Vol 19 No 6 (2020)


Review Article(s)

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    Several reports have determined that changes in white blood cell counts and inflammatory biomarkers are related to disease outcome of coronavirus disease 2019 (COVID-19) and they can be utilized as prognostic biomarkers. For introducing a factor as a diagnostic/prognostic biomarker, diagnostic test accuracy (DTA) systematic review and meta-analysis are recommended. For the first time, we aimed to determine the accuracies of white blood cell counts and inflammatory biomarkers for prognosis of COVID-19 patient’s outcome by a DTA meta-analysis. Until August24, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to achieve related papers. Summary points and lines of included studies were calculated from 2×2 tables by bivariate/hierarchical models. Critical condition and mortality were considered as outcomes. A total of 13387 patients from 28 studies were included in this study. Six biomarkers containing leukocytosis, neutrophilia, lymphopenia, increased level of C-reactive protein, procalcitonin (PCT), and ferritin met the inclusion criteria. Analysis of the area under the curve (AUCHSROC) indicated that the PCT was the only applicable prognostic biomarker for critical condition and mortality (AUCHSROC=0.80 for both conditions). Pooled-diagnostic odds ratios were 6.78 (95% CI, 3.65-12.61) for prognosis of critical condition and 13.21 (95% CI, 3.95-44.19) for mortality. Other biomarkers had insufficient accuracies for both conditions (AUCHSROC< 0.80). Among evaluated biomarkers, only PCT has good accuracy for the prognosis of both critical condition and mortality in COVID-19 and it can be considered as a single prognostic biomarker for poor outcomes. Also, PCT has more accuracy for the prognosis of mortality in comparison to critical condition.

  • XML | PDF | downloads: 1731 | views: 3891 | pages: 570-588

    The prevalence of multisystem inflammatory syndrome in children (MIS-C) has increased since the coronavirus disease 2019 (COVID-19) pandemic started. This study was aimed to describe clinical manifestation and outcomes of MIS-C associated with COVID-19. This systematic review and meta-analysis were conducted on all available literature until July 3rd, 2020. The screening was done by using the following keywords: (“novel coronavirus” Or COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus) and ("MIS-C" or "multisystem inflammatory" or Kawasaki). Data on gender, ethnicity, clinical presentations, need for mechanical ventilation or admission to intensive care unit (ICU), imaging, cardiac complications, and COVID-19 laboratory results were extracted to measure the pooled estimates. Out of 314 found articles, 16 articles with a total of 600 patients were included in the study, the most common presentation was fever (97%), followed by gastrointestinal symptoms (80%), and skin rashes (60%) as well as shock (55%), conjunctivitis (54%), and respiratory symptoms (39%). Less common presentations were neurologic problems (33%), and skin desquamation (30%), MIS-C was slightly more prevalent in males (53.7%) compared to females (46.3%). The findings of this meta-analysis on current evidence found that the common clinical presentations of COVID-19 associated MIS-C include a combination of fever and mucocutaneous involvements, similar to atypical Kawasaki disease, and multiple organ dysfunction. Due to the relatively higher morbidity and mortality rate, it is very important to diagnose this condition promptly.

  • XML | PDF | downloads: 232 | views: 507 | pages: 589-601

    T helper (Th)-17 cells are a distinct and important subset of Th cells and their functions are due to the ability of production and secretion of key cytokines in the immune system such as interleukin (IL)-17, IL-22, IL-21, and tumor necrosis factor-α (TNF-α). According to these cytokines, these cells have vital roles in the pathogenesis of the disease such as rheumatoid arthritis (RA) and osteoarthritis (OA). Nowadays, microRNAs (miRNAs) are defined as essential regulators of cell function by targeting transcription factors and other elements that act in cells to control gene expression. The purpose of this study was to detect and investigate articles evaluating the function of miRNA in Th-17 cell performance. The language was restricted to English and the search was done in PubMed, Web of Science and Embase. In this review, we first explain the role of effective factors in the function of Th17 lymphocytes, and then, we summarize the performance of several miRNAs involved in the activation and appropriate functions of Th17 cells in the immune system.

Original Article(s)

  • XML | PDF | downloads: 340 | views: 715 | pages: 602-611

    The T-cell immunoglobulin and mucin-3 (TIM-3)/galectin-9 (Gal-9) autocrine loop is an indispensable signaling in acute myeloid leukemia (AML) cells, which induces their self-renewal through activation of nuclear factor-kappa b (NF-kB) and β-catenin pathways. In this study, we evaluated the effects of oridonin and doxorubicin on the TIM-3/Gal-9 autocrine loop. We also evaluated oridonin anti-inflammatory and anti-cancer properties on U937 cells, as an AML cell line in comparison to doxorubicin as a common anthracycline drug for AML treatment. Cell counting kit-8 (CCK-8) was applied to evaluate the cytotoxicity of oridonin and doxorubicin on U937 cells and also to determine the impact of galectin-9 (Gal-9) on their proliferation. The effects of oridonin and doxorubicin on Gal-9, TIM-3, and interleukin-1β (IL-1β) gene expression were determined by real-time polymerase chain reaction (RT-PCR). The Gal-9 secretion level was measured by enzyme-linked immunosorbent assay (ELISA) and activation of NF-kB pathway was assessed by western blotting. In a dose-dependent manner, oridonin and doxorubicin were capable to eradicate U937 cells while Gal-9 expanded them. Following the treatment of U937 cells with oridonin, the expression of Gal-9, TIM-3, and IL-1β genes was down-regulated, and the Gal-9 secretion and NF-kB phosphorylation were diminished, whereas doxorubicin increased all of these factors. Doxorubicin is a common treatment agent in AML, but it may induce inflammation and up-regulate the TIM3/Gal-9 autocrine loop, consequently can enhance the possibility of disease relapse. Meanwhile, oridonin is capable to inhibit the essential signaling pathways in AML cells and reduce the inflammation and expansion of tumor cells and postpone AML recurrence.

  • XML | PDF | downloads: 226 | views: 528 | pages: 612-623

    The potential role of microRNAs (miRNA or MIR) as therapeutic molecules has moved them from basic research to the field of cancer therapy. High expression of miR-93 and low expression of miR-34a have previously been indicated in prostate cancer (PC), which is the second leading cause of cancer-related death in men. Androgen receptor (AR) and prostate-specific antigen (PSA) play key roles in the initiation and progression of this cancer. Therefore, this study aimed to investigate the effects of the transfection and co-transfection of miR-34a mimic and miR-93 inhibitor with or without epigallocatechin-3-gallate (EGCG) on prostate cancer cell line and also to evaluate their effects on the expression of AR, PSA. Human lymph node carcinoma of the prostate (LNCaP) cells were treated with miR-34a mimic or/and miR-93 inhibitor with or without EGCG. Gene or protein expressions were assessed by real-time PCR or western blotting of lysates. The transfection with miR-34a mimics significantly reduced the mRNA expression of AR (p=0.0016), and PSA (p=0.038) compared to the control. Also, the miR-93 inhibitor led to a decrease in the mRNA expression of AR (p=0.0057) and PSA (p>0.05) compared to the control group. Furthermore, the co-transfection, along with EGCG, caused more decrease in both the AR (p<0.001) and the PSA (p=0.003) expression compared with the co-transfection without EGCG. Our study indicates that the reduced expression of AR and PSA in PC cells followed by treatment with miR-34a mimic and miR-93 inhibitor and their combination with EGCG as a natural substance may be a promising therapeutic way for controlling the growth of these malignant cells.

  • XML | PDF | downloads: 187 | views: 375 | pages: 624-631

    Acute organ rejection remains a serious clinical challenge. Novel accessible biomarkers of acute rejection could easily enable us to detect the rejection earlier and make more fine-tuned calibration of immunosuppressive or new target treatment possible. Control of gene expression by microRNAs influences many cellular functions, including cellular differentiation, cell proliferation, cell development, and functional regulation of the immune system. Therefore, this study was aimed to investigate if miRNA146a G>C and miRNA196a-2 C>T gene polymorphisms are associated with kidney transplant rejection in Iranian patients. Tissue samples were collected from 100 renal transplant patients between the years 2009 and 2013. The miRNA146a G>C (rs2910164) and miRNA196a-2 C>T (rs11614913) gene polymorphisms were evaluated in kidney transplant patients; using the in-house-polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In this study, we found that the CC genotype, C and G alleles of the miRNA146a G>C polymorphism was associated with increased risk of transplant rejection in kidney transplant patients (p=0.003, p=0.01 and p=0.01), respectively. The CC genotype, T, and C alleles of the miRNA196a-2 C>T were also significantly more frequent in transplanted patients compared to healthy controls (p=0.02, p=0.05, and p=0.05), respectively. However, significant associations were not found between miRNA196a-2 C>T polymorphisms and kidney transplant rejection. The CC genotype, G, and C allele of the miRNA146a G>C and also, the CC genotype, T and C alleles of the miRNA196a-2 C>T may be genetically susceptible factors for transplant rejection and development of kidney disorders, especially in Iranian patients. Further studies are required to validate these findings in a larger population, as well as in patients with different ethnic origins.

  • XML | PDF | downloads: 197 | views: 500 | pages: 632-639

    Pro-inflammatory cytokines have been suggested in the pathogenesis of idiopathic nephrotic syndrome (INS), with conflicting results. This study was performed to identify alteration of different serum interleukins (ILs) in children with INS, and their predictive value in response to steroid treatment. Three groups of children (27; steroid-sensitive INS, 21; steroid-resistant INS, and 19 healthy controls) with normal serum C3, negative serologic tests of hepatitis B virus (HBV), hepatitis C virus (HCV), human immune deficiency virus (HIV), and parasitic infections were included in this study. Serum concentrations of IL-1β, IL-2, IL-6, IL-8, IL-13, and IL-18 were measured, using quantitative colorimetric sandwich ELISA kits. Children with secondary nephrotic syndrome, inflammations, systemic disorders, and chronic kidney disease were excluded. The serum concentration of all ILs; except IL-13 and IL-18; was significantly higher in children with INS, compared with the healthy controls. Serum IL-2 had the highest sensitivity of (95.24%) in patients with INS. All of the serum ILs had acceptable accuracy in children with INS, compared with the control group. The serum concentration of IL-1β, IL-6, and IL-8 was significantly higher in children with steroid-sensitive nephrotic syndrome (SSNS), compared with steroid-resistant nephrotic syndrome (SRNS). All of these ILs had acceptable accuracy for the prediction of steroid response in patients with INS. Our findings suggested the pathogenic role of pro-inflammatory cytokines in children with INS, of which IL-1β, IL-6, and IL-8 were accurate biomarkers for the prediction of steroid response in these patients.


  • XML | PDF | downloads: 159 | views: 398 | pages: 640-646

    Cesarean section (CS) is an important challenge for a pregnant woman and her newborn. The most common anesthesia techniques used for CS are general anesthesia (GA) and spinal anesthesia (SA). This study was designed to compare the modulation of genes whose expression level is indicative of the immune system following exposure to GA and SA. The present study was performed on 40 women who were scheduled for elective CS receiving GA or SA. The expression levels of the relative mRNA of Interleukin (IL)-4, IL-6, IL-10, IL-17, Interferon (IFN)-γ, and tumor growth factor (TGF)-β before anesthesia (T0) and 24 hours post-anesthesia (T1) were analyzed by real-time polymerase chain reaction (RT-PCR) technique.  Twenty-four hours post-anesthesia, the expression levels of IL-10, IL-17, and IFN-γ genes were decreased while the expressions of IL-4, IL-6, and TGF-β genes were upregulated in two groups, however, the differences were not significant. The mRNA level of IL-4 was increased in the SA group significantly. The post-CS mRNA levels of IL-4 in the SA group may indicate that SA is more appropriate than GA for the initiation of tissue repair pathways.

  • XML | PDF | downloads: 270 | views: 594 | pages: 647-659

    The presence of ambient particulate matter (PM) poses more dangers to human health than that of other common air pollutants such as Carbon dioxide (Co2) and ozone.  Epidemiologic studies show a direct correlation between PM and the risk of respiratory and cardiovascular diseases. The immune system seems to play a critical role in the process of these diseases. The main goal of this study was to investigate the effect of Tehran particulate matter in two aerodynamic diameters (PM2.5 and PM10) on alveolar macrophages (AM) from C57/BL6 mice. To evaluate the inflammatory effects of PMs, cultured alveolar, and peritoneal macrophages were treated with PM2.5 and PM10 (concentrations of 5 µg/mL and 10 µg/mL). Tumor necrosis factor-alpha (TNF-α) and IL-10 (representatives of inflammatory and anti-inflammatory cytokines, respectively) were assessed in the culture supernatant by ELISA. Expression of arginase and inducible nitric oxide synthase (iNOS) genes was carried out by quantitative real-time PCR. Different functional types of cultured alveolar macrophages (M1, M2) were also determined in this study. Our results suggest that PM2.5 induces M1 inflammatory phenotype in comparison with PM10. We found Also, an increase in TNF-α and M1-related gene expression (iNOS), as well as a decrease in both IL-10 and M2 phenotype genes (Arginase). Moreover, a reduction in phagocytic capacity and increased apoptosis function of macrophage cells were detected. PM2.5 as a major component in hydrocarbons has a considerable effect on polarizing the alveolar macrophages to an inflammatory phenotype and eliciting lung inflammation in mice.

Brief Communication

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    Asthma is the most common chronic inflammatory respiratory disorder in children. This study was designed to assess the prevalence of asthma in 13-14-year-old adolescents in Karaj, Alborz province in Iran, using the international study of asthma and allergies in childhood (ISAAC) questionnaire. Totally 950 adolescents attending 40 schools located in 4 regions of Karaj city were enrolled in the survey. The Persian version of the ISAAC questionnaire was filled by 13-14-year-old students. Multi-stage clustered random sampling was used to divide the city of Karaj into four educational districts. Ever wheezing was reported in 22% of the individuals; 10.52% claimed to have wheeze in the last 12 months and 22.73% had during or after exercise. The experience of wheezing in the last 12 months was more prevalent among males (11.73% vs. 9.38%; p<0.05). However, having a history of asthma was higher among males (7.55% vs. 3.47%; p<0.05). History of hospitalization (60.8%), family history of asthma (49.4%), and history of food allergy (42.3%) were found to be the most frequent characteristics significantly associated with" ever wheezing" (p<0.05). The prevalence of wheezing in the last 12 months, as a major index of current asthma, was 10% which was close to the national average. However, nocturnal cough and exercise-induced wheezing were higher in Karaj compared to other cities of Iran; which could be related to the high level of air pollution in this industrial area.

Case Report(s)

  • XML | PDF | downloads: 228 | views: 426 | pages: 667-675

    Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) gene causes autosomal dominant hyper immunoglobulin E syndrome (AD-HIES or Job’s Syndrome), a rare and complex primary immunodeficiency (PID) syndrome characterized by increased levels of IgE (>2000 IU/mL), eosinophilia, recurrent staphylococcal skin abscesses, eczema, recurrent pneumonia, skeletal and connective tissue abnormalities. Although bacterial and fungal infections are common in AD-HIES, susceptibility to parasitic infections has not been reported. Alveolar echinococcosis (AE), a zoonosis caused by the growth of the Echinococcus multilocularis (EM) metacestode, mimics slow-growing liver cancer. The mortality rate of AE is very high when it is diagnosed late or under-treated. Here, we report a 14-year-old boy with AE infections of the liver and the lung resulting in liver failure and diagnosed as STAT3-LOF. To our knowledge, the association between these two conditions has not been reported in the literature before.