Sulfur dioxide inhibits mast cell degranulation by sulphenylation of galectin-9 at cysteine 74.

Objectives: Mast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO2) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO2 controlled MC degranulation. Methods: HMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO2 content was detected by in situ fluorescent probe. MC degranulation represented by the release rate of MC ß-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO2. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO2 on mast cell activation in vivo. Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO2 and support the significance of SO2/Gal-9 signal axis in the regulation of MC degranulation. Results: Degranulation was increased in AAT1-knockdowned MCs, and SO2 supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO2 contributed to IgE-mediated degranulation in vitro. Besides, SO2 inhibited IgE-mediated and hypoxia-driven MC degranulation in vivo. Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO2 sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions. Conclusion: These findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases.

Butyrate promotes visceral hypersensitivity in IBS model via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.

Emerging evidence indicates that gut dysbiosis is involved in the pathogenesis of visceral hypersensitivity (VH). However, how gut microbiota contributes to the development of VH is unknown. Here, we sought to examine the signal transduction pathways from gut to dorsal root ganglion (DRG) responsible for this. Therefore, abdominal withdrawal reflex (AWR) scores, fecal output, fecal water content, and total gastrointestinal transit time (TGITT) were assessed in Con rats, VH rats, rats treated with NaB, and VH rats treated with VSL#3. Fecal microbiota and its metabolite (short-chain fatty acids, SCFAs), mast cell degranulation in colon, lincRNA-01028, miR-143, and protease kinase C (PKC) and TRPV1 expression in DRGs were further detected. VH rats showed an increased fecal water content, a shortened TGITT, an increased abundance of Clostridium sensu stricto 1 and increased butyrate in fecal samples, an increased mast cell degranulation, an increased expression of lincRNA-01028, PKC, and TRPV1, and a decreased expression of miR-143 in DRGs compared with control rats, which could be restored by the application of probiotic VSL#3. The above-mentioned detection in rats treated with butyrate was similar to that of VH rats. We further confirm whether butyrate sensitized DRG neurons by a lincRNA-01028, miR-143, and PKC-dependent mechanism via mast cell in vitro. In co-cultures, MCs treated with butyrate elicited a higher TRPV1 current, a higher expression of lincRNA-01028, PKC, and a lower expression of miR-143 in DRG neurons, which could be inhibited by a lincRNA-01028 inhibitor. These findings indicate that butyrate promotes visceral hypersensitivity via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.IMPORTANCEIrritable bowel syndrome (IBS), characterized by visceral hypersensitivity, is a common gastrointestinal dysfunction syndrome. Although the gut microbiota plays a role in the pathogenesis and treatment of irritable bowel syndrome (IBS), the possible underlying mechanisms are unclear. Therefore, it is of critical importance to determine the signal transduction pathways from gut to DRG responsible for this in vitro and in vivo assay. This study demonstrated that butyrate sensitized TRPV1 in DRG neurons via mast cells in vivo and in vitro by a lincRNA-01028, miR-143, and PKC-dependent mechanism. VH rats similarly showed an increased abundance of Clostridium sensu stricto 1, an increased fecal butyrate, an increased mast cell degranulation, and increased expression of TRPV1 compared with control rats, which could be restored by the application of VSL#3. In conclusion, butyrate produced by the altered intestinal microbiota is associated with increased VH.

Successful treatment of a Morbihan's disease patient after a therapeutic challenge: A case report and comprehensive literature review.

Morbihan's disease is a rare condition characterized by chronic facial edema. While its exact cause is unknown, it is thought to involve local cutaneous vascularization and lymphatic drainage imbalance. Traditional treatment options are often ineffective, and no established efficient treatment exists. We present a case study of a 17-year-old male with Morbihan's syndrome who showed resistance to traditional treatments but responded well to a combination of cromolyn sodium nasal spray and oral montelukast after histopathology revealed hyperplasia of plasma cells and mast cells. This combination has not been used before for Morbihan's syndrome. Our review of the literature also provides insight for clinicians seeking to manage this condition.

Treatment of patients with evidence of mast cell-mediated itch in the absence of hives with omalizumab.

PURPOSE: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives. MATERIALS AND METHODS: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed. RESULTS: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16]. CONCLUSIONS: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.

Mast cell activation syndrome: An up-to-date review of literature.

Mast cells are a subtype of white blood cells and are involved in the immune system. These cells contain many chemical substances called mediators, which are involved in the allergic response. The fact that mast cells play a role in many events that require urgent intervention, especially anaphylaxis, has led to a more detailed study of these cells. The diseases also caused by dysfunctions of mast cells have been examined in many circumstances. For instance, mast cell activation syndrome is known as an augmented number of cells due to decreased cell death, resulting in clinical symptoms affecting many systems. The main common symptoms include flushing, hypotension, urticaria, angioedema, headache, vomiting and diarrhea. Although the underlying mechanism is not yet clearly known, we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.

RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis.

Mast cells are hematopoietic-derived immune cells that possess numerous cytoplasmic granules containing immune mediators such as cytokines and histamine. Antigen stimulation triggers mast cell granule exocytosis, releasing granule contents in a process known as degranulation. We have shown that Rho GTPase signaling is an essential component of granule exocytosis, however the proteins that regulate Rho GTPases during this process are not well-defined. Here we examined the role of Rho guanine-nucleotide dissociation inhibitors (RhoGDIs) in regulating Rho GTPase signaling using RBL-2H3 cells as a mast cell model. We found that RBL-2H3 cells express two RhoGDI isoforms which are primarily localized to the cytosol. Knockdown of RhoGDI1 and RhoGDI2 greatly reduced the levels of all Rho GTPases tested: RhoA, RhoG, Rac1, Rac2 and Cdc42. The reduction in Rho GTPase levels was accompanied by an increase in their membrane-localized fraction and an elevation in the levels of active Rho GTPases. All RhoGDI knockdown strains had altered resting cell morphology, although each strain was activation competent when stimulated. Live cell imaging revealed that the RhoGDI1/2 double knockdown strain maintained its activated state for prolonged periods of time compared to the other strains. Only the RhoGDI1/2 double knockdown strain showed a significant increase in granule exocytosis. Conversely, RhoGDI overexpression in RBL-2H3 cells did not noticeably affect Rho GTPases or degranulation. Based on these results, RhoGDIs act as negative regulators of Rho GTPases during mast cell degranulation, and inhibit exocytosis by sequestering Rho GTPases in the cytosol.

Anaphylaxis in practice: A guide to the 2023 Practice Parameter Update.

This review will summarize new research developments and clinical practice recommendations for the diagnosis and management of anaphylaxis presented in the Joint Task Force on Practice Parameters' 2023 Anaphylaxis Practice Parameter Update. It is intended to serve as a high-level summary of the 2023 practice parameter, which makes clinically impactful recommendations based on new evidence that has emerged since the 2015 practice parameter. We invite clinicians to explore the full 2023 practice parameter to better understand the research methods and underlying evidence that have informed the recommendations summarized here. There are new and evolving diagnostic criteria for anaphylaxis, rules for defining elevated tryptase levels, and recognition of signs and symptoms particular to infants and toddlers. The administration of epinephrine should not be used as a surrogate to diagnose anaphylaxis. Risk factors for anaphylaxis should be assessed on a case-by-case basis. Patient counseling and shared decision making (SDM) are essential for supporting patients' treatment decisions and capacity to manage the risk of anaphylaxis at home and in other community settings. Activation of emergency medical services following home epinephrine administration may not be required in all cases, and patients should be engaged in SDM to determine when home management may be appropriate.

Chronic skin damage induces small intestinal damage via IL-13-induced apoptosis.

The gut-skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage on mouse intestines. Following the chronic skin damage (CSD) model, 4 % sodium dodecyl sulfate (SDS) was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated (FITC)-dextran. The role of IL-13 in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, nor ILC-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut.

Prazosin Potentiates Mast Cell-Stabilizing Property of Adrenaline.

BACKGROUND/AIMS: Adrenaline quickly inhibits the release of histamine from mast cells. Besides ß2-adrenergic receptors, several in vitro studies also indicate the involvement of α-adrenergic receptors in the process of exocytosis. Since exocytosis in mast cells can be detected electrophysiologically by the changes in the membrane capacitance (Cm), its continuous monitoring in the presence of drugs would determine their mast cell-stabilizing properties. METHODS: Employing the whole-cell patch-clamp technique in rat peritoneal mast cells, we examined the effects of adrenaline on the degranulation of mast cells and the increase in the Cm during exocytosis. We also examined the degranulation of mast cells in the presence or absence of α-adrenergic receptor agonists or antagonists. RESULTS: Adrenaline dose-dependently suppressed the GTP-γ-S-induced increase in the Cm and inhibited the degranulation from mast cells, which was almost completely erased in the presence of butoxamine, a ß2-adrenergic receptor antagonist. Among α-adrenergic receptor agonists or antagonists, high dose prazosin, a selective α1-adrenergic receptor antagonist, significantly reduced the ratio of degranulating mast cells and suppressed the increase in the Cm. Additionally, prazosin augmented the inhibitory effects of adrenaline on the degranulation of mast cells. CONCLUSION: This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell-stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by ß2-adrenergic receptors.

Beyond Midostaurin: Role of Avapritinib in Managing Systemic Mastocytosis.

We present a case of an adult male who presented with pancytopenia accompanied by symptomatic anemia, necessitating chronic transfusions. He was diagnosed with systemic mastocytosis with an associated hematologic neoplasm. Following an inadequate response to midostaurin therapy, the patient was initiated on the newly approved avapritinib. The patient showed significant improvements in all three blood cell lines; however, he developed leg edema, blepharedema, and gum bleeding on this medication. This case underscores the intricacies of managing a patient with advanced systemic mastocytosis, the emerging role of highly selective KIT inhibition in its treatment, and the practical management of adverse medication effects.

Biomarkers of peanut allergy in children over time.

BACKGROUND: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort. METHODS: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7-12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7-12 years. PA status was determined at the 7-12 year time point. RESULTS: The prevalence of PA was 2.1% at 7-12 years. Between 3 and 7-12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut-sIgE from 36 months to 7-12 years, but MAT remained low. PS children had low biomarkers across time. CONCLUSIONS: In this cohort, few children outgrow or develop new PA between 36 months and 7-12 years. Children with persistent PA have raised SPT, peanut-sIgE, Ara h 2-sIgE and MAT evident from infancy that consistently increase over time.

Imatinib and Trigger Avoidance for Mast Cell Activation Syndrome Presenting With Attacks of Abdominal Pain, Nausea, Vomiting, and Diarrhea.

The etiology for concurrent attacks of abdominal pain, nausea, vomiting, and diarrhea can be obscure. Mast cell activation syndrome is not usually considered in this differential diagnosis. A 53-year-old paint salesman suffered severe attacks of these symptoms for the 3 decades of his career. Nortriptyline, loperamide, hyoscyamine, and ondansetron failed to address his symptoms. Mast cell activation syndrome was ultimately diagnosed. Intravenous mast cell-targeted therapy reduced severity of attacks. Multiple oral mast cell-targeted treatments were ineffective, but addition of low-dose imatinib resulted in dramatic improvement. Recognition that paint-fume exposure-triggered attacks led to behavioral modifications which further reduced symptoms.

Breast Implant Illness May Be Rooted in Mast Cell Activation: A Case-Controlled Retrospective Analysis.

Objective: To investigate the possible association between breast implant illness (BII) and mast cell activation syndrome (MCAS), which often manifests increased mast cells (MCs) in assorted tissues and may explain BII symptoms. Background: Mechanisms by which implants cause BII symptoms remain unclear, but BII and MCAS symptom profiles heavily overlap, warranting investigation of potential linkage. Methods: We retrospectively analyzed 20 implant patients who underwent explantation and total capsulectomy; 15 self-reported preoperatively they had BII (subject group); 5 felt they did not [control group 1 (CG1)]. Five prophylactic mastectomy patients constituted control group 2 (CG2). Subjects and CG1 patients completed BII symptom questionnaires preoperatively and multiple points postoperatively. With CD117 staining, average and maximum mast cell counts (MCCs) in resected tissues were determined. Results: Mean BII symptom score 2 weeks postexplantation was reduced by 77% (P < 0.0001), and 85% by 9 months. Analysis suggested BII in CG1 patients, too, who improved similarly. Among CG2 patients, healthy breast tissue showed mean and maximum MCCs of 5.0/hpf and 6.9/hpf. Mean and maximum MCCs in capsules in BII patients were 11.7/hpf and 16.3/hpf, and 7.6/hpf and 13.3/hpf in CG1 patients. All intergroup comparisons were significantly different (P < 0.0001). Conclusions: MCCs in peri-implant capsules in BII patients are increased; some implanted patients appear to have unrecognized BII. Given that neoantigenic/xenobiotic exposures commonly trigger dysfunctional MCs in MCAS to heighten aberrant mediator expression driving inflammatory and other issues, further investigation of whether BII represents an implant-driven escalation of preexisting MCAS and whether an MCAS diagnosis flags risk for BII seems warranted.

Inhibition of pseudo-allergic reactions by vitamin K3 directly targeting GAB1 in mast cells.

BACKGROUND: Vitamin K3 (VK3), a fat-soluble synthetic analog of the vitamin K family, has coagulant, anti-inflammatory, antibacterial, and anticancer properties. Pseudo allergy is a IgE-independent immune response associated with mast cells. This study investigated the role of VK3 in IgE-independent mast cell activation. METHODS: Substance P (SP) was used to induce LAD2-cell activation in order to analyze the effects of VK3 in vitro. Cutaneous allergy and systemic allergy mouse models were used to analyze the anti-pseudo-allergic effects of VK3. Proteome microarray assays were used to analyze VK3-binding protein. Biolayer interferometry and immunoprecipitation were used to verify interaction between VK3 and its key targets. RNA interference was used to determine the role of GAB1 in LAD2cell activation. RESULTS: VK3 inhibited SP-induced LAD2-cell activation, and resulted in the release of ß-hexosaminidase, histamine and cytokines; VK3 inhibited SP-induced pseudo allergic reactions in mice, and serum histamine and TNF-α levels decreased. Degranulation of skin mast cells was reduced; GAB1 in mast cells was stably bound to VK3. GAB1 participated in SP-induced LAD2-cell activation. GAB1 knockdown in LAD2 cells prevented SP-induced ß-hexosaminidase release, calcium mobilization and cell skeletal remodeling. VK3 directly binds to GAB1 and reduces its expression to inhibited SP-induced LAD2 cell activation. CONCLUSION: The anti-pseudo-allergic activity of VK3 was confirmed in vitro and in vivo. VK3 can inhibit SP-induced mast cell activation by directly targeting GAB1. This study provides new insights on the activity of VK3 and the mechanism of pseudoallergic reaction.

Stress Affects Mast Cell Proteases in Murine Skin in a Model of Atopic Dermatitis-like Allergic Inflammation.

Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.

Histochemical and immunohistochemical investigation of the number and localization of mast cells in the feline tongue.

This is the first study to describe the subtypes, number and distribution of mast cells (MC) in cat tongue by histochemical and immunohistochemical methods. Six male adult felines' tongue tissue samples consist of the study's material. Samples were fixed in 10% formaldehyde. MC number and distribution in the feline tongue were assessed using toluidine blue. Also, sections taken from blocks were stained in alcian blue/safranin O (AB/SO) combined dyes to determine the MC subtypes. The Streptavidin biotin complex method using anti-chymase and anti-tryptase primary antibodies was used for immunohistochemistry. Metachromatic MCs were mainly observed in the lamina propria close to the multilayered keratinized stratified squamous epithelium. The high number of MCs in this region may be because the dorsal surface of the tongue plays an essential role in the defence system of tongue tissue and, thus, of the body as a whole. Additionally, the number of MCs stained with AB (+) (1.7 ± 0.08) in the feline tongue was statistically higher than those with SO (+) (0.18 ± 0.02). This might be interpreted as an indication that MC heterogeneity may be due not only to their staining properties but also to their localization. It is also conceivable that the high histamine content may be a factor in this. Tryptase-positive MCs were found in the loose connective tissue around blood vessels, between the glands, as solitary cells, or in groups of several cells. Chymase-positive MCs were observed more individually rather than in groups. Moreover, chymase-positive MCs were detected to be located in the filiform papillae subepithelial and in the blood vessels' immediate vicinity. Animals often lick themselves to clean themselves and promote healing. For this reason, it is very important to protect the tongue, which is in direct contact with the external environment, against foreign agents. Considering both the functional and protective properties of the tongue, we concluded that MCs may play a role in oral cavity immunity and protective effect.

CircRNA_0008668 Sponges miR-1301-3p to Promote the Inflammatory Response in Allergic Rhinitis by Upregulating GATA6 Expression.

AIMS: We aim to explore GATA6 modulation in allergic rhinitis (AR). BACKGROUND: Circular RNAs (circRNAs) and microRNAs (miRNAs) are involved in inflammatory responses; GATA6 is also known to regulate multiple inflammatory pathways. However, the mechanism of regulation of AR between them is unclear. OBJECTIVE: We expect that this study will provide new treatment options for AR from a GATA6 perspective. METHODS: In vitro, AR models were employed to examine the efficacy of our study, where we utilized monoclonal anti-2,4,6-dinitrophenyl immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA) to induce rat basophilic leukemia cells (RBL-2H3 cells). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to measure the expression of circ_0008668, miR-1301-3p, GATA6, and cellular inflammatory markers. Enzyme-linked immunosorbent assay (ELISA) was used to measure concentrations of beta-hexosaminidase, histamine, and cellular inflammatory factors including TNF-α, IL-1ß, IL-4, and IL-5. In addition, western blot, RNA pull-down, and luciferase assays were performed to validate the molecular mechanism by which circ_ 0008668 and miR-1301-3p interactions promote GATA6 to ameliorate the inflammatory state of RBL-2H3 cells. RESULTS: In the in vitro model of AR, the expression levels of circ_0008668 and GATA6 were elevated, whereas that of miR-1301-3p was decreased. Pull-down assays confirmed that circ_0008668 efficiently binds miR-1301-3p and its overexpression leads to upregulation of the levels of GATA6, cellular inflammatory factors (IL-4, IL-5, TNF-α, and IL-1ß), and markers associated with inflammatory signaling pathways (NLRP3, ERK1/2, and P65 protein phosphorylation). In addition, miR-inhibitor with circRNA enhanced GATA6 and NLPR3 expression and activated inflammatory pathway activity. In particular, miR-mimic was effective in reversing the onset of this inflammatory state. CONCLUSION: Our results indicate that circ_0008668 promotes the inflammatory state of mast cells by sponging miR-1301-3p to target GATA6, which in turn affects the allergic response to AR. This process could improve the current diagnosis of AR patients and clinical treatment.

Dose-dependent protective effects of Lactobacillus rhamnosus GG against stress-induced ulcer.

BACKGROUND: Stress-related diseases are on the rise and stress is one of the common factors that lead to ulcer. Stress-induced mucosal bleeding is a serious complication observed in many critically ill patients. Due to the harmful side effects of proton pump inhibitors, natural and active alternative treatment methods for peptic ulcer treatment that are safe in terms of side effects are an urgent need for human health. We aimed to investigate the dose-dependent protective effects of Lactobacillus rhamnosus GG (LGG) against stress ulcers induced by cold restraint stress in rats. This study was performed in a total of 42 rats, in control group (C), stress group (S), pantoprazol (20 mg kg-1 day-1) group (P), LGG (3 × 108 cfu mL-1 day-1) + stress group (M1), LGG (15 × 108 mL-1 day-1) + stress group (M5) and LGG (30 × 108 mL-1 day-1) + stress group (M10) (each n = 7). Ulceration areas (mm2) were determined quantitatively with ImageJ software. Glucocorticoid, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by ELISA and malondialdehyde levels were determined by spectrophotometric measurement. Histopathological examinations were performed in gastric tissue. RESULTS: Therapeutic dose of LGG increased CAT, SOD and GPx levels; prevented excessive activation of the hypothalamic-pituitary-adrenal axis; reduced ulceration and bleeding in the gastric mucosal layer; and provided stabilization of mast cells. CONCLUSIONS: We can suggest that LGG may be beneficial for reducing the negative effects of stress on the body, for protecting against ulcer disease and for reducing or preventing the risk of stress-induced gastrointestinal bleeding in patients staying in intensive care units. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Mast Cell Activation Syndrome: current understanding and research needs.

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities which have gained increased attention from patients and medical providers. While several descriptive publications about MCAS exist, there are many gaps in knowledge resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell (MC) activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to MC activation in MCAS patients remain to be elucidated. The purpose of this manuscript is to summarize the known literature, identify gaps in knowledge, and highlight research needs. Several topics are covered: 1) Contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; 2) Mechanistic research; 3) Management of typical and refractory symptoms, and 4) MCAS-specific education for patients and healthcare providers.