Iranian journal of allergy, asthma, and immunology最新文献

europathic pain can arise from injury or illness affecting the somatosensory system. It can also be triggered by cancer or chemotherapy drugs like paclitaxel. Researchers have indicated that magnesium sulfate may help in preventing neuropathy. This study aimed to investigate the effect of magnesium sulfate on paclitaxel-induced neuropathic pain by inhibiting the Tumor Necrosis Factor (TNF) Alpha - receptor-associated factor 6 - Nuclear factor kappa-light-chain-enhancer of activated B cells (TNF-α-TRAF6-NF-κB) axis. Twenty-four male rats were divided into four groups: experiment group (E)-1, E2, E3, and the control group (Co). The experimental groups and the control group received paclitaxel at a dosage of 8 mg/kg every other day, totaling four injections over seven days. In addition, magnesium sulfate was administered daily in three doses of 300, 150, and 75 mg/kg, amounting to seven injections over the course of seven days. On the seventh day, peripheral blood samples were collected from the rats, and sera were used for the analysis of TNF-α serum levels and MicroRNA-146a-5p expression using ELISA and qRT-PCR methods, respectively. The serum levels of TNF-α increased in the E1, E2, and E3 groups compared to the control group. However, there was a gradual decrease in the E1, E2 and E3 groups. The miR-146a-5p expression declined in the E1 group and increased in the E2 and E3 groups compared to the control group. This study demonstrated that administering 300 and 150 mg of magnesium sulfate decreased TNF-α synthesis and reduced the function of the TNF-α-TRAF6-NF-κB axis during the initiation step.

The exact mechanisms underlying impaired wound healing in diabetes are not fully understood. In this study, we aimed to investigate the effect of classical and non-classical monocyte ratios along with TNF-α and TGF-β plasma levels on diabetic wound healing. Twenty-four patients with confirmed type 2 diabetes and twenty healthy controls were enrolled in this study. The peripheral blood mononuclear cells (PBMC) isolation was performed  by Ficoll-Paque density gradient centrifugation method. The frequency of different subsets of monocytes was characterized in diabetic patients and  healthy controls using flow cytometry. TNF-α and TGF-β plasma levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. We found a significant difference in the frequency of classical and non-classical monocytes in healthy controls and diabetic patients. The plasma level of TNF-α was higher in diabetic patients than in healthy controls, and its level was associated with wound grade. Moreover, the plasma level of TGF-β was lower in diabetic patients rather than healthy controls. Also, our data showed a higher percentage of non-classical monocytes as wound grade increased. In conclusion, the wound healing process is affected by diabetes via changes in non-classical and classical monocyte percentages, which may be the result of TNF-α increase and TGF-β levels decreasing in diabetic patients' plasma.

Natural killer (NK) cells are crucial components of the innate immune system and have emerged as significant players in the pathogenesis of heart diseases. This review discusses recent findings regarding the multifaceted roles of NK cells in various cardiac conditions, including coronary artery disease, myocardial infarction, heart failure, myocarditis, and heart transplantation. It outlines the NK cell subsets, particularly CD56-bright and CD56-dim variations, their functional characteristics, cytokine profiles, and the inflammatory pathways they are involved. The review discusses both the beneficial and detrimental effects of NK cell activity on cardiac pathology by underlining their participation in immune regulation, tissue repair, and graft rejection dynamics. Additionally, we have addressed the impact of NK-cell-oriented environmental signals and discussed potential therapeutic approaches, such as immunomodulatory and anti-inflammatory strategies targeting NK cells. This review was therefore geared towards integrating available studies in understanding NK cell dynamics in heart disease and offering insights for future clinical interventions.

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.

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).

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.

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.

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. 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.

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.

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.