also assessed in the lung along with the oxidative stress markers.
RESULTS
Phytocompounds present in Bronchom included, gallic acid, protocatechuic acid, methyl gallate, rosmarinic acid, glycyrrhizin, eugenol, 6-gingerol and piperine. Bronchom effectively suppressed HDM-induced airway hyperresponsiveness along with the influx of leukocytes in the BALF. Additionally, Bronchom reduced the infiltration of inflammatory cells in the lung and it also ameliorated goblet cell metaplasia, sub-epithelial fibrosis and increase in α-smooth muscle actin. Bronchom decreased Th2 cytokines (IL-4 and IL-5) and chemokines (Eotaxin and IP-10) in the BALF. Likewise, it could also suppress the mRNA expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6 and IL-33), and IL-13. Moreover, Bronchom restored the HDM-induced diminution of endogenous anti-oxidants (GSH and SOD) and the increase in pro-oxidants (GSSG and MDA). Furthermore, Bronchom could also decrease the nitrosative stress by lowering the observed increase in nitrite levels.
CONCLUSION
Taken together, the results of the present study data convincingly demonstrate that Bronchom exhibits pharmacological effects in an animal model of allergic asthma. Bronchom mitigated airway hyperresponsiveness, inflammation and airway remodeling evoked by a clinically relevant allergen and accordingly it possesses therapeutic potential for the treatment of asthma.
Topics: Animals; Asthma; Mice; Disease Models, Animal; Cytokines; Goblet Cells; Metaplasia; Pyroglyphidae; Th2 Cells; Chemokines; Fibrosis; Mice, Inbred BALB C; Airway Remodeling; Female; Plant Extracts; Lung
PubMed: 38807596
DOI: 10.3389/fimmu.2024.1384697 -
Plant Disease May 2024Polygonatum kingianum is a Chinese herbal medicine that belongs to the genus Polygonatum of the family Liliaceae. In June 2023, Polygonatum kingianum Coll. et Hemsl. in...
Polygonatum kingianum is a Chinese herbal medicine that belongs to the genus Polygonatum of the family Liliaceae. In June 2023, Polygonatum kingianum Coll. et Hemsl. in nurseries in Qujing, Yunnan Province, China, showed irregular brown spots on the leaves, whole leaf necrosis, and plant death in serious cases, with an incidence of 10-20% (Fig. S1). To identify the pathogens of P. kingianum, six diseased samples were collected from nurseries with 0.6 acre. These diseased sample leaves were soaked in 0.1% HgCl2 for 1 min and 75% ethanol for 2 min and then rinsed thrice with sterile water. Treated leaves were cut into small pieces (5×5 mm) and cultured on potato dextrose agar (PDA) for five days at 28°C. Total thirteen fungal strains were isolated from PDA medium. The nuclear ribosomal internal transcribed spacer of ribosomal DNA (ITS rDNA) region of these 13 strains was amplified by polymerase chain reaction (PCR) using universal primers ITSI/ITS4 (White et al. 1990). Sequencing and BLAST of the ITS region on NCBI showed that 11 out of 13 fungal strains belonged to the genus Alternaria, with an identity ≥99%. We selected one of the Alternaria strains, HJ-A1, for further study. The HJ-A1 colony appeared grayish brown white-to-gray with a flocculent texture on the front side and a dark gray underside on the PDA medium (Fig. S1). The conidiophores appeared brown, either single or branched, and produced numerous short conidial chains. The conidia were obclavate to obpyriform or ellipsoid in shape and contained 1-4 transverse septa and 0-2 oblique septa. The conidial diameter was 27.30µm in length and 12.27µm in width. (Fig. S1). To further determine the species of HJA1, the genomic DNA of HJ-A1 was extracted using the Lysis Buffer for PCR (AG, Hunan, China). Four Alternaria genomic DNA regions including the ITS, translation elongation factor 1-α gene (TEF1-α), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and Alternaria major allergen gene (Alt a1) were amplified by PCR using the primers as previously reported (Woudenberg et al. 2013, Hong et al. 2005). Sequence analysis revealed that the ITS (484bp) of HJ-A1 (NCBI No. PP082633), TEF1-α (267bp) of HJ-A1 (NCBI No. PP419893), GAPDH (582bp) of HJ-A1 (NCBI No. PP419892), and Alt a1 (522bp) of HJ-A1 (NCBI No. PP228046) shared the highest identity with A. alternata respectively (99≥%). A maximum likelihood phylogenetic tree was constructed with the combined sequence data sets of ITS, GAPDH, TEF, and Alt a1 using MEGA 7. The results showed that HJ-A1 strain clustered with A. alternate (Fig. S2). The pathogenicity of HJ-A1 was tested according to Koch's postulates by inoculating HJ-A1 conidia suspension (2×105 conidia/mL) into leaves of 1-year-old P. kingianum, with sterile water as a control. Each treatment group included 3 plants with 3 replicates. The tested plants were planted in a phytotron at 28℃ and 90% humidity. Three days after inoculation, symptoms similar to those under natural conditions were observed in the HJ-A1-inoculated plants, whereas no symptoms were observed in the control plants (Fig. S1). The same fungal strains were re-isolated from inoculated leaves and identified by morphologically and sequence of ITS. Previous studies showed that Alternaria alternata funji cause many plant diseases, such as fig fruit rot (Latinović N et al. 2014),daylily leaf spot (Huang D et al. 2022), fruit blight on sesame (Cheng H et al. 2021),leaf spot of Cynanchum atratum Bunge (Sun H et al. 2021) and so on. To our knowledge, this is the first report of A. alternata causing P. kingianum leaf spot in China. The discovery of this pathogen will help to guide the protection and control of P. kingianum disease.
PubMed: 38803070
DOI: 10.1094/PDIS-03-24-0597-PDN -
Journal of Cellular and Molecular... May 2024The current era we experience is full with pandemic infectious agents that no longer threatens the major local source but the whole globe. Almost the most emerging...
The current era we experience is full with pandemic infectious agents that no longer threatens the major local source but the whole globe. Almost the most emerging infectious agents are severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), followed by monkeypox virus (MPXV). Since no approved antiviral drugs nor licensed active vaccines are yet available, we aimed to utilize immunoinformatics approach to design chimeric vaccine against the two mentioned viruses. This is the first study to deal with design divalent vaccine against SARS-CoV-2 and MPXV. ORF8, E and M proteins from Omicron SARS-CoV-2 and gp182 from MPXV were used as the protein precursor from which multi-epitopes (inducing B-cell, helper T cells, cytotoxic T cells and interferon-ɣ) chimeric vaccine was contrived. The structure of the vaccine construct was predicted, validated, and docked to toll-like receptor-2 (TLR-2). Moreover, its sequence was also used to examine the immune simulation profile and was then inserted into the pET-28a plasmid for in silico cloning. The vaccine construct was probable antigen (0.543) and safe (non-allergen) with strong binding energy to TLR-2 (-1169.8 kcal/mol) and found to have significant immune simulation profile. In conclusion, the designed chimeric vaccine was potent and safe against SARS-CoV-2 and MPXV, which deserves further consideration.
Topics: SARS-CoV-2; Humans; COVID-19; COVID-19 Vaccines; Molecular Docking Simulation; Toll-Like Receptor 2; Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte; Epitopes
PubMed: 38801408
DOI: 10.1111/jcmm.18452