Oral immunotherapy (OIT) is a novel approach to desensitization and tolerance induction in food allergy patients. This study aimed to design and implement a new wheat OIT protocol, evaluate its efficacy in tolerance induction, and assess specific immunoglobulin-E (IgE) and regulatory T cell changes.
From 2015 to 2017, 26 patients with confirmed IgE-mediated hypersensitivity to wheat were treated via oral immunotherapy (OIT). Patients with prior anaphylactic episodes underwent OIT using the rush method. Specific IgE concentrations and the number of regulatory T cells (CD4+ CD25+ FOXP3+ T cells) were measured using Allergy Screen immunoblot assay and flow cytometry, respectively. This study was registered in the Iranian Registry of Clinical Trials (IRCT20181220042066N1).
The results revealed success rates of 100% and 93.3% for desensitization and tolerance. Specific IgE was significantly reduced after 12 months of OIT. No significant change in regulatory T cell numbers was observed.
In view of the promising findings of this study, the proposed OIT protocol could be viewed as an effective and valuable method to induce tolerance and desensitization in wheat allergic patients.

Inflammation is an essential contributor to Coronavirus disease 2019 (COVID-19).  
In this regard, finding a prognostic indicator is valuable because the treatment will be more effective if critical patients with high inflammation are diagnosed earlier. We aimed to evaluate some hematologic markers for COVID-19 and assess their association with the severity of the disease.
A total of 154 COVID-19 patients were laboratory-confirmed and admitted to Imam Khomeini Hospital Complex, Tehran, Iran, from February 12, 2020, to April 4, 2020, and 55 healthy individuals were enrolled in the study. The severity of the patients' illnesses was classified into three subgroups according to the types of oxygen therapies (moderate (61), severe (28), and critical (43)) and examined the different ratios of total white blood cell (WBC) count, neutrophil to lymphocyte ratio (NLR), platelet to monocyte ratio (PLR), macrophage to lymphocyte ratio (MLR), derived NLR ratio (dNLR), and some biochemical tests.
COVID-19 patients had higher levels of NLR, MLR, PLR, and dNLR than healthy subjects. receiver operating characteristic (ROC) analysis of the curve revealed that NLR and dNLR had a high diagnostic value to differentiate COVID-19 patients from healthy subjects (area under the curve [AUC]=0.923 and 0.910, respectively) and predict mortality (AUC=0.726 and 0.735, respectively).
NLR and dNLR may be reliable markers to evaluate the severity of COVID-19. NLR and dNLR had a high diagnostic value for differentiating COVID-19 patients from healthy subjects, and they could predict the severity and outcome of the disease.

The role of microRNA (miR)200c-3p in regulating ACE2 gene expression in viral and bacterial respiratory diseases has been established. Since ACE2 reduces the acute inflammatory effects in lung diseases and acts as a coronavirus receptor to invade the lung cells, this study investigates the relationship between miR-200c-3p and ACE2 expression in COVID -19 patients.
In this study, COVID-19 patients were divided into two groups: mild phase (PCR-positive and mild symptoms) and severe phase (PCR-positive with acute pulmonary symptoms and inflammation). Then, the subjects' demographic, clinical, and paraclinical characteristics were recorded using a prepared checklist. Total RNA was isolated from all samples according to the Trizol kit protocol to evaluate gene expression. Subsequently, the extracted product was analysed for miR-200c expression and ACE2 target gene expression by real-time PCR.
The results of the checklist data showed that smoking, cough, and the factors ESR and HCT were statistically significant between the two groups of patients in the mild and acute phases. Also, the mean expression of the miR-200c gene in the mild and acute patients was 1.87±0.70 and 1.87±0.62, respectively, which was not statistically significant. Still, the mean expression of the ACE2 gene, which was 3.96±0.76 and 3.28±0.52 in the mild and acute disease groups, respectively, showed a significant difference between the two groups.
This study showed that the expression levels of ACE2 were significantly reduced in people with severe inflammation compared to people with mild inflammation.

Idiopathic pulmonary fibrosis (IPF) is among the illnesses with a high mortality rate, yet no specific cause has been identified; as a result, successful treatment has not been achieved. Among the novel approaches for treating such hard-to-cure diseases are induced pluripotent stem cells (IPSCs). Some studies have shown these cells’ potential in treating IPF. Therefore, we aimed to investigate the impact of IPSCs on insulin-like growth factor (Igf) signaling as a major contributor to IPF pathogenesis. 
C57BL/6 mice were intratracheally instilled with Bleomycin (BLM) or phosphate-buffered saline; the next day, half of the bleomycin group received IPSCs through tail vein injection. Hydroxyproline assay and histologic examinations have been performed to assess lung fibrosis. The gene expression was evaluated using specific primers for Igf-1, Igf-2, and insulin receptor substrate 1 (Irs-1) genes and SYBR green qPCR master mix. The data have been analyzed using the 2^-ΔΔCT method.
The mice that received Bleomycin showed histological characteristics of the fibrotic lung injury, which was significantly ameliorated after treatment with IPSCs comparable to the control group. Furthermore, gene expression analyses revealed that in the BLM group, Igf1, Igf2, and Irs1 genes were significantly upregulated, which were returned to near-normal levels after treatment with IPSCs.
IPSCs could modulate the bleomycin-induced upregulation of Igf1, Igf2, and Irs1 genes. This finding reveals a new aspect of the therapeutic impact of the IPSCs on IPF, which could be translated into other fibrotic disorders.

Antibiotics are used to treat bacterial liver infections and the resulting inflammation. However, their use is limited due to their side effects, especially the development of antibiotic resistance.
Mesenchymal stem cells (MSCs) are recognized for their immunomodulatory properties. In this study, we investigated the immunomodulatory effect of Wharton's jelly MSC-derived exosomes in combination with imipenem on HepG2 cells infected with Escherichia col
i.MSC-derived exosomes were separated from MSCs, which were isolated by flow cytometry. Scanning electron microscopy and dynamic light scanning were used to confirm the presence of exosomes. Quantitative real-time PCR, ELISA, and nitric oxide assay were used to assess the inflammatory response in the infected cells. Annexin-PI was used to measure the extent of apoptosis.
The results showed that the combination of imipenem and MSC-derived exosomes were more effective than imipenem or exosomes alone in reducing the production and secretion of inflammatory cytokines, nitric oxide, and apoptotic rate in E Coli-infected HepG2 cells.

To investigate the effects of everolimus, a mechanistic/mammalian target of rapamycin (mTOR) inhibitor, on tumor growth and immune response in a mouse model of breast cancer.
Human hormone receptor-positive (HR+)/human epidermal growth receptor 2-negative (HER2-) MC4-L2 cell line was used to establish a mouse model of breast cancer. The inhibitory effects of high (10 mg/kg) and low (5 mg/kg) doses of everolimus were investigated on tumor growth. Additionally, the frequency of CD4⁺Foxp3⁺ regulatory T cells (Tregs), CD8⁺Foxp3⁺ Tregs, and CD4⁺ and CD8⁺ T cells expressing cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) was explored by flow cytometry in bone marrow, lymph nodes, and spleen.
Our results showed that both 10 mg/kg and 5 mg/kg doses of everolimus efficiently inhibited tumor growth, resulting in reduced breast tumor volume. In addition, it was revealed that everolimus-treated mice induced a higher frequency of CD4⁺Foxp3⁺ Tregs, CD8⁺Foxp3⁺ Tregs, and CD4⁺Foxp3⁺CTLA-4⁺ Tregs as well as CD4⁺ and CD8⁺ T cells expressing CTLA-4 in their bone marrow, lymph nodes, and spleen compared with standard control (vehicle-treated) in a dose-dependent manner. Furthermore, we found that everolimus treatment with 10 mg/kg and 5 mg/kg increased the frequency of Helios⁺Foxp3⁺ Tregs in the bone marrow of treated mice compared with the control group.
Our results indicate that treatment with everolimus not only inhibits tumor growth but also exerts an immunomodulatory effect by inducing Tregs in the lymphoid organs of breast cancer-bearing mice. The combination of therapy with other anti-cancer agents may negate immune suppression and improve the efficacy of mTOR-targeted breast cancer therapy.

Dendritic cells (DCs) are a group of bone marrow-derived cells that play a crucial role in innate and acquired immune responses. Bone marrow-derived dendritic cells (BMDC) are used in many studies, so the efficiency and purity of the differentiated cells are essential. This study aimed to investigate the effect of several parameters, including the age of mice, cell culture medium, and swirling of the culture plate, to increase the efficiency of the induced cells, considering the standard protocols.
Bone marrow-derived dendritic cells were induced from both juvenile and adult mice bone marrow cells. Then, the purity of CD11c+ cells was compared between juvenile mice BMDCs and adult mice BMDCs. Cells were cultured in an enriched and non-enriched medium, and some wells were swirled when changing the medium on the 3^rd day. Then the effect of enriched medium and swirling before medium replacement were evaluated based on the expression of the CD11c marker.
The efficiency of DCs differentiation (CD11c⁺ cells) was higher when juvenile mouse bone marrow precursors were used compared to adult mice; using the enriched media with supplements and swirling the well before media replacement significantly affected the purity of immature CD11c⁺ cells.
Due to our results, using juvenile mice, an enriched culture medium, and physical removal of granulocyte cells could significantly improve the purity and efficiency of CD11c⁺ cells. Therefore, considering these three items in the production protocol of these cells can probably reduce the use of lymphocyte-removing antibodies and purification methods.

Thyroid cancer (TC) is the most common endocrine malignancy. Thyroidectomy and radiotherapy are common treatment modalities for patients with undifferentiated TC (UTC), and sorafenib is usually recommended to prevent a recurrence. However, malignant cells may evade chemotherapy-induced apoptosis, and combination therapy was developed to achieve better outcomes. This study investigated whether eugenol in combination with sorafenib was more effective than either substance individually in triggering apoptosis in the UTC.
The IC₅₀ of sorafenib and eugenol was determined in a UTC cell line (8305C) by MTT assay, and their synergistic effect in combination therapy was investigated. Flow cytometry was used to evaluate the rate of apoptosis in treated cells. To confirm that cell death occurred through apoptosis, immunoblotting was used to determine the relative cleavage of caspase-8 and caspase-9.
The IC₅₀ of sorafenib was 20 µM, and that of eugenol was 2100 µM. The sorafenib-eugenol combination (1:105) showed synergistic effects at concentrations equal to or less than their IC₅₀. The rate of apoptosis induction was higher in cells treated with eugenol or the eugenol-sorafenib combination compared to sorafenib-treated cells. The relative intensity of cleaved/un
cleaved forms of caspase-8 increased in eugenol-treated cells compared to sorafenib-treated cells.Sorafenib and eugenol at concentrations equal to or less than their IC₅₀ had a synergistic effect in 8305C cells. The most potent apoptotic effect was achieved with sorafenib and eugenol at their IC₅₀. Lower doses of sorafenib could be used with eugenol to improve its efficacy while reducing its side effects.

Osteoarthritis (OA) is the most common form of arthritis associated with gradual joint destruction. The current treatment aims to alleviate pain and inflammation and improve the quality of life. Crocin is an active ingredient in saffron, with anti-inflammatory properties. MicroRNAs are small, non-coding RNAs that regulate gene expression. We aimed to evaluate the effect of crocin on the gene expression of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 in OA patients and compare it with a placebo.
This study was approved and registered in the Iranian Registry of Clinical Trials (2015021910507N2) and ClinicalTrials.gov identifier: NCT03375814. Forty OA patients were randomly divided into two equal groups, receiving either crocin or placebo. Peripheral blood samples were collected before and four months after the intervention. The pain was assessed using the visual analog scale, and laboratory tests included C-reactive protein and erythrocyte sedimentation rate. The expression levels of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 genes were evaluated by SYBR Green real-time PCR.
The results showed that the gene expression levels of microRNA-21 and microRNA-155 in patients receiving crocin were significantly decreased and increased, respectively. No significant changes were observed in microRNA-146a and microRNA-223 gene expression levels.
In conclusion, crocin's anti-inflammatory role might be partly attributed to its effects on the gene expression of microRNA-21 and microRNA-155.  

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Considering how vitamin B12 or cobalamin affects the immune system, especially inflammation and the formation of the myelin sheath, it appears as a complementary therapy for MS by affecting some signaling pathways.
Recently diagnosed MS patients were divided into two groups (n=30). One group received interferon-beta (IFN-β or Avonex), and another received IFN-β+B12 for six months. Blood samples were taken before and after treatments.  Interleukin (IL)-10 and osteopontin (OPN) levels in the plasma were determined by the enzyme-linked immunosorbent assay (ELISA) method, and the expression of microRNA (miR)-106a, miR-299a, and miR-146a by real-time PCR.
IFN-β neither changed the IL-10 plasma levels nor miR106a and miR-299a expression, but it led to a remarkable decrease in OPN concentration and enhancement in let-7c and miR-146a expression. There was a significant decrease in IL-10, OPN plasma levels, miR-106a expression, and a substantial increase in let-7c and  miR-146a expression in IFN-β+B12, treated group. There was no correlation between IL-10 and OPN with related miRNAs in the two treatment groups.
Our study indicated that B12 could be a complementary treatment in MS that may influence the disease improvement.

Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients.
This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES).
Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN.
Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes.

Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement.
Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. NGS was performed, and the results were confirmed by Sanger sequencing.
Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. This is the first time such mutations are reported and these variants are predicted to be damaging. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis.
Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT).

Fetal hemoglobin is the principal hemoglobin in the human fetus, and the adult levels of fetal hemoglobin (HbF) are less than 1% of total hemoglobin. A steady increase of HbF in patients with hereditary persistence of fetal hemoglobin (HPFH) is associated with complications. The present report describes HPFH in a 26-year-old man with emphasis on its hemoglobin electrophoresis. The patient was admitted with complaints of recurrent weakness and lethargy, weight loss, abdominal pain, and dyspepsia. Splenectomy was planned due to massive splenomegaly and gastrointestinal complications. Ultimately,  electrophoresis confirmed the diagnosis of HPFH.

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