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Inhibition of MDM2 Using Idasanutlin (RG-7388) enhances the Chemo-sensitivity of B-ALL Cells to Daunorubicin
No full textBackground: Although significant advances have been made in the treatment of cancer, a significant number of patients with acute lymphoblastic leukemia (ALL) show resistance to treatment. Thus, it is necessary to seek novel therapeutic agents to overcome this problem. Studies have indicated that the expression level of mouse double minute 2 (MDM2), a negative regulator of p53, is markedly elevated in patients with refractory or recurrent ALL. Thus, targeting MDM2 using a specific inhibitor, Idasanutlin, can increase the activity of p53. This study evaluated the possible synergistic effect of Idasanutlin and Daunorubicin on the induction of apoptosis in NALM-6 cells.Materials and methods: In this fundamental study, the anti-proliferative effects of Idasanutlin on NALM-6 cells, either alone or in combination with Daunorubicin, were confirmed by MTT(methyl-thiazol-tetrazolium) assay, Annexin/PI apoptosis assay, and cell cycle analysis. Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses were applied to elucidate the molecular mechanisms underlying the anti-leukemic activity of Idasanutlin.Results: Idasanutlin synergistically enhanced Daunorubicin-induced apoptosis and activated caspase-3, thereby activating programmed cell death in a dose-dependent manner (P<0.001). The treatment of NALM-6 cells with Idasanutlin caused cell cycle arrest in the G1 phase by an increase in the expression of p21 (P<0.001). Moreover, a significant increase was detected in the expression of pro-apoptotic genes (P<0.001), as well as a remarkable decrease in the expression of anti-apoptotic (P<0.01) and multidrug resistance1 (MDR1) genes (P<0.01).Conclusions: It seems that Idasanutlin can cooperatively promote daunorubicin-induced apoptosis in NALM-6 cells. These findings open up a new horizon in the application of Idasanutlin in combination with Daunorubicin to overcome drug resistance in patients with ALL
Epidemiological aspect of retinoblastoma in the world: a review of recent advance studies
No full text? AIM: To collect and present updated evidence about epidemiological aspects of retinoblastoma (Rb) in the world.? METHODS: A comprehensive search without the time and language restrictions was conducted in international databases, including MEDLINE, Scopus, Web of Science, and PubMed. The search keywords were "retinoblastoma" OR "retinal Neuroblastoma" OR "retinal glioma" OR "retinoblastoma eye cancer" OR "retinal glioblastoma".? RESULTS: The worldwide incidence of Rb is 1 in 16 000-28 000 live births, but was higher in developing compared to developed countries. Several attempts for improving early detection and treatment had increased the Rb survival rate from 5 to 90 in developed countries over the past decade, but its survival was lower in developing countries (about 40 in low-income countries) and the majority of mortalities occurred in developing countries. The etiology of Rb could be viewed as genetics in the heritable form and environmental and lifestyle factors in the sporadic form. Some environmental risk factors such as in vitro fertilization; insect sprays; father's occupational exposure to oil mists in metal working, and poor living conditions might play a role in the occurrence of the disease. Although ethnicity might affect Rb incidence, sex has no documented effect and the best treatment approaches were now ophthalmic artery chemosurgery and intravitreal chemotherapy.? CONCLUSION: Determining the role of genetics and environmental factors helps to accurately predict the prognosis and identify the mechanism of the disease, which can reduce the risk of tumor development
Effects of choline supplementation in mothers with hypothyroidism on the brain-derived neurotrophic factor gene expression changes in pre-pubertal offspring rats
No full textBackground Thyroid hormones play a vital function in the maturation in the course of mind development. Regarding the well-known effects of choline on brain-derived neurotrophic factor (BDNF), the study examined the effects of choline on hippocampal BDNF gene expression in maternal hypothyroidism rats. Methods and results To induce the hypothyroidism, 6-propyl-2-thiouracil was introduced to the ingesting water from the sixth day of gestation to twenty-first postnatal day (PND). Choline-treatment started twice a day on the first day of gestation until PND 21. On PND28, pups were sacrificed. The expression of BDNF gene was evaluated after the hippocampus was harvested. Our results demonstrated that both male and female pre-pubertal offspring rats' BDNF gene expression was decreased by developmental hypothyroidism. Choline increases the ratio of relative gene expression of BDNF in the hippocampus of males and females in the control/hypothyroidism group, especially in males. Conclusions It can be concluded that maternal choline supplementation on the first day of gestation until PND 21 improves brain development and cognitive function in pre-pubertal offspring rats regarding control/hypothyroidism groups
Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
No full textToday, in the modern world, people are often exposed to electromagnetic waves, which can have undesirable effects on cell components that lead to differentiation and abnormalities in cell proliferation, deoxyribonucleic acid (DNA) damage, chromosomal abnormalities, cancers, and birth defects. This study aimed to investigate the effect of electromagnetic waves on fetal and childhood abnormalities. PubMed, Scopus, Web of Science, ProQuest, Cochrane Library, and Google Scholar were searched on 1 January 2023. The Cochran's Q-test and I (2) statistics were applied to assess heterogeneity, a random-effects model was used to estimate the pooled odds ratio (OR), standardized mean difference (SMD), and mean difference for different outcomes, and a meta-regression method was utilized to investigate the factors affecting heterogeneity between studies. A total of 14 studies were included in the analysis, and the outcomes investigated were: change in gene expression, oxidant parameters, antioxidant parameters, and DNA damage parameters in the umbilical cord blood of the fetus and fetal developmental disorders, cancers, and childhood development disorders. Totally, the events of fetal and childhood abnormalities were more common in parents who have been exposed to EMFs compared to those who have not (SMD and 95 confidence interval CI, 0.25 0.15-0.35; I (2), 91%). Moreover, fetal developmental disorders (OR, 1.34; CI, 1.17-1.52; I (2), 0%); cancer (OR, 1.14; CI, 1.05-1.23; I (2), 60.1%); childhood development disorders (OR, 2.10; CI, 1.00-3.21; I (2), 0%); changes in gene expression (mean difference MD, 1.02; CI, 0.67-1.37; I (2), 93%); oxidant parameters (MD, 0.94; CI, 0.70-1.18; I (2), 61.3%); and DNA damage parameters (MD, 1.01; CI, 0.17-1.86; I (2), 91.6%) in parents who have been exposed to EMFs were more than those in parents who have not. According to meta-regression, publication year has a significant effect on heterogeneity (coefficient: 0.033; 0.009-0.057). Maternal exposure to electromagnetic fields, especially in the first trimester of pregnancy, due to the high level of stem cells and their high sensitivity to this radiation, the biochemical parameters of the umbilical cord blood examined was shown increased oxidative stress reactions, changes in protein gene expression, DNA damage, and increased embryonic abnormalities. In addition, parental exposure to ionizing and non-ionizing radiation can lead to the enhancement of different cell-based cancers and developmental disorders such as speech problems in childhood
Effect of siRNA-mediated silencing of p53R2 gene on sensitivity of T-ALL cellsto Daunorubicin
No full textIntroduction: p53R2 is a p53-inducible protein that, as one of the subunits of ribonucleotide reductase, plays an important role in providing dNTPs for DNA repair. Although p53R2 is associated with cancer progression, its role in T-cell acute lymphoblastic leukemia (T-ALL) cells is unknown. Therefore, in this study, we evaluated the effect of p53R2 silencing on double-stranded DNA breaks, apoptosis and cell cycle of T-ALL cells treated with Daunorubicin. Methods: Transfection was performed using Polyethyleneimine (PEI). Gene expression was measured using real-time PCR and protein expression was evaluated using Western blotting. Cell metabolic activity and IC50 were calculated using MTT assay, formation of double-stranded DNA breaks was checked using immunohistochemistry for & gamma;H2AX, and cell cycle and apoptosis were evaluated using flow cytometry. Results: We found that p53 silencing synergistically inhibited the growth of T-ALL cells by Daunorubicin. p53R2 siRNA in combination with Daunorubicin but not alone increases the rate of DNA double-strand breaks in T-ALL cells. In addition, p53R2 siRNA significantly increased Daunorubicin-induced apoptosis. p53R2 siRNA also caused a non-significant increase in cells in G2 phase. Conclusion: The results of the present study showed that silencing of p53R2 using siRNA can significantly increase the antitumor effects of Daunorubicin on T-ALL cells. Therefore, p53R2 siRNA has the potential to be used as an adjuvant therapy in combination with Daunorubicin in T-ALL
Correction to: High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry
No full textComparing machine learning algorithms to predict COVID‑19 mortality using a dataset including chest computed tomography severity score data
No full textSince the beginning of the COVID-19 pandemic, new and non-invasive digital technologies such as artificial intelligence (AI) had been introduced for mortality prediction of COVID-19 patients. The prognostic performances of the machine learning (ML)-based models for predicting clinical outcomes of COVID-19 patients had been mainly evaluated using demographics, risk factors, clinical manifestations, and laboratory results. There is a lack of information about the prognostic role of imaging manifestations in combination with demographics, clinical manifestations, and laboratory predictors. The purpose of the present study is to develop an efficient ML prognostic model based on a more comprehensive dataset including chest CT severity score (CT-SS). Fifty-five primary features in six main classes were retrospectively reviewed for 6854 suspected cases. The independence test of Chi-square was used to determine the most important features in the mortality prediction of COVID-19 patients. The most relevant predictors were used to train and test ML algorithms. The predictive models were developed using eight ML algorithms including the J48 decision tree (J48), support vector machine (SVM), multi-layer perceptron (MLP), k-nearest neighbourhood (k-NN), Naive Bayes (NB), logistic regression (LR), random forest (RF), and eXtreme gradient boosting (XGBoost). The performances of the predictive models were evaluated using accuracy, precision, sensitivity, specificity, and area under the ROC curve (AUC) metrics. After applying the exclusion criteria, a total of 815 positive RT-PCR patients were the final sample size, where 54.85 of the patients were male and the mean age of the study population was 57.22 +/- 16.76 years. The RF algorithm with an accuracy of 97.2, the sensitivity of 100, a precision of 94.8, specificity of 94.5, F1-score of 97.3, and AUC of 99.9 had the best performance. Other ML algorithms with AUC ranging from 81.2 to 93.9 had also good prediction performances in predicting COVID-19 mortality. Results showed that timely and accurate risk stratification of COVID-19 patients could be performed using ML-based predictive models fed by routine data. The proposed algorithm with the more comprehensive dataset including CT-SS could efficiently predict the mortality of COVID-19 patients. This could lead to promptly targeting high-risk patients on admission, the optimal use of hospital resources, and an increased probability of survival of patients
Correction to: High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry (neurogenetics, (2023), 10.1007/s10048-023-00730-y)
No full textThe published online version of the original article contains a mistake. The authors would like to correct the affiliation of Dr. Nejat Mahdieh as linked above. His work affiliations are listed below. 26Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran 31Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. The authors would like to apologize for any inconvenience caused. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature
Physical Activity and Food Frequency in Postmenopausal Women: A Cross-Sectional Study
No full textBackground & aim: Women spend more than a third of their lives in menopause, and paying attention to their health is one of the most important health issues. The present study was performed to determine the physical activity and food frequency in postmenopausal women. Methods: This cross-sectional study was conducted on 600 postmenopausal women who referred to health centers of Urmia, Iran in 2019. Sampling was performed as multi-stage randomization. To collect data, international physical activity and food frequency questionnaire were used. Results: The mean age of postmenopausal women was 56.64 ± 3.19 years and 93 of them had a body mass index higher than normal. Also, 75 of postmenopausal women had moderate daily physical activity and the average daily physical activity in this group of women was 202.57 ± 135.13 MET. Among the types of physical activities, sports activities had the lowest and working at home had the highest energy consumption. The mean total daily energy intake in postmenopausal women was 3739.80 ± 1251.40 calories, and the consumption of fats, sweets, bread and cereals was more than the standard recommended intake. They had the consumption of dairy products and vegetables less than the need of the body. Conclusion: Postmenopausal women do less daily exercise and use more high-calorie food groups, and their daily energy intake is more than the standard recommended intake. © The Author(s) 2023
Onychomycosis Caused by Rhodotorula mucilaginosa in a Young Immunocompetent Woman in Iran: A Case Report
No full textBackground and Aim: Rhodotorula mucilaginosa (R. mucilaginosa) has emerged as a potential pathogen in immunosuppressed hosts. This fungal agent rarely causes onychomycosis in immunocompetent hosts. In this study, onychomycosis caused by this strain on different fingernails and toenails in an Immunocompetent young adult is reported. Case Report: The patient was an 18-year-old woman with clinical symptoms of powdery, hyperkeratosis brief around erythema in the distal part of a toenail and deformity with a groove on surface of a fingernail who was referred to the Medical Mycology Laboratory of Hazrat Ghaem therapeutic center. After diagnostic procedures, he was treated with oral itraconazole 200 mg/day for 2 months along with topical clotrimazole and sulfacetamide ointment and was cured. The nails responded satisfactorily to the treatment. After two months of stopping the drug, the absence of fungus elements in the clinical samples was confirmed. Diagnosis and identification of the fungus was confirmed by morphological characteristics, culture, and DNA molecular method, and R. mucilaginosa was reported as the etiological agent of onychomycosis. Antifungal drug susceptibility was determined in laboratory using the disk diffusion method according to CLSI guidelines. Conclusion: The isolated species was reported as an unusual species of onychomycosis, which needs to be considered by mycology laboratory and clinical specialists for its sensitivity to ketoconazole, itraconazole, and econazole and its resistance to amphotericin B and nystatin. © 2023 Baqiyatallah University of Medical Sciences. All rights reserved