فهرست مطالب

  • Volume:7 Issue: 28, 2019
  • تاریخ انتشار: 1397/10/28
  • تعداد عناوین: 7
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  • Masoud Najafi, Alireza Shirazi*, Elahe Motevaseli, Ghazale Geraily, Peyman Amini, Dheyauldeen Shabeeb, Ahmed Eleojo Musa Pages 1-6
    Lung injury is one of the major concerns for chest cancer patients that undergo radiotherapy as well as persons exposed to an accidental radiological event. Reduction/oxidation (redox) system plays a key role in lung injury via chronic upregulation of pro-oxidant enzymes. NOX2 and NOX4 are two important reactive oxygen species generating enzymes that are involved in radiation toxicity in some organs such as the bone marrow. In this study, we aimed to evaluate the expression of NOX2 and NOX4 signaling in rat’s lung tissues. Upregulation of these genes may be involved in radiation-induced lung injury. Moreover, we evaluated the role of pre-treatment with melatonin on the expression of these genes. Twenty male rats were divided into 4 groups as control; melatonin treated; irradiation; and irradiation with melatonin pre-treatment. Rats were exposed to 15 Gy 60Co gamma rays and sacrificed after 10 weeks for evaluation of NF-κB, TGFbR1, SMAD2, NOX2, and NOX4 genes expression by real-time PCR. Results showed the upregulation of all five genes. The expression of NOX2 was more obvious compared to other genes. Administration of melatonin before irradiation could attenuate the expression of all mentioned genes. Results indicate that upregulation of NADPH oxidase genes such as NOX2 and NOX4 may be involved in the late effects of lung exposure to ionizing radiation. Melatonin via downregulation of these pro-oxidant genes is able to attenuate radiation toxicity in the lung.
    Keywords: Radiation, Lung, NOX2, NOX4, TGFR1, SMAD2
  • Paiman Amini, Hana Saffar, Elahe Motevaseli, Masoud Najafi, Ramezan Ali Taheri, Ali Qazvini, Mohammad Reza Nourani* Pages 7-14
    Radiation-induced lung injury is one of the most prominent factors that interfere with chest cancer radiotherapy, and poses a great threat to patients exposed to total body irradiation. Upregulation of pro-oxidant enzymes is one of the main mechanisms through which the late effects of ionizing radiation on lung injury can be exerted. Interleukin (IL)-4 and IL-13 are two important cytokines that have been proposed to be involved in this process. Through stimulation of dual oxidase 1 and 2 (DUOX1 & 2), they induce chronic oxidative stress in irradiated tissues. In this study, we evaluated the effects of curcumin treatment on the regulation of IL-4 and IL-13, DUOX1 & 2 genes as well as the pathological changes developed by this treatment. Twenty male Wistar rats were divided into four groups: radiation only; curcumin only; radiation + curcumin; and control group with neither pharmacotherapy nor radiation. Curcumin was administered for 4 and 6 consecutive days before and after irradiation, respectively. Also, the chest area was irradiated with 15 Gy using a cobalt-60 gamma rays source. All rats were sacrificed 67 days after irradiation followed by assessment of the levels of IL-4 and IL-13; the expression of IL-4 receptor-a1 (IL4Ra1), IL13Ra2, DUOX1 and DUOX2, and finally the histopathological changes were evaluated. Radiation led to the increased level of IL-4, while the level of IL-13 showed no change. QPCR results showed the upregulation of IL4Ra1, DUOX1 and DUOX2 following lung irradiation. Histopathological evaluation also showed a remarkable increase in pneumonitis and fibrosis. Treatment with curcumin downregulated the expression of IL-4, IL4Ra1, DUOX1 & 2. Furthermore, it could mitigate pneumonitis and fibrosis following lung irradiation. The late effects of radiation-induced lung injury may be due to the upregulation of DUOX1 & 2 genes. Curcumin, through modulation of these genes, may contribute to the protection against ionizing radiation.
    Keywords: Curcumin, radiation, radioprotection, DUOX1, DUOX2
  • Muge Molbay, Dijle Kipmen, Korgun, Gizem Korkmaz, Murat Ozekinci, Emin Korgun* Pages 15-23
    Trophoblast stem cells develop from polar trophoectoderm and give rise to the cells that generate the placenta. Trophoblast cells are responsible for the uterinal invasion and vascular remodeling during the implantation of the embryo. However this knowledge is not yet to be confirmed for trophoblast progenitor cells (TPCs). In this study, we aimed to demonstrate that human TPCs (hTPCs) express and release angiogenic factors for the first time. TPCs were isolated from the term placenta. Then immunophenotyping was performed by FACS method by analyzing caudal type homeobox 2 (CDX2) and eomesodermin (EOMES). Immunofluorescence staining of CDX2 and EOMES was performed on these cells. Lastly, angiogenesis-related proteins were detected by western blot and ELISA assays. The isolated cells were positive for trophoblast stem cell markers CDX2 and EOMES in 92.5% and 92.7% of cells, respectively showing the characteristics of TPCs. The investigation of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (VEGFR1), and vascular endothelial growth factor receptor 2 (VEGFR2) at protein and mRNA level in comparison with human umblical vein endothelial cells (HUVECs),  revealed that human TPCs (hTPCs) have higher levels of VEGF and VEGFR1 transcripts. Additionally soluble forms of VEGF and VEGFR1 were detected in supernatants of hTPCs. With this information, TPCs seem to be promising for regenerative cell therapies by increasing angiogenesis.
    Keywords: Trophoblast progenitor cells, angiogenic factors, CDX2, EOMES
  • Naghi Dara, Shahram Nemati, Shahram Teimourian*, Farid Imanzadeh, Amirhossein Hoseini, Saleheh Tajalli, Ali Aakbar Sayyari, Ali Najafi, Pejman Rohani, Katayoun Khatami, Elahe Motevaseli, Martin De Boer, Taco W. Kuijpers Pages 24-30
    Inflammatory bowel disease (IBD) with very early onset manifestations (younger than six years of age) is an essential pediatric gastrointestinal disease that encompasses a group of diverse and rare genetic defects. It may be associated with chronicity, premalignant nature, and high morbidity and mortality during childhood. Because of overlapping phenotypes, the definitive diagnosis based on conventional strategies is frequently a challenge. However, many patients with different molecular pathologies are treated with the same therapeutic strategy. In this context, it is essential to define a more reliable method to provide an opportunity for a rapid and accurate diagnosis. Here we report a novel homozygous exonic variant in a patient with an IBD-like lesion in the colon during the infancy period. A 7 months old boy who was born of a consanguineous marriage developed gastrointestinal disorders early in life. After complete diagnostic workups, this case underwent conventional therapy of IBD for five months; but clinical remission was not achieved. We identified a novel homozygous mutation (c.684C>T p. (=)) in exon 7 of IL-12RB1 gene that in silico studies indicated its significance in the splicing process. At the 14th month of age, this case died. Our finding reveals the importance of genetic screening as an early diagnostic tool in the identification of the underlying causes of IBD with very early onset manifestations, particularly infantile (< 2 years of age) IBD. This strategy makes an opportunity in prompt diagnosis and targeted therapy.
    Keywords: Early onset inflammatory bowel disease, genetic, IL-12RB1 deficiency, pediatric
  • Seyed Masoud Jafarpour, Morteza Salimian, Mehran Mohseni*, Hamid Reza Talari, Akbar Aliasgharzadeh, Bagher Farhood, Habiballah Moradi, Hossein Safari Pages 31-38
    Computed tomography (CT) is one of the most important diagnostic X-ray procedures which plays an important role in increasing the patient dose values. The purpose of this clinical study was to evaluate the efficacy of vitamins E and C in lowering down the level of DNA double strand break (DSB) caused by CT scan. Sixty patients for abdomen/pelvic enhanced CT scan were randomly assigned to placebo (control), vitamin C, and vitamin E groups. The patient blood samples were taken before and immediately after the CT scan. Counting the number of DSB was performed using γ-H2AX method as a sensitive biomarker. Immediately after the CT scan, the mean number of DSBs/cell increased in all three groups of control (131%, P < 0.001), vitamin C (103%, P < 0.001), and vitamin E (66%, P < 0.001) compared to their mean before the CT scan. Furthermore, the results showed that vitamin E decreased the mean number of DSBs/cell by 22% in comparison with the control group (P = 0.023), whereas vitamin C had no significant effect on reducing the DSB (<3%, P = 0.741). It is concluded that the administration of vitamin E one hour before the CT scan, significantly decreases DSB levels.
    Keywords: Computed tomography (CT), DNA double strand break (DSB), vitamin C, vitamin E
  • Mohammad Kamran Sarkandi, Ava Behrouzi, Aboulfazl Fateh, Farzam Vaziri, Mehdi Mirsaeidi, Seyed Davar Siadat* Pages 39-48
    Mycobacterium avium complex (MAC) is an ubiquitous acid-fast bacterium. MAC cell wall and membrane release extracellular vesicles (EVs) into different media. The immunogenic effects of EVs isolated from MAC remain unknown. The aim of this study was to determine the EVs effect on macrophage cytokine production. MAC EVs were extracted and purified using differential centrifuges also known as Claassen’s method, with some modifications. After protein analysis of EVs, and scanning electron microscopy (SEM), the EVs were injected into BALB/c mice for in vivo experiments. The concentration of interferon gamma (IFN-γ) and interleukin 10 (IL-10) in the spleen immune cell culture was measured by sandwich ELISA. We showed for the first time, that MAC can naturally produce EVs. The extraction method was technically-feasible, efficient and affordable. The SEM analysis showed that EVs diameter was similar to other studies on mycobacteria, and EVs maintained their spatial characterization. The results of the cytokine assays indicated that EV-treated cells secreted IL-10 (P = 0.034) but not IFN-γ (P = 0.037). Our findings suggest that EVs of M. avium could have anti-inflammatory effects. They can be used as a suppressor or regulator of inflammation via IL-10. The replication of the anti-inflammatory response of MAC EVs by future studies, may indicate a new therapeutic agent for inflammation.
    Keywords: Mycobacterium avium complex, extracellular vesicle, interferon gamma (IFN-γ), interleukin 10 (IL-10)
  • Noah Mahmood, Zaynab Saad Abdulghany*, Israa Mahdi Al, Sudani Pages 49-55
    Tumor initiation cells or cancer stem cell markers ABCG2 and ALDH1 play pivotal roles in invasion, metastasis, and resistance to cytotoxic agents. In this study, we evaluated the expression levels of ALDH1 and ABCG2 in Iraqi patients with colon cancer and/or benign colon tumors. We also investigated the association between the expression levels of these markers and patients clinicopathological features. The expression levels of ALDH1 and ABCG2 in cancer tissues as well as in benign tumor samples were determined by immunohistochemistry using tumor tissues microarray of TNM (Tumor, Node, Metastasis) in 42 patients with colon cancer samples as well as in 18 corresponding benign tumors. Immunohistochemistry showed that ALDH1 and ABCG2 expression levels were increased by 80% and 76%, respectively in colon cancer tissues as compared to 33% and 28% in benign tumor tissues. The expression levels of ALDH1 and ABCG2 were associated with stages. No significant association was found between the expressions levels of these markers and tumor size, gender, patients' age, and lymph node involvement. These results indicate that the expression levels of ALDH1 and ABCG2 were increased in colon cancer tissues compared to benign tumor tissues in Iraqi patients.
    Keywords: colon cancer, ALDH, ABCG2, immunohistochemistry