Expression of STAT3, IL-27p28, and IL-12p35 Is Deregulated and Linked to Autoimmune Markers in Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common inflammatory disorder characterized by wheals, angioedema, or both, for more than 6 weeks. Autoimmunity is held to be one of the most frequent causes, but little is known about the expression and relevance of autoimmunity-driving genes in CSU, such as STAT3, STAT1, IL-27p28, and IL-12p35. OBJECTIVE: To investigate CSU patients or the expression of STAT3, STAT1, IL-27p28, and IL-12p35 and possible links to clinical features. METHODS: Gene expression levels, in 26 CSU patients and 19 healthy controls (HCs), were determined by quantitative real-time PCR. CSU patients were assessed for total IgE and IgG-anti-TPO, markers of autoimmune CSU. RESULTS: Patients with CSU showed significantly higher expression of STAT3, but not STAT1, and 17 and 10 of 26 CSU patients had elevated STAT3 expression and STAT3/STAT1 ratios, respectively, as compared to only 1 of 19 HCs. High STAT3 expression and STAT3/STAT1 ratios were linked to low IgE and elevated IgG-anti-TPO. As compared to HCs, CSU patients had markedly lower and correlated IL-27p28 and IL-12p35 mRNA expression levels. Low IL-27p28 and IL-12p35 expression levels were linked to higher STAT3/STAT1 ratios and low IgE. CONCLUSION: STAT3 upregulation, higher STAT3/STAT1 ratios, and IL-27p28 and IL-12p35 downregulation cluster with features of autoimmune CSU. The role of STAT3 as a potential pathogenic driver of autoimmune CSU and target of treatment should be explored further.

Stimulating effect of nanocurcumin and crocin on proliferation and pluripotency of bone marrow-derived mesenchymal stem cells.

Objectives: Enhancement of proliferation, pluripotency, and self-renewal capacity as the unique features of MSCs can improve their therapeutic potential to regenerate tissues. In this context, crocin and curcumin, carotenoid compounds with outstanding medicinal properties, could be promising for cell protection and growth. This study aimed to evaluate the impact of nanocurcumin and crocin on BM-MSCs proliferation and pluripotency in vitro. Materials and Methods: BM-MSC were isolated from the iliac crest of SCI patients who were candidates for stem cell therapy. The effect of crocin and nanocurcumin on MSC proliferation was evaluated using MTT and PDT assay. The percentage of apoptotic MSCs was measured by flow cytometry. Furthermore, mRNA and protein expression of OCT4 and SOX2 as the proliferation and self-renewal related genes were quantified by real-time PCR and western blotting, respectively. Results: Our findings demonstrated that only low concentrations of nanocurcumin (0.3 and 0.7 µM) and crocin (2.5 5 µM) significantly affected MSCs proliferation and protected them from apoptosis. Also, crocin and nanocurcumin at low doses caused an elevation in the mRNA and protein expression levels of OCT4 and SOX2 genes. In contrast, high concentrations decreased the survival of MSCs and led to increased apoptosis compared with the untreated group. Conclusion: Our results suggest that using nanocurcumin and crocin separately in culturing MSCs can be considered proliferative agents to prepare the more advantageous tool for cell therapies. However, more in vitro and preclinical research is needed in this area.

A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

BACKGROUND: This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. OBJECTIVE: We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. METHODS: The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. RESULT: Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. CONCLUSION: The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Investigation of IL-6 serum level in COVID-19 patients with positive COVID-19 IgG/IgM antibody titers to check inflammation and disease progression.

OBJECTIVE: The SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), leads to severe pathogenicity and high mortality among different communities around the world. Therefore, it is important to understand the mechanisms of virus pathogenesis and the immune system's response to prevent the further spread of this virus. This study was aimed to evaluate the relationship between the serum level of interleukin 6 and positive IgG and IgM antibody levels in patients with COVID-19 to investigate inflammation and disease progression. METHODS & MATERIALS: In this study, 10 ml of EDTA blood samples were taken from 414 COVID-19 patients. Then, the plasma was separated and the levels of IgM and IgG antibodies and interleukin 6 cytokine were evaluated by ELISA and chemiluminescence methods, respectively. All data were analyzed by SPSS 22 and GraphPad prism 9 software at the significance level of P < 0.05. RESULTS: The results of this study showed that there was no significant difference in the expression of IgM and IgG antibodies between men and women. Also, a significant increase in the mean expression of IL-6 was observed only in the high concentration range (100-〉1000 pg/ml) in men compared to women (P < 0.001). In addition, in the female population, all three concentration ranges (negative, medium, and high) of IL-6 have the highest correlation with high titers (>10 U/ml) of IgM and IgG antibodies. While, in men, all three concentration ranges of IL-6 had the highest correlation with > 10 U/ml IgM antibody titers, but in the case of IgG, the highest correlation between different concentrations of IL-6 was observed with the negative or moderate titers of this antibody and there was an inverse relationship with the high titers of IgG (>10 U/ml). CONCLUSION: As a result, the relationship between different serum levels of cytokine IL-6 with different titers of IgM and IgG antibodies was observed in both male and female populations. In general, it can be concluded that the correlation between different concentrations of IL-6 with different IgM titers was similar in both men and women, but in the case of different IgG titers, this correlation was higher in women than men.

Therapeutic potential of mesenchymal stem cell-derived exosomes for allergic airway inflammation.

Due to their immunomodulatory capacities, mesenchymal stem cells (MSCs) have been extensively used as therapeutic approaches in cell-based therapy for various inflammatory diseases. Several lines of studies have shown that the most beneficial effects of MSCs are associated with MSC-derived exosomes. Exosomes are nanoscale extracellular vesicles that contain important biomolecules such as RNA, microRNAs (miRNAs), DNA, growth factors, enzymes, chemokines, and cytokines that regulate immune cell functions and parenchymal cell survival. Recently, exosomes, especially MSC-derived exosomes, have been shown to have protective effects in allergic airway inflammation. This review focused on the immune-regulatory potential of MSC-derived exosomes as nanoscale delivery systems in the treatment of allergic airway inflammation.