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Background: Platelet-leukocyte aggregates have been implicated in various infectious and inflammatory diseases. The Interferon-induced transmembrane protein 3 (IFITM3) protein plays a role in eliminating viral infections, but its role in the severity of COVID-19 is not well understood. Objectives: We aimed to investigate the correlation between IFITM3 mRNA expression and platelet-monocyte complex levels with the severity of COVID-19, as well as various inflammatory and coagulation markers. Methods: We conducted a cross-sectional study on 54 COVID-19 patients, classified into severe and mild/moderate subgroups. Demographics and laboratory findings were extracted from patients' medical records. We measured IFITM3 mRNA expression in patients' buffy coats using q-RT-PCR and used flow cytometry with CD61 and CD14 markers to measure platelet-monocyte aggregates. Results: No significant difference was found in IFITM3 mRNA expression levels or platelet-monocyte complexes between severe and mild/moderate groups (P = 0.067 and P = 0.056). Lymphocyte counts were significantly higher in the mild/moderate subgroup (21.7 ± 8.9 vs 16.3 ± 10.9, P = 0.02), while neutrophil counts were significantly higher in severe patients (78.3 ± 12.2 vs 72.3 ± 9.9, P = 0.01). Additionally, levels of CRP and LDH were significantly higher in severe COVID-19 patients (P = 0.01 and P = 0.001, respectively). A strong positive correlation was observed between the hospitalization period and CRP, CRP with neutrophils and LDH, as well as between O2 saturation and lymphocytes (P < 0.001, P = 0.0003, P = 0.002, and P = 0.005, respectively). Conclusions: Our findings suggest that IFITM3 gene expression and platelet-monocyte aggregate levels do not correlate with disease outcomes in COVID-19. However, further investigations with larger sample sizes are needed to better understand the mechanisms involved. Monitoring inflammatory and coagulation markers remains important for managing COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood film morphology in neonates is significantly different from the adults as neonatal erythrocytes show a marked heterogeneity. Moreover, there seem to be a more significant numbers of irregular shaped red blood cells such as stomatocytes, keratocytes, schistocytes, and acantocytes in newborns, particularly in preterm infants. This review study focused on the red blood cell morphology in term and preterm neonates to detect clues to distinguish between the peripheral blood film of newborns under physiological and pathological conditions. Methods: The peripheral blood findings and blood cell counts in preterm and term neonates were studied and compared to each other using available scientific databases and indexing systems such as PubMed and Google Scholar. Results: This approach is a simple, cost-effective, quick, and informative method to distinguish between physiological and pathological conditions in neonates and detect hematological disorders. Conclusions: Peripheral blood film plays a crucial role in diagnosing anemia and blood-related diseases, determining the type of anemia, and identifying specific morphological abnormalities of red cell membrane disorders. [ABSTRACT FROM AUTHOR]

Background: β-thalassemia is an inherited disorder caused by defects in the synthesis of the beta-globin chain. One of the significant clinical complications in β-thalassemia intermedia is iron overload toxicity, which may be attributed to reduced levels of hepcidin. This reduction in hepcidin leads to increased absorption of iron in the intestines, ultimately resulting in iron overload. The objective of this study was to assess the impact of curcumin on the expression of growth differentiating factor-15 (GDF-15) and hepcidin genes in patients with beta-thalassemia intermedia. Methods: This study was designed as a randomized controlled double-blind clinical trial. Prior to and after the intervention period with curcumin, a blood sample of 5 mL was collected from both the placebo and curcumintreated groups for the assessment of hepcidin and growth differentiating factor-15 gene expression. Results: This study revealed a significant reduction in the expression of growth differentiating factor-15 in the curcumin group compared to the placebo group during the 3-month treatment period. Furthermore, curcumin supplementation led to a remarkable 10.1-fold increase in the levels of hepcidin in the curcumin group compared to the placebo group. Conclusions: The results of this study show that curcumin administration increases the mRNA levels of hepcidin in whole blood of thalassemia intermedia patients and supports the idea that curcumin could be a potential treatment to reduce suppression of hepcidin in thalassemias and other iron-loading anemias. [ABSTRACT FROM AUTHOR]

Background: A high number of human breast cancers overexpress the murine double minute (MDM2) gene which blocks the p53 protein which plays an important role in arresting the cell growth. The present study aimed to investigate the efficacy of siRNA specific MDM2 in knocking down MDM2 and its subsequent effects on p53 to exert antiproliferative effects on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Method: In this in vitro study, we used the specific siRNA of the MDM2 gene to knock down the expression of the MDM2 protein in the MCF-7 cell line. The expression of MDM2, BCL2-associated X (BAX), BH3 interacting-domain death agonist (BID), and B cell lymphoma 2 (BCL2) genes was evaluated using the real-time polymerase chain reaction (PCR) technique. The apoptosis level was also assessed using the flow cytometry technique by the Annexin V test. Results: The results showed that the entry of MDM2 siRNA into MCF-7 cells significantly reduced the mRNA expression of MDM2 gene (P-value < 0.05). Besides, the expression of the antiapoptotic gene of BCL2 significantly decreased (P-value < 0.05) in transfected MCF-7 cells, while that of BAX and BID genes increased (P-value < 0.05). Conclusion: Based on the results, MDM2 inhibition is conducive to prevent cancer metastasis by the induction of cancer cell apoptosis. Moreover, it can be considered in cancer therapy along with chemotherapy. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the association between methylation status and expression levels of BTG2, PPP1CA, and PEG3 genes in colon cancer. Background: Aberrant DNA methylation is one of the most important epigenetic modifications in the development of cancer. Evidence indicates that hypermethylation of various tumor suppressor genes could be a potential mechanism of colon tumorigenesis. Methods: The expression levels of BTG2, PPP1CA, and PEG3 genes were evaluated in HT-29/219, HCT116, SW48, SW742, SW480, and LS180 cell lines using quantitative Real-Time PCR. The methylation status of BTG2 and PPP1CA was determined by methylation-specific PCR (MSP) method, and the methylation pattern of PEG3 was evaluated by bisulfite sequencing PCR (BSP). To investigate the effect of methylation on the expression of these genes, all colon cancer cell lines were treated by 5-Azacitidine (5-Aza) and/or Trichostatin A (TSA). Results: The expression levels of BTG2, PPP1CA, and PEG3 were highly heterogeneous and quantitatively correlated to their promoter methylation status in the studied colon cancer cell lines. Treatment by 5-Aza and/or TSA increased the expression of the above-named genes in colon cancer cell lines. Conclusion: Overall, it seems that BTG2, PPP1CA, and PEG3 act as tumor suppressor genes in colon cancer, and methylation is a potential mechanism for their loss of expression. Therefore, these genes may be considered as suitable targets for demethylation approaches and, eventually, colon cancer treatment. Combined treatment by 5-Aza and TSA may be a promising therapeutic strategy for colon cancer treatment. Further studies may contribute to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Acute lymphoblastic leukemia (ALL) is known as a sort of malignancy in the blood lymphoid progenitors, specifically in B and T precursors of the lymphocyte. Autophagy is a protected hemostatic and catabolic process during evolution, through which lysosomes degrade the cytoplasmic components, such as redundant or dysfunctional organelles and misfolded proteins. We conducted the present study to investigate the link between gene expression changes of BECN1, MAP1LC3B, and P62 as the main regulators of remission and response to chemotherapy in ALL patients with minimal/measurable residual disease in ALL. Method: In this case-control study, BECN1, MAP1LC3B, and P62 gene expression were assessed in 30 ALL patients at the diagnosis phase, 18 patients on day 15 of the therapy, and 11 controls employing qRT-PCR. Results: The results revealed that BECN1and MAP1LC3B gene expression levels were significantly lower in ALL patients; whereas, P62 gene expression levels were significantly higher than the controls (P < 0.05). We found that the expression level of the BECN1 and P62 genes increased and decreased respectively in patients on day 15 of the therapy compared with newly diagnosed ALL patients. Nevertheless, neither BECN1 nor P62 genes were significantly different at the rate of 0.73-fold (P > 0.05). Conclusion: Our study demonstrated the relationship between autophagy-related markers, such as BECN1, MAP1LC3B, and P62 with pathogenesis in Iranian children with ALL. We found that BECN1and MAP1LC3B genes significantly decreased in newly diagnosed ALL patients and may play a part in ALL pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Ionizing radiation plays a significant role in cancer treatment. Despite recent advances in radiotherapy approaches, the existence of irradiationresistant cancer cells is still a noteworthy challenge. Therefore, developing novel therapeutic approaches are still warranted in order to increase the sensitivity of tumor cells to radiation. Many types of research rely on the role of mitochondria in radiation protection. Objective: Here, we aimed to target the mitochondria of monocyticleukemia (THP-1) radio-resistant cell line cells by a mitochondrial disrupting peptide, D (KLAKLAK)2, and investigate the synergistic effect of Gamma-irradiation and KLA for tumor cells inhibition in vitro. Material and Methods: In this experimental study, KLA was delivered into THP-1 cells using a Cell-Penetrating Peptide (CPP). The cells were then exposed to gamma-ray radiation both in the presence and absence of KLA conjugated with CPP. The impacts of KLA, ionizing radiation or combination of both were then evaluated on the cell proliferation and apoptosis of THP-1 cells using MTT assay and flow cytometry, respectively. Results: The MTT assay indicated the anti-proliferative effects of combined D (KLAKLAK)2 peptide with ionizing radiation on THP-1cells. Moreover, synergetic effects of KLA and ionizing radiation reduced cell viability and consequently enhanced cell apoptosis. Conclusion: Using KLA peptide in combination with ionizing irradiation increases the anticancer effects of radio-resistant THP-1 cells. Therefore, the combinational therapy of (KLAKLAK)2 and radiation is a promising strategy for cancer treatment the in future. [ABSTRACT FROM AUTHOR]

The induction of fetal haemoglobin (Hb F), due to the sustained clinical effects, is one of the most promising methods for the treatment of β hemoglobinopathies, such as thalassemia major and sickle cell disease (SCD). Inhibition of γ-globin gene silencing, possibly is a suitable strategy to induce HbF expression in these patients. In this study, the possibility of increasing HbF in the CD34+ derived erythroid cells was investigated by BCL11A inhibition using specific small-interfering RNAs (siRNAs). Human peripheral blood-derived hematopoietic stem cells were isolated and differentiated to erythroid cells. Erythroid maturation was investigated using cell morphology parameters and flow cytometry analysis of CD235a expression On day 20, siRNA complementary to BCL11A was transfected to differentiating cells via electroporation. BCL11A expression was evaluated through real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbant assay (ELISA). β actin was used as the reference gene to confirm the relative expression level of BCL11A gene mRNA. 48 hours after transfection, BCL11A siRNA significantly reduced BCL11A mRNA levels and consequently led to 2.0 fold decrease in corresponding protein. On the 28th day, haemoglobin electrophoresis results showed that Hb F levels in transfected erythroid cells increased 3.3-fold when compared with non transfected cells. In this study we showed that BCL11A inhibition in erythroid cells could increase fetal hemoglobin, and this strategy can be the basis for designing a γ globin expressing cellular system to increase Hb F in patients with thalassemia and SCD. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. MicroRNAs (miRNAs) are endogenous small RNA, which can regulate gene expression at the post-transcriptional level. MiRNA profiling has shown a great potential as novel diagnostic and prognostic biomarkers. The present study was performed at the Nemazee Teaching Hospital (Shiraz, Iran) from 2011 to 2013. The aim of this study was to assess the deregulation of miRNAs profiles in DLBL against hyperplasic reactive lymph node as a normal. This could serve as a biomarker for DLBL. The miRCURY LNATM microarray was used on the total RNA, which was extracted from formalin-fixed paraffin-embedded tissue of 24 de novo diffuse large B-cell lymphoma patients and 14 normal lymph nodes. The greatest changes were detected in miR-4284 and miR-4484 level in patient's lymphoma samples. These miRNAs can act as a diagnostic biomarker for DLBL. [ABSTRACT FROM AUTHOR]

Background: Acute renal failure describes as a syndrome by rapid decline in the ability of the kidney to eliminate waste products, regulate acid-base balance, and manage water homeostasis. When this impairment is prolonged and entered chronic phase, erythropoietin secretion by this organ is decreasing and toxic metabolic accumulates and causes hematological changes include decrease of HCT, MCV and RBC and platelet counts. This study evaluates present of anemia and thrombocytopenia in patients with acute and chronic renal failure. Materials and Methods: This study conducted on 132 patients with renal impairment and also 179 healthy individuals as two separated control groups. Initially patients with renal problem were tested and after confirmation of impairment, patients were divided in two groups, acute with less than 3 months and chronic with more than 3 months renal failure, based on duration of the disease. Then complete blood count performed for each patient and finally obtained data were analyzed by SPSS software. Results: Comparison between 96 patients with acute and 36 patients with chronic renal failure revealed that severity of anemia (HCT, Hb and MCV) between these two groups were statistically high in comparison with control groups (P>0.05) but thrombocytopenia in patients with chronic renal failure was statistically different from control and the acute ones (P<0.001). Conclusion: It was recommended that in patients with chronic renal failure, to prevent the risk of bleeding, platelet count should be checked periodically. [ABSTRACT FROM AUTHOR]

Background: Regular blood transfusions to treat the patients with thalassemia major generate antibodies acting against red blood cells antigens. This immune response is called alloimmunity. This study was conducted with the purpose of determining the prevalence of alloantibodies and autoantibody, identifying the type of causative antigen, and recognizing the factors affecting alloimmunization among the patients with thalassemia major receiving blood. Materials and Methods: In this cross-sectional study, 385 patients with thalassemia major participated. After recording their demographic information, serum specimens taken from the patients were screened using pooled cells obtained from Biorad Company. The positive cases were examined to identify antibodies using panel cells obtained from Iranian Blood Transfusion Organization. In this study, SPSS 16 was employed for performing statistical analysis. Results: Of the 385 patients, 69 subjects (17.9%) comprising 221 men and 164 women had alloantibody. In 57 cases, the antibody type was exactly identified. In 21 patients (5.5%) the existence of autoantibody was determined. The mean ages of the participants were within 14.3±7.5 and 13.3±7.9 years old for male and female groups, respectively. 28 patients had splenectomy and age at the onset of blood transfusion ranged from a month after birth to nine years. Conclusion: In these patients, the most significant blood group systems acted by alloantibodies were Rh and Kell. Since the results of this study show 17.9% incidence of alloimmunization in these patients, it is recommended to carry out injected blood compatibility test (cross-match) after antibody screening. [ABSTRACT FROM AUTHOR]

Objective: microRNAs (miRNAs) play bifunctional roles in the initiation and progression of cancer, and recent evidence has confirmed that unusual expression of miRNAs is required for the progress of breast cancer. The regulatory role of aryl hydrocarbon receptor (AhR) and its endogenous ligand, 6-formylindolo[3,2-b]carbazole (FICZ) on the expression of tumor suppressor miRNAs, miR-22, miR-515-5p and miR-124-3p, as well as their association with the estrogen receptor alpha (ERα) were the aims of this study. Materials and Methods: In this experimental study, the expression levels of miR-22, miR-515-5p, miR-124-3p and miR-382-5p in MCF-7 cells were determined using the quantificational real time polymerase chain reaction (qRT-PCR) assay. Results: Our results revealed that miR-22, miR-515-5p, and miR-124-3p expressions were significantly increased in cells transfected with ERα siRNA. Our data also showed that miR-22, miR 515-5p, and miR-124-3p expression levels were significantly increased following FICZ treatment. Here, we found that AhR/ERα cross-talk plays a critical role in the expression of miR-22, miR-515-5p and miR-124-3p in MCF-7 cells. Conclusion: Overall, our data demonstrated that FICZ, as an AhR agonist could induce the expression of tumor suppressor miRNAs, miR-22, miR-515-5p, and miR-124-3p; thus, FICZ might be regarded as a potential therapeutic agent for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: Acute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement in conventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from the Tanacetum parthenium, parthenolide, is a potential anticancer agent that can modulate the expression of miRNAs and induce apoptosis. The objective of this study was to investigate the effect of parthenolide in combination with vincristine and alone on the apoptosis rate and expression of miR-125b-5p, miR-181b-5p, and miR-17-5p in the NALM6 cell line. Materials and Methods: In this experimental study, cell viability and metabolic activity were determined through MTT assay and PI staining. Flow cytometry was applied to evaluate the rate of apoptosis. The expression of miRNAs was assessed using real-time polymerase chain reaction. Bioinformatic analyses, including Cytoscape, RNAhybrid, and signaling pathway analysis were employed to investigate the association of miR-17-5p, miR-181b-5p and miR-125b5p with apoptosis. Further, molecular docking served to validate the modulation of these miRNAs by parthenolide and vincristine treatment. Results: The MTT assay indicated that 7.7 µM of parthenolide decreased the metabolic activity to 50% after 48 hours. PI staining analysis indicated that at concentrations below the half maximal inhibitory concentration, parthenolide caused 50% cell death. Flow cytometric analysis indicated that parthenolide (1.925 µM) in combination with vincristine (1.2 nM) induced apoptosis in 83.2% of the cells. Real-time quantitative reverse transcription polymerase chain reaction (qRTPCR) analysis showed significant changes in the expression levels of miR-17-5p, miR-125b-5p, and miR-181b-5p. Moreover, the combination therapy downregulated the expression of miRNAs significantly. This was consistent with our bioinformatic analysis demonstrating that the studied miRNAs are regulators of apoptosis. Finally, molecular docking validated the modulation of the miRNAs by parthenolide and vincristine. Conclusion: Parthenolide in combination with vincristine triggers apoptosis at a high rate in the NALM6 cell line. Moreover, this combination therapy can decrease the expression of miR-17-5p, miR-181b-5p, and miR-125b-5p. [ABSTRACT FROM AUTHOR]

Introduction: Myeloproliferative neoplasms (MPNs) are divided into BCR-ABL positive Chronic myeloid leukemia (CML) and BCR-ABL negative MPNs including Polycythemia vera (PV), Essential Thrombocythemia (ET) and Primary myelofibrosis (PMF). Evaluation of the Philadelphia chromosome in MPNs is a diagnostic requirement for classic CML., Case Report: In 2020, a 37-year-old woman with negative cytogenetic testing for Janus kinase2 (JAK2), Calreticulin (CALR), myeloproliferative leukemia virus oncogene (MPL), and positive for BCR-ABL1 mutation with reticular fibrosis in bone marrow was diagnosed as CML. Some years ago, the patient had been diagnosed with PMF with evidence of histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD). The BCR-ABL fusion gene was initially evaluated which was negative. Then, Cutaneous squamous cell carcinoma (cSCC) was confirmed by Dermatopathologist with palpable splenomegaly and high white blood cell (WBC) count with basophilia. Finally, BCR-ABL was detected positive by the fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR). In fact, the co-occurrence of PMF with CML was identified., Conclusion: This case study highlighted the importance of some cytogenetic methods in the detection and classification of MPNs. It is recommended that physicians pay more attention to it and be aware of the planning treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Chronic myeloid leukemia (CML) is a progressive myeloproliferative disorder resulting from forming a chimeric BCR-ABL gene. The proteins derived from this gene can affect some genes from various signaling pathways such as PI3K/AKT/Wnt/catenin/JAK/Stat involved in proliferation, differentiation, cell death, and genes related to autophagy. Imatinib is the first-line treatment for CML patients, with durable and proper responses in Iranian children and adult CML patients. Hence, we aimed to evaluate the mRNA expression of some selected key genes from those pathways in patients with CML before and under treatment., Methods: In the case-control study, the mRNA expression of PTEN, LEF1, JAK3, LC3 and p62 genes were measured in 51 CML patients (6 patients before treatment and 45 patients under treatment with imatinib mesylate) and 40 healthy controls using the Real-time PCR method., Results: The mRNA expression of PTEN and P62 were significantly higher in newly diagnosed patients than in controls (P<0.0001 and P = 0.0183, respectively), while the expression of the LC3 gene was significantly lower in the untreated newly diagnosed group than in control subjects (P = 0.0191). The expression level of PTEN, LEF1, JAK3 and P62 genes were significantly decreased in patients under treatment than in the group before treatment (P = 0.0172, P = 0.0002, P = 0.0047 and P = 0.0038, respectively). A positive correlation was seen between the gene expression of P62 and BCR-ABL in the patients under treatment (r 0529, P = 0.016)., Conclusion: Our findings showed that the changes in expression of these genes were related to the patient's treatment. Due to the key role of these genes in proliferation, differentiation and tumor suppression, it is proposed that these genes may be helpful for follow-up of treatment in CML patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ionizing radiation plays a significant role in cancer treatment. Despite recent advances in radiotherapy approaches, the existence of irradiation-resistant cancer cells is still a noteworthy challenge. Therefore, developing novel therapeutic approaches are still warranted in order to increase the sensitivity of tumor cells to radiation. Many types of research rely on the role of mitochondria in radiation protection., Objective: Here, we aimed to target the mitochondria of monocyticleukemia (THP-1) radio-resistant cell line cells by a mitochondrial disrupting peptide, D (KLAKLAK)2, and investigate the synergistic effect of Gamma-irradiation and KLA for tumor cells inhibition in vitro ., Material and Methods: In this experimental study, KLA was delivered into THP-1 cells using a Cell-Penetrating Peptide (CPP).The cells were then exposed to gamma-ray radiation both in the presence and absence of KLA conjugated with CPP. The impacts of KLA, ionizing radiation or combination of both were then evaluated on the cell proliferation and apoptosis of THP-1 cells using MTT assay and flow cytometry, respectively., Results: The MTT assay indicated the anti-proliferative effects of combined D (KLAKLAK) 2 peptide with ionizing radiation on THP-1cells. Moreover, synergetic effects of KLA and ionizing radiation reduced cell viability and consequently enhanced cell apoptosis., Conclusion: Using KLA peptide in combination with ionizing irradiation increases the anticancer effects of radio-resistant THP-1 cells. Therefore, the combinational therapy of (KLAKLAK) 2 and radiation is a promising strategy for cancer treatment the in future., (Copyright: © Journal of Biomedical Physics and Engineering.)