Allergic Research Articles

Isotype diversity of antibodies specific for component allergens in the context of allergic diseases: eosinophilic esophagitis (EoE), asthma, and the alpha-gal syndrome (AGS)

From the earliest days of studying the reagins in allergic sera that give rise to the Prausnitz-Kuestner reaction, there was evidence that there were other types of antibodies (Ab) specific for allergens, particularly those induced by immunotherapy. By 1980, not only was IgE recognized and could be measured, but the presence of other isotypes including IgG and IgA in patients with IgE was well established. From that time onwards the development of monoclonal antibodies made it possible to distinguish and measure antibodies of other isotypes such as IgG4, IgG2, and IgG3. Over the past 40 years two things have dominated the field- firstly, the techniques for measuring isotype specific antibodies to allergens have improved steadily. Secondly, several different allergic diseases or phenomena have been identified in which isotype diversity of the antibodies has become a major issue. Prior to 1990 only occasional cases of eosinophilic esophagitis (EoE) had been identified, but since then they have become common. Most of the cases have positive skin tests and/or IgE Ab to cow's milk or wheat, but it became obvious that most cases of EoE are not primarily related to IgE. Today it is clear that IgG4 Ab to these allergens play a significant role in cases of EoE. In 2000 the first reports of children developing tolerance to cat allergen appeared. Today it is clear that this tolerance depends on high levels of IgG4 antibodies and there is increasing evidence that the IgG4 response is primarily against Fel d 1. The most recent novel allergic disease is the alpha-gal syndrome (AGS). This condition is based on IgE antibodies specific for the oligosaccharide galactose alpha,1-3-galactose, which are primarily induced by tick bites. However, in this case it was already well known that all immunocompetent primates have made IgG and IgM antibodies to this oligosaccharide. Furthermore, it is not clear whether the IgG isotypes, particularly IgG1 and IgG3, play a role in the inflammatory response to the oligosaccharide. Overall, it is clear that current and future investigation of allergic diseases requires careful assessment of allergen specific antibodies of diverse isotypes in addition to IgE.

Eosinophil-derived neurotoxin levels can predict allergic disease development and atopic march in children.

In some children, atopic manifestations begin with atopic dermatitis and progress to allergic asthma and allergic rhinitis; of them, a small subset experience food allergies as well. This progression shares genetic and environmental predisposing factors and immunological features, such as allergen-specific T helper type 2 responses, that manifest as specific immunoglobulin E production and eosinophil activation. Eosinophil-derived neurotoxin (EDN), which is released by eosinophils during this activation, shows promise as a reliable and accurate biomarker. EDN levels are elevated in a subset of patients with atopic march-associated conditions. Elevated EDN levels predict allergic disease development, demonstrating that EDN is a good biomarker for the prognosis, diagnosis, treatment, and monitoring of allergic diseases comprising atopic march. The early measurement of EDN would help identify those who are more likely to develop allergic diseases later in life. Thus, the early detection and treatment of elevated EDN could lead to better outcomes, including halting atopic march.

Unusual ascites following ingestion of spicy food in a young woman.

Eosinophilic enteritis, one type of eosinophilic disorders, is a rare disease characterised by infiltration of the small bowel with numerous mucosal eosinophils or/and eosinophilic ascites pathologically. The prevalence of eosinophilic enteritis is fewer than ten in100,000 people, frequently occurred in female1. The pathogenesis of the disease is poorly known, but allergic diseases, autoimmune connective reaction and intestinal dysbiosis have been implicated.

A Phenotypically Distinct Human Th2 Cell Subpopulation Is Associated With Development of Allergic Disorders in Infancy.

Little is known about the ontogeny of T cell immunity during infancy in farming and urban lifestyles due to the lack of immunophenotyping in such birth cohorts. Two birth cohorts (farming and urban) at differing risks and rates of allergic diseases were compared. Blood mononuclear cells were collected from infants at birth, and 6 and 12 months of age. Full spectrum flow cytometry, followed by traditional gating and the Scalable Weighted Iterative Flow-clustering Technique (SWIFT) high-dimensional analysis, were used to identify cell populations that differed between farming and urban infants. Additionally, single-cell RNAseq and multiplex cytokine assays were used to assess the function of cell populations of interest. Several regulatory T cell (Treg) subpopulations were elevated in farming lifestyles and in non-atopic infants. A unique effector memory CD25+CD127+CD161-CD49d+CCR4+CRTH2+ Th2 population was elevated at 6 months in urban infants and in those who developed atopic dermatitis and/or food allergy and allergic sensitization. Although this population shared Th2 and IL-9 skewing with Th2A cells, the population uniquely failed to express CD161, produced more IL-2 and TNF-α, and upregulated the differentially expressed genes (DEGs), FOXP3 and the cytokine inducible SH2-containing protein gene (CISH) relative to Th2A cells. This population has been termed Th2B cells. We describe a unique effector memory Th2 population elevated in urban high-risk infants, potentially implicated in the development of allergic disease.

Is AIT worth your while? Economic evaluation of allergen-specific immunotherapy (AIT) for otorhinolaryngologists in private practice

The burden of allergic diseases is significant for patients, payers in the healthcare system, and the political economy. Numerous studies have demonstrated the efficacy and cost-effectiveness of allergen immunotherapy (AIT) compared to symptomatic treatments. However, allergic patients in Germany often do not receive adequate treatment. This study aims to investigate the reimbursement of allergy diagnostics and AIT for ear, nose, and throat (ENT) physicians in private practice. Amodel calculation was conducted to assess the reimbursement of allergology services across 12statutory health insurance associations (Kassenärztliche Vereinigungen, KV) based on the Physician Fee Schedule (Einheitlicher Bewertungsmaßstab, EBM) and KV-specific regulations for the year 2022 [20, 22]. Reimbursement was calculated according to EBM values and with areduced point value. Quarterly reimbursement for a3-year therapy and hourly rates for subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) were analyzed and compared with the average reimbursement per case (durchschnittlicher Honorarumsatz je Behandlungsfall, DHPB). Adherence to the budget resulted in ENT physicians being reimbursed above the DHPB for SCIT in every KV. This remained true for most KVs, even when the excess to the case value was only rewarded at 15%. Reimbursement for a3-year SLIT was lower than the DHPB across all KVs. Allergy diagnostics and AIT represent economically advantageous options for ENT practices. Maintenance therapy demonstrates apositive cost-benefit ratio, supporting the call for aconsistent 3‑year treatment regimen.

Risk of postpartum depression in women with allergic disorders: A nationwide cohort study involving 1,017,507 women

BackgroundAllergic symptoms and depression are prevalent ailments in childbearing age women. This study assessed the risk of maternal postpartum depression (PPD) associated with prenatal allergic disorders. MethodsFrom 1,017,507 eligible women of 20–49 years old with singleton live births and 20-week or more gestational age in the birth registry of Taiwan, from 2011 to 2020, we identified cohorts with and without allergic disorders matched by propensity score in the size of 457,826. Cumulative incident PPDs in one year after births were assessed from insurance claims data. Odds ratios (OR) of PPD were measured by each allergic type and multiple types, comparing with the controls. ResultsWith an overall cumulative PPD incidence 1.25-fold higher in the allergic cohort than in the controls (0.69 % versus 0.55 %), the rate was the highest in women with asthma: 0.94 % with an adjusted OR of 1.71 (95 % CI = 1.49–1.95), followed by those with allergic rhinitis, allergic conjunctivitis and atopic dermatitis. The rate increased from 0.65 % for those with one allergic disorder to 1.06 % for those with 4 or 5 disorders, and the corresponding adjusted OR increased from 1.17 (95 % CI = 1.10–1.24) to 1.92 (95 % CI = 1.36–2.69). LimitationThe claims data lack detailed information on socio-demographic status, lifestyle, laboratory result, physical activity, and family medical history. ConclusionsWomen with prenatal allergic disorder(s) are at an increased risk of PPD in addition to the impact of pregnancy. Prompt and efficient intervention for PPD prevention is needed for women with allergic disorders, particularly for those with asthma and multiple disorders.

Childhood allergy and anxiety/depression in early adulthood: A longitudinal study in the ALSPAC birth cohort.

Allergic disease and common mental disorders frequently co-occur. However, little is known about the longitudinal impact of childhood allergy on the subsequent risk of developing anxiety or depression, and the possible biological mechanisms for this. We performed longitudinal analyses of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. The baseline sample comprised n=5256 children with allergy data available at age 7yrs. We used multivariable regression to test associations between childhood allergy at age 7yrs and: a) four inflammatory markers at age 9yrs; b) depression and anxiety measures between ages 10-24yrs. Allergy measures included biological markers (total serum immunoglobulin E (tIgE), number of positive skin prick tests (SPTs)), and presence of eczema, asthma and/or food allergy (mother reported). Inflammatory markers were interleukin-6 (IL-6), C-reactive protein (CRP), IL-4 and IL-13. We used structural equation modelling to test whether inflammatory markers mediated the association between tIgE and depression/anxiety. tIgE and having≥1 positive SPT at age 7 were associated with IL-6 levels at age 9 (adjusted β=0.09; 95% CI 0.06-0.13; p<0.001 and adjusted β=0.06; 95% CI 0.03-0.09; p<0.001 respectively), but not with CRP, IL-4 or IL13 levels. We found no strong evidence of an association between childhood allergy and subsequent depression/anxiety during adolescence and early adulthood. This finding was consistent across biological and mother-reported allergy measures. Biological markers of childhood allergy are associated with IL-6, a key inflammatory cytokine. However, childhood allergy may not have a large long-term effect on subsequent depression/anxiety.

Exposure to smoking and greenspace are associated with allergy medicine use - A study of wastewaterin 28 cities of China.

Allergies have become an important public health issue as their occurrence is reportedly on the rise around the world. Exposure to environmental factors is considered as trigger for allergic diseases. However, there was limited data on the importance of each factor, particularly in China. In this study, we aimed to investigate the association between occurrence of allergic diseases with exposure to multiple environmental factors via wastewater surveillance across 28 cities in China. The surveillance was conducted by measuring biomarkers of proxies of allergic diseases, i.e. antihistamines, asthma drug, and of smoking, i.e. cotinine in wastewater. Data of green space and air quality were also collected. We observed the level of antihistamine use were significantly associated with smoking, green space and pollen but not significant with air pollution. People in Northern China used more antihistamines than their compatriots in Southern China, an observation aligning with previous reporting of more allergy prevalence in the North than the South of China. Our study affirmed that in China smoking is responsible for a rise in allergy and asthma in the population. Meanwhile, selected sensitizing pollens (occurring during summer) could have stronger impact to trigger allergies than other pollens (occurring in winter).

Histone acetylation alteration by KAT6A inhibitor WM-1119 suppresses IgE-mediated mast cell activation and allergic inflammation via reduction in AP-1 signaling.

Activation of immunoglobulin E (IgE)-associated mast cells (MCs) triggers the onset of pro-inflammatory signals associated with type I allergic diseases. Although histone acetylation changes have been associated with inflammatory diseases, the impact of lysine-acetyltransferase (KAT) inhibitors on IgE-mediated MCs function is unclear. Potential anti-allergic effects of the KAT6A inhibitor WM-1119 on IgE-mediated MCs activation and allergic inflammation were examined in this study. WM-1119 was observed to reduce IgE-mediated degranulation in rat basophilic leukemia-2H3 cells (RBLs) and murine bone marrow-derived mast cells (BMMCs), as demonstrated by reduced the release of β-hexosaminidase (β-hex)or histamine(HA) and decreased inflammatory cytokines. Additionally, WM-1119 attenuated allergic responses in IgE-induced passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) mice. No WM-1119 effects on histamine-induced hypothermia in mice were observed. Mechanically, WM-1119 reduced levels of histone H3 lysine 14 acetylation (H3K14ac) and H3K27ac, while also reducing IgE-induced MAPK or NF-κB activity. Moreover, WM-1119 reduced activator protein-1 (AP-1) activity in a manner involving inhibition of c-Fos transcription and translation together with decreased AP-1 binding of its downstream promoters. KAT6A knockdown in MCs also reduced AP-1 activity by inhibiting c-Fos expression. H3K14ac enrichment in the Fos promoter was observed, indicating that H3K14ac may regulate c-Fos expression. In conclusion, KAT6A inhibition or knockdown was shown to reduce IgE-mediated MCs activation and allergic inflammation through a mechanism involving changes in c-Fos expression and downstream AP-1 activity consequent to down-regulation of histone acetylation. KAT6A inhibition may represent a new treatment strategy for suppressing MCs in treating allergic diseases.

Innovative formaldehyde adsorption with optimized deep eutectic solvents: An experiment and multilevel computational chemistry approach.

Formaldehyde, a hazardous gas that is exposed to everyone every day, has been proven to pose an elevated risk of respiratory problems, allergies, and chronic diseases. Adsorption technologies have proven to be a straightforward and labor-saving method to reduce indoor formaldehyde levels. Currently, extensive research has been conducted utilizing Deep Eutectic Solvents (DES) as adsorbents for harmful gases, yet the adsorption and conversion mechanisms for formaldehyde remain unclear. In this study, we highlighted the adsorption and transformation mechanisms of formaldehyde with DES employing quantum chemical and molecular dynamics calculations. Initially, thermodynamic software (CosmoTherm) was employed to calculate the logarithmic activity coefficients (LAC) of formaldehyde and determine the solid-liquid equilibrium (SLE) for 416 combinations of DES. On the basis of the eutectic point and LAC of DES, potential formaldehyde adsorbents were screened. In the second step, the DES screened out has a good formaldehyde adsorption capacity through the experiment. Finally, the reactive sites, reaction pathways, van der Waals interactions, and hydrogen bonds of DES of L-cysteine/diethanolamine (CYS-DEA) and formaldehyde were studied through a theoretical approach. This study comprehensively elucidates the screening of formaldehyde adsorbents, experimental adsorption, and adsorption mechanisms. Significantly shortens the development cycle of DES as formaldehyde adsorbents.

Isobavachin attenuates FcεRI-mediated inflammatory allergic responses by regulating SHP-1-dependent Fyn/Lyn/Syk/Lck signaling

Isobavachin, isolated from Psoralea corylifolia L. exhibits therapeutic potential for osteoporosis or skin disease. Here, we evaluated the pharmacological effects of isobavachin on IgE-dependent inflammatory allergic reactions, as well as the underlying mechanisms, in bone marrow-derived mast cells and a mouse model of passive cutaneous anaphylaxis (PCA). Isobavachin reduced IgE/Ag-stimulated degranulation, eicosanoid (leukotriene C4 and prostaglandin D2) generation, and release of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin (IL)-6). Mechanistic studies revealed that isobavachin suppressed activation of Fyn, Lyn, spleen tyrosine kinase (Syk), and lymphocyte-specific-protein-kinase (Lck), receptor-proximal tyrosine kinases that initiate and play a central role in FcɛRI-mediated mast cell activation, as well as their common downstream signaling molecules including linker for activation of T cells, phospholipase Cγ1, AKT, mitogen-activated protein kinases (MAPKs), and intracellular Ca2+. Additionally, isobavachin increased phosphorylation of Src homology region 2 domain-containing phosphatase-1 (SHP-1), thereby strengthening its interaction with Syk and Lck as well as Fyn and Lyn, resulting in de-phosphorylation of these proximal tyrosine kinases. Genetic knockdown of SHP-1 reversed the inhibitory effects of isobavachin on mast cell activation, as well as the related signaling pathways, indicating that the inhibitory effects of isobavachin are mediated by negative regulation of SHP-1-dependent Fyn, Lyn, Syk and Lck. The anti-inflammatory properties of isobavachin were also examined in macrophages. Isobavachin suppressed production of lipopolysaccharide-stimulated production of pro-inflammatory cytokines and nitric oxide. Furthermore, oral administration of isobavachin attenuated mast cell-mediated PCA reactions in mice. These results suggest that isobavachin is a potential treatment for mast cell-mediated allergic inflammatory diseases.

Injection of Lidocaine With Epinephrine for Bee Sting Large Local Reactions

Injection of Lidocaine With Epinephrine for Bee Sting Large Local Reactions

ADP101 multifood oral immunotherapy for food-allergic patients: Harmony phase 1/2 randomized clinical trial.

Oral immunotherapy is an established approach to desensitize the immune system in the context of allergic disease; however, the only currently approved product is for peanut allergy. ADP101 is a novel, pharmaceutical-grade, multifood oral immunotherapy in development to simultaneously treat single or multiple food allergies, containing allergenic proteins from 15 foods in equal parts by protein weight. The phase 1/2 Harmony trial (NCT04856865) evaluated efficacy and safety of ADP101 in participants with qualifying allergy to 1 to 5 foods in ADP101, defined as dose-limiting symptoms with a ≤100 mg challenge dose during double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomized to low-dose (1500 mg/d; 100 mg protein per food) or high-dose (4500 mg/d; 300 mg protein per food) ADP101, or matched placebo, with dose escalation followed by daily maintenance dosing over 40 weeks. The primary endpoint was the proportion of participants tolerating a ≥600 mg challenge dose of a single qualifying food without dose-limiting symptoms at the Week 40 Exit DBPCFC (ie, responders). In the primary analysis population (61 pediatric participants aged 4-17 years), a greater response rate was observed in both the high-dose ADP101 (55.0%) and low-dose ADP101 (38.1%) groups compared with pooled placebo (20.0%) (nominal P= .048, P= .306, respectively; adjusted for multiple comparisons, P= .097, P= .306, respectively). Desensitization to ≥2 foods was observed in individuals with multiple food allergies, as was desensitization at levels over 600 mg. ADP101-treated participants showed an overall reduction in skin-prick test reactivity, with an increase in maximum tolerated dose across the majority of foods tested. Adverse events were mostly mild or moderate, with no life-threatening events or deaths. The study did not meet its primary endpoint, but ADP101 demonstrated a favorable safety profile and increased the reactive threshold in DBPCFC in pediatric participants with single or multiple food allergies across multiple endpoints, warranting further clinical investigation.

Progressively differentiated TFH13 cells are stabilized by JunB to mediate allergen germinal center responses.

Allergic diseases are common and affect a large proportion of the population. Interleukin-13 (IL-13)-expressing follicular helper T (TFH13) cells are a newly identified population of TFH cells that have been associated with high-affinity IgE responses. However, the origins, developmental signals, transcriptional programming and precise functions of TFH13 cells are unknown. Here, we examined the developmental signals for TFH13 cells and found a direct and progressive differentiation pathway marked by the production of IL-21. These two pathways differed in kinetics and extrinsic requirements. However, both pathways converged, forming transcriptionally similar TFH13 cells that express the transcription factor JunB as a critical stabilizing factor. Using an intersectional genetics-based TFH13-diphtheria toxin receptor model to perturb these cells, we found that TFH13 cells were essential to drive broad germinal center responses and allergen-specific IgG and IgE. Moreover, we found that IL-21 is a broad positive regulator of allergen germinal center B cells and synergizes with IL-13 produced by TFH13 cells to amplify allergic responses. Thus, TFH13 cells orchestrate multiple features of allergic inflammation.

Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation.

Itch is a dominant symptom in dermatitis, and scratching promotes cutaneous inflammation, thereby worsening disease. However, the mechanisms through which scratching exacerbates inflammation and whether scratching provides benefit to the host are largely unknown. We found that scratching was required for skin inflammation in mouse models dependent on FcεRI-mediated mast cell activation. Scratching-induced inflammation required pain-sensing nociceptors, the neuropeptide substance P, and the mast cell receptor MrgprB2. Scratching also increased cutaneous inflammation and augmented host defense to superficial Staphylococcus aureus infection. Thus, through the activation of nociceptor-driven neuroinflammation, scratching both exacerbated allergic skin disease and provided protection from S. aureus, reconciling the seemingly paradoxical role of scratching as a pathological process and evolutionary adaptation.

Global, regional, and national epidemiology of allergic diseases in children from 1990 to 2021: findings from the Global Burden of Disease Study 2021

BackgroundAsthma and atopic dermatitis (AD) represent significant global health challenges in children. This study aimed to investigate trends in incidence, prevalence, and disability-adjusted life years (DALYs) for childhood asthma and AD from 1990 to 2021.MethodsThe study utilized information from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study 2021. The sample size for this study consisted of children with asthma or AD between the ages of 0 and 14. From 1990–2021, we calculated asthma and AD’s age-standardized incidence, prevalence, and DALYs by area, age, sex, and socio-demographic index.ResultsIn 2021, global childhood asthma prevalence reached 95.7 million cases (age-standardized rate: 4,758 per 100,000), with the Low SDI region recording 25.4 million cases. For AD, global prevalence was 72.4 million cases (age-standardized rate: 3,600 per 100,000), predominantly in Middle SDI regions (19.7 million cases). Between 1990 and 2021, age-standardized incidence rates decreased for both conditions. Geographic variations were notable: High-income North America showed the highest asthma incidence, while Western Europe led in AD prevalence. The global burden of asthma-related DALYs declined from 6.9 million in 1990 to 4.6 million in 2021, with significant regional disparities.ConclusionsDespite decreasing age-standardized rates, childhood asthma and AD continue to pose substantial health burdens globally, with marked variations across regions and socioeconomic strata. These findings emphasize the need for targeted, region-specific interventions.

Self-reported prevalence and risk factors associated with keratoconus among the adult population of Trinidad and Tobago: a cross-sectional study.

To determine the prevalence of keratoconus and its associated risk factors within the adult population of Trinidad and Tobago. A population-based cross-sectional study was conducted among adults in Trinidad and Tobago, utilizing the Keratoconus Risk Assessment Questionnaire (KRIS) for data collection. Data were exported to the Statistical Package for Social Sciences (SPSS) version 27 for analysis. Descriptive statistics were employed to summarize the variables, while logistic regression was used to identify associated risk factors, with a significance level set at p < 0.05. A total of 413 participants were included in the study, yielding a response rate of 97.4% (413/424). The prevalence of keratoconus (KC) was 1.5% (95% CI: 0.33 - 2.67%). The condition was more prevalent among females (98.5%), individuals aged 19-30years (66.7%), and participants of mixed race (50%). Allergic or atopic diseases were identified as the most common established risk factor for KC, affecting 50.1% of all participants. Among those diagnosed with KC, eye rubbing emerged as the most common established risk factor. Family history of KC (95% CI: 1.841-48.352, p < 0.007) and the use of rigid contact lenses (95% CI: 8.696-286.051, p < 0.001) were statistically significant predictors of KC. Specifically, participants with a family history of KC were 49.8 times more likely to develop the condition (OR = 49.875), while those using rigid contact lenses were 9.4 times more likely (OR = 9.436). The prevalence of KC in Trinidad and Tobago was found to be significant. Among the identified risk factors, atopy was the most common. Additionally, a positive family history and the use of rigid contact lenses were significant predictors of KC. Early screening for keratoconus in this country is strongly recommended to facilitate prompt detection and appropriate management of the condition.

Occupational allergy and climate change.

Climate change influences working conditions in various ways, affecting employee health and safety across different sectors. Climatic factors like rising temperatures, increased UV radiation, and more frequent extreme weather events pose risks to in both indoor and outdoor workers. Allergic diseases of the respiratory tract and the skin may emerge due to climate change. This review summarizes current aspects of both direct and indirect consequences of climate change and associated exposures in diverse work environments, focusing on occupational allergies. Outdoor workers, in particular, are increasing susceptible to ubiquitous pollen allergens. Additionally, they may experience climate-related increases in allergens typically associated with specific workplaces, such as Cryptostroma corticale. Changes in production processes, along with altered workplaces exposures, can lead to new sensitizations and trigger allergies, representing indirect consequences of climate change. Furthermore, lifestyle changes aimed to promoting climate protection and sustainability (e.g. the introduction of insects as a protein source or using enzymes), may also contribute to the emergence of new allergens. The emergence of new occupational sensitization sources from novel or modified allergen exposures must be addressed within the framework of workplace safety and health, necessitating proactive measures to safeguard workers and mitigate risks.

Occupational Health Risk Assessment of Microbiological Air Quality in Buhemba Small Scale Gold Mines, Tanzania

A large part of bio-aerosols is composed of biological particles such as bacteria, fungi, viruses, pollens, and their by-products such as endotoxins, metabolites, toxins, and other microbial fragments. These micro-organisms may affect human health with a wide range of adverse health effects including respiratory infections, allergies or toxic response in some individuals, especially susceptible ones. A cross-sectional study was conducted among purposely selected mining pits of Buhemba gold mine in Mara, Tanzania. To determine the microbial count, an agar strip loaded RCS&amp;reg; Microbial Air Sampler was used. Samples were collected at different microenvironments of the mining pit at a flow rate of 100 L min&amp;ndash;1 for 5 minutes to yield a sample volume of 500 liters. Morphological characterization of both bacterial and fungal colonies was carried out followed by microscopic examination of fungal and gram-stained bacterial colonies. Regression analysis between mean bacterial and fungal spore counts with environmental factors like temperature and relative humidity was performed. The total aerobic bacteria concentration varied significantly (p value&amp;lt;0.05) between sampled pits (n=15), with the highest and lowest values of 3859 CFU/m3 and 1309 CFU/m3, respectively. However, there was no significant difference in total anaerobic bacteria concentration between sampled pits. The highest and lowest values of anaerobic bacteria were respectively 4284 CFU/m3 and 1190 CFU/m3. The highest and lowest values of total fungi concentration were 3314 CFU/m3 and 646 CFU/m3, respectively. High bacteria load that exceeds 1000&amp;thinsp;CFU/m3 as recommended by WHO was found in Buhemba gold mine.

Migrasomes derived from human umbilical cord mesenchymal stem cells: a new therapeutic agent for ovalbumin-induced asthma in mice

BackgroundAsthma is a prevalent respiratory disease, and its management remains largely unsatisfactory. Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in reducing airway inflammation in experimental allergic diseases, representing a potential alternative treatment for asthma. Migrasomes are recently identified extracellular vesicles (EVs) generated in migrating cells and facilitate intercellular communication. The objective of this study was to investigate the therapeutic effects of migrasomes obtained from MSC in a model of asthma.MethodsMigrasomes produced by human umbilical cord MSCs (hUCMSCs) were isolated by sequential centrifugation. Characterization of hUCMSC-derived migrasomes were carried out by transmission electron microscopy and western blot analysis. The therapeutic effects of migrasomes on airway inflammation in ovalbumin (OVA)-induced asthmatic mice were evaluated by hematoxylin-eosin (HE) and periodic-acid schiff (PAS) staining, and their mechanism were further testified by immunofluorescent staining, real-time PCR and flow cytometry.ResultsHere, we showed that inhibition of migrasomes’ production dramatically impaired the anti-inflammatory effects of hUCMSCs in OVA animals, as evidenced by a notable increase in both the infiltration of inflammatory cells and the number of epithelial goblet cells. We successfully isolated hUCMSC-migrasomes, which were morphologically intact and positive for the specific migrasomes markers. The administration of hUCMSC-migrasomes was observed to significantly ameliorate the symptoms of airway inflammation and mucus production in asthmatic mice. Additionally, the expression of Th2 cytokines (IL-4, IL-5 and IL-13) were found to be reduced, while the activation of dendritic cells (DCs) was inhibited. HUCMSC-migrasomes could possibly be delivered to lung region after injection, and were able to be taken in by DCs both in vivo and in vitro. Notably, in vitro, migraosmes decreased the capacity of BMDCs to stimulate OVA-specific Th2-cell responses. More importantly, we found that adoptive transfer of hUCMSC-migrasomes-treated BMDCs was sufficient to protect mice from allergic airway inflammation. In addition, we found that hUCMSC-migrasomes inhibited the receptor for advanced glycation end-products (RAGE) signal in OVA-treated BMDCs in vitro and in asthma mice lung in vivo.ConclusionOur results provided the first evidence that hUCMSC-migrasomes possess anti-inflammatory properties in OVA-induced allergic mice, which may provide a novel “MSC-cell free” therapeutic agent for the management of asthma.