Dan Wang

Background: Anaphylaxis is a severe, fast-onset hypersensitivity reaction. Studies have shown that neutrophils play an important role in the acute phase of anaphylaxis. Activated neutrophils can release neutrophil extracellular traps (NETs); however, the potential involvement of NET-associated responses in anaphylaxis and their relationship with coagulation abnormalities remain unclear. Objective: The aim of this study was to investigate the potential involvement of NET-associated responses in anaphylaxis and their association with tissue factor (TF) expression and coagulation abnormalities. Methods: NET-associated markers, inflammatory mediators, coagulation-related parameters, and indices of anaphylactic responses were assessed in patients with anaphylaxis, passive systemic anaphylaxis (PSA) and passive cutaneous anaphylaxis (PCA) mouse models, and IgE-stimulated primary neutrophils. DNase I was used to degrade extracellular DNA structures, and tissue factor pathway inhibitor (TFPI) was used to modulate TF-related coagulation signaling. Heparin sodium and dexamethasone (DXM) were administered to evaluate whether anticoagulant or anti-inflammatory treatment was accompanied by changes in NET-associated and coagulation-related markers. Results: Bioinformatics analysis identified NET-associated genes and related biological pathways in anaphylaxis. Increased NET-associated markers were detected in patients with anaphylaxis, PSA mice, and IgE-treated primary neutrophils. DNase I treatment reduced NET-associated markers, inflammatory cytokine levels, and the experimental anaphylactic responses. Mast-cell degranulation and NET-associated extracellular DNA signals were increased in PCA mice. Elevated TF levels were detected in patients with anaphylaxis, and increased TF expression was observed in neutrophils from PSA mice. TFPI treatment was associated with reduced TF expression, inflammatory cytokine expression, and NET-associated markers in experimental models. Among 323 patients, higher D-dimer and fibrin degradation product levels were associated with greater anaphylaxis severity, and D-dimer levels were positively correlated with neutrophil counts. DNase I and TFPI treatment reduced D-dimer and fibrin degradation product levels in PSA mice. Heparin sodium and DXM attenuated experimental anaphylactic responses and were accompanied by reductions in NET-associated, TF-related, and coagulation markers. Conclusions: NET-associated markers were increased in anaphylaxis and were associated with TF expression, coagulation abnormalities, and disease severity. Extracellular DNA degradation and TF pathway modulation were associated with attenuation of experimental anaphylactic responses. These findings support a potential association among NET-associated responses, TF expression and coagulation abnormalities, and anaphylaxis, although further mechanistic studies are required to establish direct causality.

Background: Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals. Methods: The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n=178) or OB with AN (OB_AN, n=141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG. Results: OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels (PP<0.01). Conclusion: The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.

Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.

Introduction: The effect of the COVID-19 pandemic on allergic diseases is not certain, as people’s living habits and the environment have been affected by the pandemic. The present study described the influence of the COVID-19 pandemic on the allergen sensitization rate in patients with allergic diseases in central China. The results provide reliable epidemiological data for the prevention and control of allergic diseases during the COVID-19 epidemic. Methods: Data were collected from a total of 6,915 patients with symptoms of allergic diseases who visited the Third Xiangya Hospital of Central South University in China for allergen testing from January 1, 2018, to December 31, 2021. Patients were divided into a children group (60 years old). Immunoblotting was used to detect 20 serum allergen-specific IgE (sIgE) antibodies in patient serum samples. We compared the positive rates of various allergens in different age and sex groups before and during the COVID-19 epidemic, and the prevalence data of sIgE sensitization were analysed. Results: Among the 6,915 patients with symptoms of allergic diseases, 2,838 (41.04%) patients were positive for at least one of the allergens. The top three positive rates of inhaled allergens were Dermatophagoides farinae (1,764 cases, 25.51%), Dermatophagoides pteronyssinus (1,616 cases, 23.37%), and house dust (645 cases, 9.33%). The top three positive rates of food allergens were eggs (686 cases, 9.92%), milk (509 cases, 7.36%), and crabs (192 cases, 2.78%). The total positive rate of allergens was higher in men (46.99%) than in women (37.30%). Compared to 2 years before the COVID-19 epidemic, the rate of sensitization to indoor inhalant allergens increased, but outdoor inhalant allergens showed no significant change. The positive rates of milk and eggs peaked during the outbreak of COVID-19 (2020) then declined in 2021. The total positive rate of allergens was higher in males than females before and during the COVID-19 epidemic, but more allergens were different between males and females during the pandemic. Compared to middle-aged and older adults, the children and youth groups were more susceptible to allergic diseases, and they exhibited an increasing positive rate for most common allergens, especially indoor inhalant allergens, during the COVID-19 epidemic than before the pandemic. Conclusion: D. pteronyssinus and D. farinae are the most common allergens in South China. Under the background of normalization of epidemic prevention, indoor inhaled allergens should be first in the prevention and control of allergic diseases, and a combination of various indoor cleaning measures should be used to improve the efficiency of interventions.

Autoimmune diseases and autoinflammatory diseases are two types of the immune system disorders. Pyroptosis, a highly inflammatory cell death, plays an important role in diseases of immune system. The gasdermins belong to a pore-forming protein gene family which are mainly expressed in immune cells, gastrointestinal tract, and skin. Gasdermins are regarded as an executor of pyroptosis and have been shown to possess various cellular functions and pathological effects such as pro-inflammatory, immune activation, mediation of tumor, etc. Except for infectious diseases, the vital role of gasdermins in autoimmune diseases, autoinflammatory diseases, and immune-related neoplastic diseases has been proved recently. Therefore, gasdermins have been served as a potential therapeutic target for immune disordered diseases. The review summarizes the basic molecular structure and biological function of gasdermins, mainly discusses their role in autoimmune and autoinflammatory diseases, and highlights the recent research on gasdermin family inhibitors so as to provide potential therapeutic prospects.

Alopecia areata (AA) is a multi‐factors disease characterized by non‐scarring hair loss. AA could be classified into three main clinical phenotypes including patchy type AA (AAP), alopecia totalis (AT) and alopecia universalis (AU) based on the severity and areas of hair loss. Recent studies suggested immunological factor was critical in AA, but the precise aetiology and pathogenesis of AA still need exploration. In the work, we screened two gene expression profiles (GSE45512 and GSE68801) from Gene Expression Omnibus (GEO). Based on the two data sets, 10 upregulated genes and 107 downregulated genes in AA skin biopsies were identified. CCL13, as one of the remarkably upregulated genes, was found to have potential biological functions in aberrant immune response of AA according to the GO and KEGG analyses. The PPI network showed CCL13 was associated with multiple immune‐related genes. The expression of CCL13 was increased depending on the severity of disease in AA patients. Cytotoxic lymphocytes, T cells and myeloid dendritic cells accumulated remarkably in scalp tissue depending on the severity of AA, and CCL13 was significantly correlated to cytotoxic lymphocytes, T cells and myeloid dendritic cells in AA patients. Our RT‐PCR and ELISA results found CCL13 was upregulated in skin biopsy and serum of AA patients, and the immunohistochemistry (IHC) detection showed CCL13 was expressed by both the hair follicle epithelium and infiltrating immune cells. In conclusion, the upregulated of CCL13 and subsequent immune cell infiltration was related to AA, which could be a promising target for diagnosis and therapy in AA patients.