Iranian Journal of Allergy, Asthma and Immunology

Investigating the Relationship between FGF2 Gene Expression and Airway Remodeling in Severe Asthma

Mahsa Manafi Varkiani — 2025-02-28

Severe asthma causes chronic airway inflammation and structural changes in the bronchial wall. Fibroblast growth factor 2 (FGF2) plays an inflammatory role in specific pathways in airway remodeling in asthma. Assessing the relationship between sputum pattern, bronchial thickness by high-resolution computed tomography (HRCT) scan, and FGF2 expression level can evaluate the role of FGF2 in asthma remodeling.

The study aimed to investigate the correlation between airway wall thickness and FGF2 gene expression in 100 participants with severe asthma. The method involved measuring airway wall thickness using HRCT and analyzing FGF2 gene expression through real-time reverse transcriptase polymerase chain reaction. The participants were divided into 2 groups based on bronchodilator responsiveness and classified into different asthma phenotypes based on sputum cell count.

The baseline data did not show a significant difference between the groups. The study found significant differences in airway variables between different asthma subgroups. FGF2 expression was associated with various characteristics of asthma, including body mass index, forced expiratory volume in 1 second (FEV1), and airway wall thickness. The receiver operating characteristic curve analysis showed that a fold change higher than 2.42 in FGF2 expression indicated asthma.

Based on our research, FGF2 may play a critical role in airway thickness regardless of inflammation. We found increased FGF2 levels with disease severity and wall thickness in atopic severe persistent asthma patients with FEV1 below 60%. Further research is needed to understand FGF2's role across broader FEV1 ranges and other phenotypes.

Effectiveness of the Nasal Irrigation Effectiveness in Treating Allergic Rhinitis in Children 6 to 12 Years Old

Bita Yadegary — 2025-02-28

Nasal irrigation, a nonpharmacological intervention for alleviating nasal symptoms, has yet to gain widespread acceptance among caregivers due to procedural ambiguities and the absence of a standardized protocol. This study aimed to evaluate the efficacy of normal saline nasal irrigation in managing allergic rhinitis among children aged 6 to 12 years.

This prospective, randomized, single-blind trial enrolled children aged 6 to 12 with allergic rhinitis. Fourthy-eight patients were randomly assigned to receive either standard care (oral antihistamine and intranasal corticosteroid) or standard care plus nasal irrigation with saline solution. Symptom severity, assessed using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) at baseline, 1, and 3 months, included rhinorrhea, nasal congestion, sneezing, pruritus, ocular symptoms, and functional impairment.

The intervention group demonstrated statistically significant improvements in several domains post-intervention. Specifically, a marked reduction in sneezing frequency and nasal cleansing requirements was observed. Moreover, this group reported significantly lower ocular symptoms, including irritation, itching, and watering, relative to the control group. Although overall PRQLQ scores did not differ significantly between groups, the intervention group exhibited lower scores at the 1- and 3-month follow-ups, indicative of enhanced quality of life. These findings suggest a potential beneficial effect of the intervention on participant well-being.

The findings of this study indicate that nasal irrigation with 0.65% saline solution 4 times daily may serve as an effective adjunct treatment for children with allergic rhinitis. This regimen was associated with significant enhancements in both nasal symptom severity and quality of life.

Neutrophil Markers as Predictors of COVID-19 Severity at Hospital Admission: A Cross-sectional Study

Maedeh Vahabi — 2025-02-28

COVID-19 is capable of undermining self-tolerance in a host's immune system and triggering autoimmunity by hyper-activating the innate and adaptive immune systems, which has not investigated in Iranian society until now. In the innate immune system neutrophils are the predominant immune cells that protect the human body against invaders.

Here, we sought to explore 2 important variables related to neutrophil: DNA complexes with myeloperoxidase (MPO-DNA) as a reliable indicator of neutrophil extracellular traps (NETs) by MPO-DNA complex evaluation using a sandwich ELISA and the underlying role of IL-8 in (NETs) formation during COVID-19 infection.

According to our results, in 103 COVID-19 patients, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in ICU patients (14.62±11.81) compared to non-ICU patients (3.16±3.33). Elevated IL-8 levels were observed in COVID-19 patients, particularly in ICU patients. MPO-DNA levels, indicating NETosis, were significantly higher in COVID-19 patients and strongly correlated with neutrophil counts (r=0.472).

Thus, our studies suggest that neutrophils count, IL-8, and MPO-DNA can be used as powerful biomarkers in diagnosing COVID-19 severity. patients with severe COVID-19 infection are prone to heart disease because most of them develop excessive NET formation. Additionally, In COVID-19 patients, a higher MPO-DNA level may increase the risk of developing heart disease too.

Upregulation of MicroRNA-144 Suppresses Nrf2 Antioxidant Signaling Pathway in Patients with Severe COVID-19

Mahdieh Nasirzadeh — 2025-02-28

MicroRNAs (miRs) play a pivotal role in the pathogenesis of viral infections. It has been proven that the Nrf2 (NFE2 like bZIP transcription factor 2) antioxidant signaling pathway is inhibited in COVID-19 patients. Two microRNAs (MIR144 and MIR153-1) have been identified as important Nrf2 regulators. The aim of this study was to analyze the MIR144 and MIR153-1 expression in COVID-19 patients and investigate their association with the Nrf2 signaling pathway.

The study had 82 participants with both mild and severe COVID-19 manifestations and 25 healthy as a control group. Ficoll density-gradient centrifugation was used to separate peripheral blood mononuclear cells from ethylenediaminetetraacetic acid blood tubes. MIR144, MIR153-1, and NFE2L2 expressions were studied using real-time polymerase chain reaction. We employed the commercially available enzyme-linked immunosorbent assay to measure plasma Nrf2 protein concentration and the activity of antioxidant enzymes, superoxide dismutase, and catalase.

Compared to the control group, MIR144 expression was significantly increased in the severe group, while NFE2L2 expression decreased. There was no significant difference in the MIR153-1 expression rate between COVID-19 patients and controls. Nrf2 protein and antioxidant enzyme activity significantly decreased in the severe group. A negative correlation between MIR144 expression and Nrf2 protein concentration was observed.

Taken together, the current study's findings showed that MIR144 upregulation probably interferes with the Nrf2 antioxidant signaling pathway in COVID-19 patients.

Effect of Remimazolam on Cellular Immune Response and Postoperative Recovery in Patients Undergoing Laparoscopic Colorectal Cancer Surgery

Jianyan Wu — 2025-02-28

We aimed to evaluate the effect of remimazolam-based general anesthesia on cellular immune function and postoperative recovery quality in patients undergoing laparoscopic radical colorectal cancer surgery.

A total of 90 patients scheduled for elective laparoscopic colorectal cancer radical surgery were randomly divided into 2 groups: the remimazolam group (Group R) and the propofol group (Group P), with 45 patients in each group. Anesthesia induction in Group R involved intravenous remimazolam, and in Group P, intravenous propofol until the loss of consciousness (modified observer’s assessment of alertness/sedation [MOAA/S] score 1–2). Both groups then received intravenous sufentanil and cisatracurium for intubation. Cellular immune function markers (CD3⁺, CD4⁺, CD8⁺ T and natural killer [NK] cells) were recorded at different time points. Quality of Recovery [QoR]-15 scale scores, hemodynamic parameters, sedation scores (Riker and Ramsay scales), recovery times and adverse events were also recorded.

Compared to Group P, Group R had significantly higher NK, CD3⁺, and CD4⁺ cell levels immediately after surgery and at 24 hours postoperatively. Group R showed a significantly lower incidence of intraoperative hypotension, bradycardia, and vasopressor use. Additionally, QoR-15 scores at 24 and 72 hours were higher in Group R. There were no significant differences in Riker or Ramsay scores, extubation time, post-anesthesia care unit stay, or the incidence of postoperative nausea, vomiting, and drowsiness between the 2 groups.

Compared with propofol, remimazolam anesthesia results in better perioperative immune function preservation, reduced intraoperative hypotension and bradycardia, and improved postoperative recovery quality in patients undergoing laparoscopic radical colorectal cancer
surgery.

Establishing an HLA-Typed Plateletpheresis Donor Registry at the Iranian Blood Transfusion Organization

Fatemeh Sabaghi — 2025-02-28

Administering human leukocyte antigen (HLA)-compatible platelets is a tactic for treating patients with poor responses to random platelet injections. HLA-matched platelet provision requires many donors with HLA-typed and organized information. This study, the first of its kind in Iran, aimed to develop a registry system of HLA-typed platelet donors to facilitate the provision of compatible platelets to patients, leveraging the diversity of HLA alleles across Iran's various provinces.

This study involved the HLA-typing of 1850 plateletpheresis donors, who were also registered as unrelated stem cell donors, across all blood centers in Iran from 2015 to 2022. HLA-A and HLA-B genotyping was conducted at a low-resolution using polymerase chain reaction-sequence specific primers (PCR-SSP) and real-time PCR. Statistical analysis was performed to determine allelic genotypes and donor profiles.

The majority of the donors were male (99.7%), with a mean age of 36 years. The high donor rate
in Tehran indicates a larger pool of potential HLA-platelet donors due to a denser population and
more donation facilities. The donors were recruited for HLA-compatible plateletpheresis. The frequency of HLA-AB alleles among donors was relatively consistent with those documented by Iranians.

Our findings can be utilized to create a foundational HLA database. A registry system for HLA-typed platelet donors is crucial due to high HLA polymorphism and ethnic diversity. This system facilitates the rapid identification of compatible donors based on HLA typing. Additional inquiries are needed to expand the plateletpheresis registry and make a request-supply mechanism between the Iranian Blood Transfusion Organization and hospitals.

Analyzing the Role of CircSnx5 in an Animal Model of Multiple Sclerosis

Leila Mohamed Khosroshahi — 2025-02-28

Circular RNAs (circRNAs) are endogenous non-coding RNA molecules that form covalently closed molecular loops. By regulating gene expression, circRNAs are known to play crucial roles in the development and progression of various diseases, including autoimmune, neoplastic, and neurological disorders.

In this study, we examined the expression of circSnx5 in inflamed CNS tissue at different stages of experimental autoimmune encephalitis (EAE), an animal model for multiple sclerosis (MS), as well as in T cells that were activated and differentiated into different T helper phenotypes (Th1, Th17, Treg). EAE was induced and spinal cord tissues were isolated at different time points following disease induction. CD4⁺ T cells were isolated from mouse splenocytes and differentiated toward Th1, Th17, and Treg phenotypes, followed by the analysis of circSnx5 expression.

Compared with control mice, enhanced expression of both circular and linear forms of Snx5 was detected in EAE lumbar spinal cords at the peak and post-peak phases of the disease. However, the ratio of the circular to linear forms (CLR) was decreased in EAE mice compared with controls. Expression of circSnx5 was highly correlated with the levels of inflammatory cytokines in the spinal cord tissue. Significant decreases were observed in circSnx5 expression levels following polyclonal activation of splenocytes. The expression of circSnx5 was also downregulated in differentiated T cells directed toward Th1, Th17, and Treg.

Our findings suggest a potential role of circSnx5 in autoimmune neuroinflammation. The altered expression of circSnx5 during activation and differentiation may offer valuable insights into potential strategies for regulating inflammation in multiple sclerosis (MS).

Inhibitory Effect of Propofol on Type II Inflammation in Mice with Allergic Rhinitis

Xi Chen — 2025-02-28

Propofol, a quick‑acting systemic anesthetic agent widely used in general anesthesia, can alleviate airway T-helper 2 (T_H2) inflammation. Group 2 innate lymphoid cells (ILC2s) are a newly discovered group of lymphoid cells and play key roles in allergic rhinitis (AR). We aimed to investigate the regulation of ILC2s treated with propofol and its possible mechanisms in a mouse model.

An ovalbumin (OVA)-sensitized and challenged mouse model was established. Nasal lavage fluid (NLF) and tissue samples were collected for the detection of inflammatory cells, type II cytokines, and ILC2s using Giemsa staining, enzyme-linked immunosorbent assay, and flow cytometry. CD4⁺ T cells and ILC2s were cocultured and detected by flow cytometry to confirm the proportion of T_H2 cells.

Compared with OVA-sensitized and challenged mice, propofol-treated model mice presented decreased type II cytokine levels and total numbers of cells, eosinophils, neutrophils, and macrophages in NLF. Mice treated with propofol presented decreased nasal ILC2 frequency. Moreover, the nasal expression of GATA binding protein 3 (GATA3) and retinoid-related orphan receptor α (RORα), as well as the levels of IL-5 and IL-13, were significantly inhibited after propofol treatment. Compared with those cultured alone, cocultures of ILC2s and CD4⁺ T cells resulted in significantly more T_H2 cells. When propofol was added, the percentage of T_H2 cells significantly decreased. This effect was alleviated when anti-major histocompatibility complex class II (anti-MHC II) protein was added.

Our study provides preliminary evidence that propofol can play an inhibitive role in AR by regulating innate and adaptive immunity.

Evaluation of Heterologous Prime-boost Vaccine Strategy Using Full-length Cytomegalovirus Glycoprotein B to Trigger BALB/c Mice Immunity

Somayeh Azadfar — 2025-02-28

Human cytomegalovirus glycoprotein B (gB) emerges as a viable candidate for eliciting neutralizing antibodies. This research specifically focused on exploring the immune reaction prompted by the nonglycosylated variant of the gB, with a comprehensive assessment of humoral immunity in mice.

The gB coding sequence was optimized and expressed in pET-15b. Additionally, pcDNA3.1(+) vectors were also used for cloning the same gB sequence as the DNA vaccine. The gB was purified using a Ni-NTA chromatographic column. SDS-PAGE and Western blotting were used to confirm protein expression and purification. Using the prime-boost strategy, 8 different BALB/c mice were injected with DNA vaccine plus gB heterologous vaccine at 3 intervals. We evaluated the interferon (IFN-γ), interleukin (IL-4), immunoglobulin (Ig) G1, IgG2a, and IgG2b using enzyme-linked immunosorbent assay.

It was shown that the mice administered with DNA vaccine plus gB had higher IFN- γ and IL-4 levels compared to controls. On the other hand, the mice that received 3 doses of gB showed the highest levels of IgG1 and IgG2a. However, IgG2b was at its highest in mice administrated with DNA vaccine plus gB. The total IgG was higher in mice that received gB than in other interventions.

According to the findings, the DNA vaccine enhanced total IgG in immunized mice more effectively than the gB. This could be attributed to conformational changes owing to a lack of glycan moiety. Furthermore, combining nonglycosylated gB with DNA as a heterologous vaccine strategy enhances innate immunity by increasing the IFN- γ levels.

Effects of c-Kit Receptor, AKT, and NF-κB Inhibitors on Immune Evasion in Multiple Myeloma Cells

Abbas Ranjbar — 2025-02-28

Up-regulation of immune checkpoint ligands and secretion of soluble factors in the tumor microenvironment led to the survival of cancerous plasma cells in the bone marrow milieu. Therefore, we investigate the relationship between the inhibition of c-Kit receptor, AKT, and NF-κB signaling pathways and the regulation of immune escape mechanisms in multiple myeloma.

The U266B1 cell line was treated with Masitinib as a c-Kit receptor inhibitor, Perifosine as AKT inhibitor, and Bortezomib as NF-κB inhibitor either in single or combined form. Apoptosis and cell viability were evaluated using flow cytometry and MTT assays, respectively. The relative expression of programmed death-ligand 1 (PD-L1), poliovirus receptor (PVR), and interleukin 6 (IL-6) were determined by real-time PCR. Also, the secretion of IL-6 was measured by ELISA.

Our findings demonstrated decreased proliferation of U266B1 cells after co-treatment with Masitinib, Perifosine, and Bortezomib. An increase in apoptosis was observed in the co-treatment of Masitinib and Perifosine. Furthermore, results elucidated that the expression of PD-L1 and IL-6 decreased after treatment with Masitinib, Perifosine, and Bortezomib in both single and co-treatments. Regarding PVR, combined treatment of U266B1 cells with Masitinib, Perifosine, and Bortezomib decreased the expression level of PVR.

We showed that c-Kit receptor, AKT, and NF-κB pathway inhibitors not only serve as cytotoxic drugs but also inhibit the immune escape mechanisms of malignant plasma cells by disrupting signaling pathways.

Ellagic Acid Ameliorates Ovarian Cancer via Modification of Pyroptosis and Inflammation

Yan Sun — 2025-02-28

Ovarian cancer is 1 of the most serious female malignancies worldwide. Despite intensive efforts to overcome ovarian cancer, there remain limited treatment options for this disease. Ellagic acid (EA), a well-known phytochemical with anti-inflammatory properties, is suggested as a therapeutical strategy as it can inhibit the growth of certain cancer cells. However, its effect on human ovarian carcinoma cells has not yet been fully elucidated. The present study aimed to explore the effect of EA on ovarian carcinoma and further expound the underlying mechanisms of EA-induced ovarian cancer cell death.

Human ovarian carcinoma cell lines, A2780 and OVCAR3, were treated with EA (0, 10, 20, 50, and 100 μM) and assessed for viability, cell cycle (cyclin D1 and cyclin E), pyroptosis (gasdermin D [GSDMD] and gasdermin E [GSDME]), autophagy (microtubule-associated protein 1A/1B-light chain 3 [MAP1LC3] and autophagy protein 5 [ATG5]), and inflammation (interleukin [IL]-1b and IL-6) via 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT), real-time polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA).

The findings showed that EA could significantly inhibit cell viability, decrease cyclin D1 and E levels, downregulate GSDMD and GSDME, and suppress the levels of inflammatory markers, including IL-1b and IL-6. However, the protein levels of autophagic markers including LC3 and ATG5 remained mostly unchanged.

The findings suggest that EA could suppress ovarian cancer cell viability and proliferation by arresting both cell lines at the G1 phase of the cell cycle through modification of cell death mediated by inflammatory-caused pyroptosis.

Rare Allergic Reaction to Local Anesthesia: A Case Report

Rakhi Issrani — 2025-03-01

One of the most commonly used local anesthetic (LA) agents in dentistry is lidocaine. Hypersensitivity reactions to lidocaine have been reported. In such cases, it is crucial to record a detailed clinical history and perform allergy testing to select a suitable alternative LA agent.

This report presents the experience of observing a case of lidocaine allergy, supported by a review of the literature on the condition. A rare case of delayed hypersensitivity reaction to lidocaine is reported, where the patient exhibited swelling and erythema of the upper labial mucosa. Intradermal testing confirmed an allergic reaction to lidocaine.

The patient was successfully treated with an alternative LA agent, allowing for the completion of dental procedures without complications. This highlights the importance of careful diagnostic measures to manage such rare but significant allergic reactions effectively.

This case highlights the importance of recording a proper clinical history and performing allergy testing before the administration of LA to prevent severe allergic reactions. Additionally, patients identified as allergic to LA agents should be thoroughly counseled, informed about their condition, and provided with a clear explanation of all available treatment options