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Additional file 1: Fig. S1: Frequency of type of malignancy based on the IUIS classification. Table 1: Immunodeficiencies affecting cellular and humoral immunity, Table 2: Combined immunodeficiencies with associated or syndromic features, Table 3: Predominantly antibody deficiencies, Table 4: Diseases of immune dysregulation, Table 6: Defects in intrinsic and innate immunity. Fig. S2: Survival analysis of cohort of 82 IEI patients with malignancies based on the IUIS classification. Table 1: Immunodeficiencies affecting cellular and humoral immunity, Table 2: Combined immunodeficiencies with associated or syndromic features, Table 3: Predominantly antibody deficiencies, Table 4: Diseases of immune dysregulation, Table 6: Defects in intrinsic and innate immunity.

SARS-CoV-2 is a type of beta-CoV that develops acute pneumonia, which is an inflammatory condition. A cytokine storm has been recognized as one of the leading causes of death in patients with COVID-19. ALI and ARDS along with multiple organ failure have also been presented as the consequences of acute inflammation and cytokine storm. It has been previously confirmed that SARS-CoV, as another member of the beta-CoV family, activates NLRP3 inflammasome and consequently develops acute inflammation in a variety of ways through having complex interactions with the host immune system using structural and nonstructural proteins. Numerous studies conducted on Tranilast have further demonstrated that the given drug can act as an effective anti-chemotactic factor on controlling inflammation, and thus, it can possibly help the improvement of the acute form of COVID-19 by inhibiting some key inflammation-associated transcription factors such as NF-κB and impeding NLRP3 inflammasome. Several studies have comparably revealed the direct effect of this drug on the prevention of inappropriate tissue’s remodeling; inhibition of neutrophils, IL-5, and eosinophils; repression of inflammatory cell infiltration into inflammation site; restriction of factors involved in acute airway inflammation like IL-33; and suppression of cytokine IL-13, which increase mucosal secretions. Therefore, Tranilast may be considered as a potential treatment for patients with the acute form of COVID-19 along with other drugs.

Introduction: In COVID-19 patients, those with underlying disease are relatively more susceptible to respiratory viral infections and are more likely to develop severe symptoms compared to people without underlying disease. Objectives: This study aimed to evaluate the serum levels of interleukin (IL)-8 and IL-17 in patients infected with severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) and patients with underlying disease. Patients and Methods: Serum samples were collected before administration of any antiviral and/or immunosuppressive drug. Around 64 adult patients with COVID-19 and 12 adult patients with underlying disease were compared with 16 healthy subjects as controls. The cytokine levels were assessed by ELISA (enzyme-linked immunosorbent assay) method and the statistical analysis was carried out using the one-way analysis of variance (ANOVA). Results: The average levels of these cytokines in the severe group were significantly higher than those in the mild and control group (r=0.48, P

This review gives a summary of the important genetic polymorphisms in breast cancer with a focus on people in Iran. Several single nucleotide polymorphisms were considered as breast cancer susceptibility polymorphisms within genes ( STK15, ERRs, ESR1, p53, SEP15, AURKA, SHBG, SRC, FAS, VEGF, XRCC1, GST, NFκB1, XPC, XRCC3, sirtuin-3, NKG2D). Cytosine–adenine repeat (IGF-I), rs3877899, G-2548A, GGC (eRF3a/GSPT1), IVS2nt-124A/G have shown an increased risk of breast cancers and a decreased risk has been observed in 4G/5G (PAI-1), rs6505162, tri-nucleotide ( GCG TGFBR1). We observed that the signaling pathways and antioxidant related genes are the main molecular processes associated with breast cancer progression. Further studies on types of polymorphisms in breast cancer could validate the prognostic value of biomarkers.

Chloroquine and hydroxychloroquine belong to the aminoquinoline drugs. Studies revealed that chloroquine and hydroxychloroquine shows antagonism activity against COVID-19 under laboratory conditions. ARDS and ALI are conditions that occur in patients with COVID-19 as the main pathological complications of cytokine storm. Inflammasomes play a key role in the pathogenesis of many diseases associated with destructive inflammation. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The possible role of NLRP3 inflammasome inhibitors in the treatment of COVID-19 has been considered. We surveyed the potential inhibitory effect of chloroquine and hydroxychloroquine on inflammasome. Studies indicate that one of the possible anti-inflammatory mechanisms of chloroquine and hydroxychloroquine is inhibition of the activity of NLRP3 inflammasome.

Polycystic ovary syndrome (PCOS) involves abnormalities in ovarian, reproductive, and metabolic systems. Genetic polymorphisms associated with individual differences and variations might be related to complex disorders with unknown causes, including PCOS. Several leading genetic markers with known cellular functions have been identified among Iranian women presenting with PCOS. In particular, the existing evidence shows a significant relationship between PCOS and the following genetic polymorphisms: rs2275913 (interleukin-17A), rs9927163 (interleukin-32), Pro12Ala (peroxisome proliferator-activated receptor-γ), rs17173608 (chemerin), rs2236242 (vaspin), ApaI (vitamin D receptor), and rs7895833 (sirtuin 1). In addition, a higher risk of PCOS is associated with the rs2910164 (microRNA 146a), rs2241766 (adiponectin), -34 T/C (cytochrome 17), and rs1800682 (Fas) polymorphisms. Furthermore, protective effects against PCOS have been reported for the A4223C polymorphism of adenosine deaminase 1. Overall, the available data indicate that Iranian women with PCOS have a higher prevalence of polymorphisms in inflammation- and metabolism-related genes, but not in insulin-related genes. More extensive studies are needed to identify the ethnicity-related genetic associations in PCOS.

Following the outbreak of the COVID-19 pandemic, millions of people around the world have been affected with SARS-CoV-2 infection. In addition to the typical symptoms, thrombotic events, lymphopenia, and thrombocytopenia have been reported in COVID-19 patients. Immune thrombocytopenic purpura (ITP) is one of the thrombotic events that occur in some COVID-19 patients. Hyperinflammation, cytokine storms, and immune dysregulation in some patients are the cause to the main COVID-19 complications such as ALI (acute lung injury), acute respiratory distress syndrome (ARDS), and multiple organ failure. Disruption in the differentiation of T-cells, enhanced differentiation of Th17 and Th1, cell death (pyroptosis), hyper-inflammation and dysfunction of inflammatory neutrophils and macrophages, and hyperactivity of NLRP3-inflammasome are among the important factors that may be the cause to COVID-19-induced ITP. This study aimed to give an overview of the findings on the immunopathogenesis of ITP and COVID-19-induced ITP. Further studies are required to better understand the exact immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders.

Millions of people around the world were, or are still involved with COVID-19 due to infection with SARS-CoV-2. In addition to hallmark symptoms, thrombotic problems, lymphopenia, and thrombocytopenia have also been reported in COVID-19 patients, of which ITP is the most common and occurs in more than one-third of COVID-19 patients. Hyperinflammation, cytokine storms, and generally immune dysregulation in a percentage of patients develop the main consequences of diseases such as ALI, ARDS and multiple organ failure. Some of the important events in the immunopathogenesis of this disease are disruption of T-cell effector differentiation and the destructive role of Th17 lymphocytes, neutrophil function and inflammatory macrophages. NLRP3-inflammasome hyperactivity causes serious dysfunction of innate immune cells and, consequently, T lymphocytes in many inflammatory disorders, most notably in the COVID-19. A closer look at the immunopathogenesis of ITP and COVID-19 brings us to common ground. The purpose of this study was to review and summarize the findings of various studies on the immunopathogenesis of ITP and its possible causes in COVID-19. Finally, enhanced differentiation of Th17 and Th1, the cell death called as pyroptosis, hyperinflammation and dysfunction of inflammatory neutrophils and macrophages, and NLRP3- inflammasome hyperactivity are important factors in the development of thrombocytopenia in patients with COVID-19. Further studies are needed to better understand immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders

Millions of people around the world are involved with COVID-19 due to infection with SARS-CoV-2. Virological features of SARS-CoV-2, including its genomic sequence, have been identified but the mechanisms governing COVID-19 immunopathogenesis have remained uncertain. miR-223 is a hematopoietic cell-derived miRNA that is implicated in regulating monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses. The miR-223 controls inflammation by targeting a variety of factors, including TRAF6, IKKα, HSP-70, FOXO1, TLR4, PI3K/AKT, PARP-1, HDAC2, ITGB3, CXCL2, CCL3, IL-6, IFN-I, STMN1, IL-1β, IL-18, Caspase-1, NF-κB, and NLRP3. The key role of miR-223 in regulating the inflammatory process and its antioxidant and antiviral role can suggest this miRNA as a potential regulatory factor in the process of COVID-19 immunopathogenesis.

The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1β in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1β, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1β cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.

Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between benign and malignant ones in terms of pathological characteristics, as well as lack of appropriate molecular markers; significant efforts are being made to identify molecular markers that able to detect tumorous lesions. Survivin, the newest member of the family of proteins inhibiting cell apoptosis, has been recently considered as a novel molecule marker for cancer. Studies on TC have also demonstrated distinctive expression of survivin and its splice variants in cancer cells compared to normal ones. Therefore, detection of survivin expression and its new splice variants can be utilized to identify tumor nodules and distinguish them from non-cancerous ones, along with other routine laboratory methods.

SARS-CoV-2 is a betacoronavirus causing severe inflammatory pneumonia, so that excessive inflammation is considered a risk factor for the disease. According to reports, cytokine storm is strongly responsible for death in such patients. Some of the consequences of severe inflammation and cytokine storms include acute respiratory distress syndrome, acute lung injury, and multiple organ dysfunction syndromes. Phylogenetic findings show more similarity of the SARS-CoV-2 virus with bat coronaviruses, and less with SARS-CoV. Quercetin is a carbohydrate-free flavonoid that is the most abundant flavonoid in vegetables and fruits and has been the most studied to determine the biological effects of flavonoids. Inflammasomes are cytosolic multi-protein complexes assembling in response to cytosolic PAMP and DAMPs, whose function is to generate active forms of cytokines IL-1β and IL-18. Activation or inhibition of the NLRP3 inflammasome is affected by regulators such as TXNIP, SIRT1 and NRF2. Quercetin suppresses the NLRP3 inflammasome by affecting these regulators. Quercetin, as an anti-inflammatory, antioxidant, analgesic and inflammatory compound, is probably a potential treatment for severe inflammation and one of the main life-threatening conditions in patients with COVID-19.

Aim: To evaluate the clinical efficacy of adjuvant use of melatonin in patients with coronavirus disease 2019 (COVID-19). Methods: This single-center, double-blind, randomized clinical trial included 74 hospitalized patients with confirmed mild to moderate COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from April 25, 2020 to June 5, 2020. Patients were randomly assigned in a 1:1 ratio to receive standard of care and standard of care plus melatonin at a dose of 3 mg three times daily for 14 days. Clinical characteristics, laboratory, and radiological findings were assessed and compared between two study groups at baseline and post-intervention. Safety and clinical outcomes were followed up for four weeks. Results: A total of 24 patients in the intervention group and 20 patients in the control group completed the treatment. Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved (P < 0.05). The mean time of hospital discharge of patients and return to baseline health was significantly shorter in the intervention group compared to the control group (P < 0.05). No deaths and adverse events were observed in both groups during this study. Conclusions: Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health. Keywords: COVID-19, Melatonin, Clinical trial, Adjunctive therapy Trial Registration: ClinicalTrials.gov Identifier: NCT04409522

Curcumin is the effective ingredient of turmeric, sometimes used as a painkiller in traditional medicine. It has extensive biological properties such as anti-inflammatory and antioxidant activities. SARS-CoV-2 is a betacoronavirus developing severe pneumonitis. Inflammasome is one of the most important components of innate immunity, which exacerbates inflammation by increasing IL-1β and IL-18 production. Studies on viral infections have shown overactivity of inflammasome and thus the occurrence of destructive and systemic inflammation in patients. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The proliferation of SARS-CoV-2 in a wide range of cells can be combined with numerous observations of direct and indirect activation of inflammasome by other coronaviruses. Activation of the inflammasome is likely to be involved in the formation of cytokine storm. Curcumin regulates several molecules in the intracellular signal transduction pathways involved in inflammation, including IBB, NF-kBERK1,2, AP-1, TGF-β, TXNIP, STAT3, PPARγ, JAK2-STAT3, NLRP3, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Due to anti-inflammatory and anti-inflammasome properties without any special side effects, curcumin can potentially play a role in the treatment of COVID-19 infection along with other drug regimens.

The definition of an exclusive panel of genetic markers is of high importance to initially detect among this review population. Therefore, we gave a summary of each main genetic marker among Iranian patients with thyroid cancer for the first time which were classified based on their cellular function. Due to the results, a significant relationship was found between SNP in codons 194, 280, and 399 (XRCC1), Allele 3434Thr (XRCC7), GC or CC genotype 31, G/C (Survivin), 399G>A (XRCC1), Tru9I (vitamin D receptor), G‐D haplotype (MDM2), TT genotype, −656 G/T (IL-18), TAGTT haplotype (IL-18), G allele in +49 A>G (CTLA-4), +7146 G/A (PD-1.3), +7785 C/T (PD-1.5), rs1143770 (let7a‐2), rs4938723 (pri‐mir‐34b/c) genes, and thyroid cancers. Moreover, SNP in 677C-->T (MTHFR), GG genotype Asp1312Gly (thyroglobulin), 2259C>T (Rad52), R188H, (XRCC2), T241M (XRCC3) had higher risks of thyroid cancer and lower risks were observed in −16 Ins-Pro (p53), rs3742330 (DICER1). At last, the protective effects were explored in 127 CC genotype (IL-18), rs6877842 (DROSHA). Conduct further studies on the types of DNA repair gene polymorphisms with a larger number in the thyroid cancer using modern methods such as SNP array so that these genes could be used as a biomarker in prediction, diagnosis, and treatment of thyroid cancer. This review presents for the first time a summary of important genetic markers in Iranian patients with thyroid cancer.