Recently, the era of medicine has been encountered with the exponential growth of special seroimmunobiomarkers in clinical trials. Lately, Interleukin-37 (IL-37) has attracted a wide range of basic medical scientists’ attention due to its controversial functions in physiologic or pathologic microenvironments. In this research, an updated overview of immunobiological functions and clinical applications of IL-37 in a wide range of diseases, are discussed in order to highlight the role of recent laboratory-based results of IL-37.
Data of this systematic review article were collected from initial 237 articles in Google Scholar search engine, Science Direct, PubMed, Scopus, and Embase databases. Eventually, 134 total articles were considered from March 2000 to June 2019 time interval, by using 5 keywords. Relevant English articles, abstracts and conference papers all were included. No restrictions of methods and type of the article were imposed.
As one of the newly immunotherapeutic based approaches, clinical applications of cytokines are promisingly taken into account for diagnosis and treatment of multiple diseases. Various evidence suggests that IL-37 has notable roles in the regulation of acute and chronic inflammatory responses. Also, IL-37 has been studied in pregnancy, obesity, infectious, cardiovascular, neurologic, autoimmune, and metabolic diseases. Also, the protective functions of IL-37 against multiple cancers, are disputably related to the type and stage of cancer as well as the IL-37 variant.
The broad spectrum of IL-37 and its receptors in diseases, seem to be a potential candidate with pivotal effects for immunomodulation and immune gene therapy of various pathologic states.

There are many pieces of evidence support the effect of cancer stem cells on the initiation and progression of cancer. However, related mechanisms involved in these phenomena are far more complicated to understand. The function of different stemness factorsin cancer stem cells (CSCs) and their complex associations at different levels of cancer have been reported. Therefore, it seems that focusing on one master factor would be more helpful to complete the puzzle of singling pathways in these cells. Octamer-binding transcription factor 4 (OCT4) also known as POU domain, class 5, transcription factor 1(POU5F1), one of these key pluripotency factors, has important roles in both embryogenesis and tumorigenesis.
In this review, we gathered information about the association of different markers with OCT4 expression in three types of gastrointestinal cancers including esophageal, gastric and colorectal cancers.
OCT4 through different signaling pathways has an impact on different processes of gastrointestinal cancers such as proliferation, invasion, and metastasis.
Based on the literature, OCT4 has great effects on cancer progression at different stages, therefore we suggested it has potential implications in therapeutic options.

Knee osteoarthritis (OA) is one of the common degenerative articular disorders that are related to decreased quality of life. Currently, novel biologic therapeutic approaches are introduced in the literature for OA management. In this study, the clinical efficiency of Dextrose prolotherapy, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) injection on the level of pain and function in Knee OA were compared.
A randomized clinical trial was directed on 92 knee OA patients. Patients were randomly divided into three groups: 30 were received dextrose prolotherapy once in a week for three weeks, 30 received autologous PRP for two times with seven days interval, and in the remaining 32 patients 2ml of ACS were injected two times every seven days. Study participants were measured through the Western Ontario and McMaster Universities (WOMAC) score, the visual analogue scale (VAS), at baseline, 1 and 6 months post-intervention.
Both ACS and PRP treated patients showed improvement in pain intensity and knee function during 1 and 6 months pursue; however, this progress was more significant in the ACS group. Dextrose prolotherapy showed no substantial changes in pain and function of the affected knee in treated patients.
Treatment of Knee OA with ACS and PRP injections are associated with pain reduction and knee function improvement. Not only, ACS therapy is more effective than that of PRP, but also due to its less variability in processing and less reported side effects, it could be considered as a safe and effective non-surgical alternative for OA management.

Osteoarthritis (OA) is the major cause of joint pain and disability. This research was planned to examine the effects of Krocina™, aherbal medicine made of crocin, an ingredient of saffron, in patients with OA.
Forty patients suffering from OA were enrolled in our study and randomly divided into two groups, receiving Krocina™ and placebo, and the clinical trial continued for four months.Peripheral blood was taken from all patients and the percentage ofvarious subsets of T cells in addition to the levels of forkhead box protein P3 (FOXP3) and interleukin (IL)-17 were measured by flow cytometry technique.
The visualan alog scale (VAS) index analysis decreased significantly in both groups (krocina^TM and placebo) (p<0.05). Assessment of the C-reactive protein (CRP) level in serum showed a significant decrease in the krocina^TM group (p<0.05). Moreover, we found a meaningful increase in the percentage of regulatory T cells (Tregs)cellin samples gathered from Krocina™ group (P=0.02) patients. The mean percentages of T helper (Th) 17 cellsinthe Krocina™ group and CD8+ T cellsin the placebo group patients were also meaningfully reduced (p<0.05). The geometric mean fluorescence intensity (GMFI) for IL-17 showed a significant decrease and increase in Krocina™ and placebo groups, respectively (p<0.05). No noticeable difference was observed in the percentages of Th cells and GMFI-FOXP3 in either group. Treg/Th17 ratio was shifted towards Tregscell in Krocina™ group at the end of the intervention.
It is concluded that Krocina™ has immunoregulatory effects on patients with OA, ameliorating the disease.

Chimeric antigen receptor (CAR) T cell therapy is considered as an encouraging approach for the treatment of hematological malignancies. However, its efficacy in solid tumors has not been satisfying, mainly in the immunosuppressive network of the tumor microenvironment and paucity of appropriate target antigens. Mesothelin (MSLN) is a tumor-associated antigen (TAA) expressed in numerous types of solid tumors such as gastrointestinal, ovarian, and pancreatic tumors. Owing to high expression in tumor cells and low expression in normal tissues, MSLN-targeted therapies like monoclonal antibodies have been previously developed.
In the present study, a CAR T cell harboring the second-generation of a fully human anti-MSLN-CAR construct containing CD3ζ and 4-1BB signaling domains was produced and it was functionally evaluated against an MSLN-expressing cell line.
The findings showed potent, specific proliferation, cytotoxic activity, and interleukin (IL)-2, Tumor necrosis factor-(TNF) α, and Interferon-(IFN) γ production in an antigen-dependent manner. Cytotoxic activity was shown in effector-to-target ratio from 1:1 to 20:1, but the most adequate efficacy was observed in the ratio of 10:1. Non-specific activity against MSLN negative cell line was not observed.
Our data demonstrated that primary human T cells expressing fully human MSLN-CAR construct are effective against MSLN-expressing cell lines in vitro, suggesting this MSLN-CAR construct as a potential therapeutic tool in a clinical setting.

Chenopodium album polcalcin (Che a 3) is characterized as a major cause of cross-reactivity inallergic patients to the Chenopodiaceae family. Therefore, the present study was conducted to develop a hypoallergenic Che a 3 derivatives as the candidate vaccine for type 1 allergy.
Four derivatives were generated from Che a 3. The first was a mosaic peptide derivative computationally identified in Che a 3 which was coupled to keyhole limpet hemocyanin (KLH). The second one was a mutant Che a 3, and the other two derivatives included N- and C-terminal halves of Che a 3 that both coupled to KLH. The IgE-binding capacity of Che a 3 and its derivatives and also their ability to induce there combinant Che a 3 (rChe a 3)-specific IgG antibody, were determined using the enzyme-linked immune sorbent assay (ELISA). Moreover, the lymphopro liferative capacity of rChe a 3 or its derivatives and their pro-inflammatory cytokine response interleukin (IL)-5 and IL-13 were measured in the human peripheral blood mononuclear cells (PBMCs).
Among all derivatives, the N-terminal half peptide and mosaic peptide exhibited the lowest IgEbinding capacity. In addition, in comparison to other antigens, KLH-coupled mosaic peptide induced the highest level of the recombinant Che a 3 (rChe a 3)-specific IgG antibody and ther Che a 3 specific-blocking IgG antibody in mice. Moreover, the mosaic peptide lacked lymphopro liferative capacity and down-regulated expression of pro-allergic IL-5 and IL-13 cytokines.

Asthma is a common airway inflammation with an intricate underlying mechanism. The role played by circulating miRNAs in asthma remains unclear. In the present study, we aimed to investigate the role of miR-223-3p in leukocytes of asthma and identify the relationship between miR-223-3p and inflammatory cytokines in asthma.
Using real-time polymerase chain reaction (RT-PCR), we detected miR-223-3p expression in peripheral blood leukocytes from 23 asthmatic patients and 20 healthy controls. The levels of IFN-γ (Th1 cytokine), IL-4 (Th2 cytokine), IL-17A (Th17 cytokine) in plasma were examined using enzyme-linked immunosorbent assay (ELISA). Analysis of variance (ANOVA) and Spearman’s test was used for statistical analysis.
The expression of miR-223-3p in peripheral blood leukocytes was upregulated in the asthmatic patients compared with that in the healthy controls. Increased miR-223-3p expression was associated with forced expiratory volume in 1-second percent predicted (FEV1% predicted). A positive correlation was noted between miR-223-3p and IL-17A.
The findings of this study showed that miR-223-3p plays a vital role in the pathogenesis of asthma and can serve as a novel biomarker for asthma.

Matrix metalloproteinases (MMP)-9 facilitates the migration of T-cells to central nervous system (CNS), while tissue inhibitor of metalloproteinases-1(TIMP-1) inhibits the function of MMP-9. This study aimed to determine the appropriate treatment option for multiple sclerosis (MS).
Forty-three relapsing-remitting MS (RRMS) patients were randomly divided into two groups of 22 (group A, placebo) and 21 (group B, Saffron pill) individuals. Serum samples were collected from patients’ blood before using the Saffron pills/placebo pills and then after 12 months. The serum level of MMP-9 and its inhibitor, as well as TIMP-1, were measured by ELISA kits.
MMP-9 serum levels noticeably decreased in patients with MS following 12 months of treatment with Saffron pills (p=0.006) while the changes were not significant before and after 12 months of treatment with placebo pills. Although the levels of TIMP-1 increased significantly after one year treating with Saffron pills (p=0.0002), a considerable difference was not observed before and after taking the placebo pills.
The study finding revealed that 12-months treatment with Saffron could have a significant role in reducing the serum level of MMP-9 and increasing the serum level of TIMP-1 in RRMS patients. Therefore, modulating the serum levels of MMP-9 as an important regulator of T cell trafficking to the CNS might be a promising strategy in the treatment of MS patients.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by genetic defects in the Bruton tyrosine kinase (Btk) gene. XLA is characterized as an antibody deficiency by recurrent bacterial infections, the absence of peripheral B cells, and profound reductions in all immunoglobulin isotypes. This study aims to report the clinical and genetic features of five Iranian patients with XLA.
Five male cases with recurrent bacterial infection entered this study based on clinical evaluation and Immunological screening tests. The levels of T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) were also measured in dried blood spot (DBS) samples. Sanger sequencing was applied to PCR products of DNA samples of the patients for genetic studies.
All patients were from unrelated families with a mean age of 6.7 years (2.5-11) at the time of diagnosis with 4.8 mean years of delay in diagnosis. The most frequent clinical manifestations were recurrent respiratory infections and arthritis. In these patients, five previously reported mutations were found including four mutations (p.Q496X, p.Q497X, p.R520X, and p.R641H) in the Kinase domain besides one mutation (p.L37P) in the pleckstrin homology (PH) domain. Evaluations of KREC and TREC level in patients’ DBS showed low-to-undetectable copies of KREC (0-2 copies/3.2mm DBS) with normal copies of TREC.
As patients with XLA have complete immunoglobulin defects and develop severe and recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. The study results may provide valuable information for the diagnosis, genetic counseling and prenatal diagnosis for the patients and their family members and emphasize performing KREC as an early diagnostic test in patients with XLA.

Hen’s egg, as one of the most common reasons for IgE-mediated food hypersensitivity, affects both children and adults. Taking precautionary measures is suggested for the consumption of other birds’ eggs for patients with allergy to hen’s egg. This paper describes a rare patient with quail egg allergy, which manifested no allergic reactions after oral food challenge with hen’s egg white.

Autoimmune polyendocrine syndrome type 1 (APS1) is a scarce polyendocrinopathy with autosomal recessive inheritance results from defects in the human autoimmune regulatory (AIRE) gene. In addition to three major manifestations of APS1 including mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease, ophthalmic problems such as keratoconjunctivitis, dry eye, iridocyclitis, and cataract can be seen in these patients. In this article, we introduced two siblings presented with nail dystrophia, severe photophobia, and keratitis since early childhood which genetic examination revealed single nucleotide T>C translocation in their 2nd exon and heterozygous deletion mutation in their 12th exon.

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