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Acute myeloid leukemia (AML) is a lethal hematologic malignancy with a variable prognosis that is highly dependent on the bone marrow microenvironment. Consequently, a better understanding of the AML microenvironment is crucial for early diagnosis, risk stratification, and personalized therapy. In recent years, the role of bioinformatics as a powerful tool in clarifying the complexities of cancer has become more prominent. Gene expression profile and clinical data of 173 AML patients were downloaded from the TCGA database, and the xCell algorithm was applied to calculate the microenvironment score (MS). Then, the correlation of MS with FAB classification, and CALGB cytogenetic risk category was investigated. Differentially expressed genes (DEGs) were identified, and the correlation analysis of DEGs with patient survival was done using univariate cox. The prognostic value of candidate prognostic DEGs was confirmed based on the GEO database. In the last step, real-time PCR was used to compare the expression of the top three prognostic genes between patients and the control group. During TCGA data analysis, 716 DEGs were identified, and survival analysis results showed that 152 DEGs had survival-related changes. In addition, the prognostic value of 31 candidate prognostic genes was confirmed by GEO data analysis. Finally, the expression analysis of FLVCR2, SMO, and CREB5 genes, the most related genes to patients' survival, was significantly different between patients and control groups. In summary, we identified key microenvironment-related genes that influence the survival of AML patients and may serve as prognostic and therapeutic targets.
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OBJECTIVE: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder resulting from a complex interplay between leukemic cells and supporting factors from their microenvironment. In this context, extracellular vesicles (EVs) have been shown to play an essential role in forming a tumor-protective microenvironment. In this study, we examined the influence of AML-derived EVs on cellular and molecular characterization of bone marrow mesenchymal stromal cells (BM-MSCs), particularly alteration in the expression of genes (IL-6, Gas-6, and Galectin-3) relating to relapse and chemoresistance. METHODS: MSCs were co-cultured with different concentrations of AML-EVs. Our data has been achieved by MTT assay, ROS assay, proliferation assay and apoptosis assay. RT-qPCR was also performed for gene expression analysis. RESULTS: Our results demonstrated that AML-EVs impact the MSCs characterization in a concentration-dependent manner. We revealed higher viability, increased Ki-67 and BCL-2, and lower ROS levels in MSCs treated with a 40 µg/mL dose of EVs. On the other hand, the rate of MSCs apoptosis and BAX expression exposed to a 60 µg/mL dose of EVs were increased compared with the control group. In addition, RT-qPCR results showed that the expression of IL-6, Gas-6, and Galectin-3 was significantly up-regulated in treated MSCs with a 40 µg/mL dose of EVs. CONCLUSION: Because the overexpression of IL-6, Gas-6, and Galectin-3 has contributed to chemoresistance and relapse, our findings suggest that AML-EVs propel MSCs to express these genes, which in turn could guard leukemic cells from chemotherapy-inflicted damages and eventually lead to relapse.
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Vesículas Extracelulares , Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Humanos , Medula Óssea/metabolismo , Galectina 3 , Espécies Reativas de Oxigênio/metabolismo , Interleucina-6/metabolismo , Leucemia Mieloide Aguda/genética , Vesículas Extracelulares/metabolismo , Prognóstico , Proliferação de Células , Células da Medula Óssea/metabolismo , Microambiente TumoralRESUMO
Drug resistance in tuberculosis is exacerbating the threat this disease is posing to human beings. Antibiotics that were once effective against the causative agent, Mycobacterium tuberculosis (Mtb), are now no longer usable against multi- and extensively drug-resistant strains of this pathogen. To address this issue, new drug combinations and novel methods for targeted drug delivery could be of considerable value. In addition, studies have shown that the use of the antidepressant drug fluoxetine, a serotonin reuptake inhibitor, can be useful in the treatment of infectious diseases, including bacterial infections. In this study, an isoniazid and fluoxetine-conjugated multi-walled carbon nanotube nanofluid were designed to increase drug delivery efficiency alongside eliminating drug resistance in vitro. The prepared nanofluid was tested against Mtb. Expression levels of inhA and katG mRNAs were detected by Real-time PCR. ELISA was applied to measure levels of cytokine secretion (TNF-α, and IL-6) from infected macrophages treated with the nano delivery system. The results showed that these nano-drug delivery systems are effective for fluoxetine at far lower doses than for free drugs. Fluoxetine also has an additive effect on the effect of isoniazid, and their concomitant use in the delivery system can have significant effects in treating infection of all clinical strains of Mtb. In addition, it was found that the expression of isoniazid resistance genes, including inhA, katG, and the secretion of cytokines TNFα and IL6 under the influence of this drug delivery system is well regulated. It was shown that the drug conjugation can improve the antibacterial activity of them in all strains and these two drugs have an additive effect on each other both in free and conjugated forms. This nano-drug delivery method combined with host targeted molecules could be a game-changer in the development of a new generation of antibiotics that have high therapeutic efficiencies, low side effects, and the potential to overcome the problem of drug resistance.
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Mycobacterium tuberculosis , Nanopartículas , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/genética , Fluoxetina/farmacologia , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Testes de Sensibilidade Microbiana , Mutação , Nanopartículas/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
BACKGROUND: Mycobacterium fortuitum (M. fortuitum) is a bacterium, which can cause infections in many anatomical regions of the body, including the skin, lymph nodes, and joints. This bacterium, which belongs to a group of bacteria known as nontuberculous mycobacteria, is regarded as an important nosocomial pathogen worldwide owing to its increasing antibiotic resistance. Recently, the antimicrobial effects of carbon nanotubes have been reported in numerous studies. These nanotubes can be very useful in drug delivery; besides, they exhibit unique properties against multidrug-resistant bacterial infections. This study aimed to investigate the antimicrobial effects of carboxyl-functionalized multi-walled carbon nanotubes (MWCNT-COOH) to reduce antibiotic resistance. METHODS: In this study, antibacterial effects of nanofluids containing functionalized MWCNTs at initial concentration of 2 mg/mL and serial dilutions of 54, 28.5, 14.25, 7.12, 3.5 µg/mL, antibiotics alone and combination of nanofluids with antibiotics were investigated. Standard and resistant strains of M. fortuitum were obtained from the microbial bank of the Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran. RESULTS: It was observed that nanofluid containing MWCNT-COOH can exert antimicrobial effects on M. fortuitum and significantly reduce bacterial resistance to antibiotics including kanamycin and streptomycin. In the presence of antibiotics and nanofluids containing MWCNT-COOH at a dose of 28.5 µg/mL, no growth was observed. CONCLUSION: One of the main antimicrobial mechanisms of MWCNT-COOH is penetration into the bacterial cell wall. In this study, by using the nanofluid containing MWCNT-COOH with increased stability, the antibiotic resistance of M. fortuitum was significantly reduced at lower dilutions compared to the antibiotic alone.
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Anti-Infecciosos , Mycobacterium fortuitum , Nanotubos de Carbono , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias , Resistência Microbiana a Medicamentos , Nanotubos de Carbono/químicaRESUMO
Epigenetic alterations could cause leukemia through the activation of normally silent loci or silencing of normally active loci. We herein aimed to compare the expression patterns of a histone modifiers panel consisted of SUV39H1, PRDM16, UHRF2, KDM2B, and KDM3C between acute myeloid leukemia(AML) cells and normal cells and to assess the correlation of these genes with the expression of vital tumor suppressor genes, including p16INK4A and p53. Bone marrow or peripheral blood samples of 50 AML patients at diagnosis and also 18 subjects with a normal hematopoietic system as a control group were obtained after informed consent. Then, qRT-PCR was performed to determine the expression levels of the aforementioned genes. We found a broad alteration in the expression signature of five out of seven studied genes in AML patients as compared with the control group. UHRF2 and p53 were remarkably downregulated in AML patients (P<0.001), while SUV39H1, PRDM16, and KDM3C were significantly overexpressed (P<0.01). Based on the Spearman rank correlation, SUV39H1 and KDM2B negatively regulated both p16INK4A and p53 expression. Taken together, our findings provided preliminary evidence regarding the pervasive mRNA perturbation of histone modifiers and their plausible influences on critical tumor suppressor genes. Future studies in this area would be required to assist in establishing these results in the clinical practice of AML patients.
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Histonas , Leucemia Mieloide Aguda , Metilação de DNA , Genes Supressores de Tumor , Histonas/genética , Histonas/metabolismo , Humanos , Leucemia Mieloide Aguda/genética , RNA Mensageiro/genética , Ubiquitina-Proteína LigasesRESUMO
PURPOSE OF THE STUDY: Acute graft versus host disease (aGVHD) is an immune-mediated reaction that results in impaired immune and body function after allogeneic hematopoietic stem cell transplantation (allo-HSCT). lncRNAs have been discovered as particular T cell regulators, and alloreactive T cells have been known as a critical factor in aGVHD. As a result, we investigated the importance of lnc-MAF4 and IFNG-AS1 expression levels in aGVHD patients versus non-aGVHD patients. MATERIAL AND METHODS: This research included 38 patients with hematological disorders who were undergoing primary allo-HSCT. Human identical siblings or unrelated donors were used to collect stem cell. Samples were taken within days 0, 7, 14, 28, and 52±8 after transplantation. The expression of lncRNA levels was measured using the QRT-PCR technique. And the data were analyzed using GraphPad Prism 6 RESULTS: Our data revealed that LncRNA MAF4 and INFG-AS1 expression levels in aGVHD were not significantly different compared to the non-GVHD group immediately after transplantation, nor at day 7 or 14. However, the aGVHD group showed an overt up-regulation of the two lncRNAs on samples taken at day 28 and 52±8 compared to non-GVHD patients. DISCUSSION: Since the intracellular pathway of these lncRNAs shows a direct relationship with the IFNγ cytokine production resulting in differentiation to TH1 cells and inhibition of differentiation to TH2 cells, they can be, therefore, considered as suitable molecular candidates for the prediction of aGVHD in patients receiving HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , RNA Longo não Codificante , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/genética , Humanos , Interferon gama/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , RNA Longo não Codificante/genéticaRESUMO
In spite of successful initial remission, chemo-resistance and relapse are still concerning points in acute myeloid leukemia (AML) treatment strategies. Multidrug resistance (MDR) appears to be the major contributor of chemo-resistance, arising in some sub-clones of cancers and could be developed in others. The aim of this study was to investigate the role of extracellular vesicles (EVs) derived from AML patients on the transmission of chemo-resistance phenotype. Ultracentrifugation was employed to isolate EVs from healthy controls, new cases, and relapsed AML patients. The EVs size, morphology, and immunophenotype were determined by dynamic light scattering, TEM, and flow cytometry respectively. Bradford assay was performed to measure the protein content of EVs. MTT assay and flow cytometry analysis were also used to determine the viability index, induction of apoptosis, and ROS generation in U937 cells. The expression level of two efflux pumps was assessed using qRT-PCR analysis. Findings of TEM, DLS, and flow cytometry confirmed that EVs had a desirable shape, size, and surface markers. EVs derived from both new cases and relapsed AML patients significantly reduced idarubicin-induced apoptosis in the U937 cells. The analysis of drug efflux pumps gens revealed that EVs over-express MRD1 and MRP1 in the target cells. These findings suggested a novel role of EVs in mediating the acquired chemo-resistance in AML patients by inducing the expression of the drug efflux pumps; however, further investigations will be required to elucidate other underlying mechanisms of resistance that are mediated by EVs.
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The early death, which is more common in acute promyelocytic leukemia (APL) patients rather than other types of acute myelocytic leukemia (AML) highlights the importance of appropriate diagnostic method for early detection of this disease. The low sensitivity of the conventional methods, low tumor burden in some patients, and the need for bone marrow sampling are some of the diagnostic challenges on the way of proper detection of APL. Given these, we aimed to compare the efficacy of extracellular vesicles (EVs), as a diagnostic tool, with the existing methods. RT-PCR, qPCR, and flow cytometry were applied on EVs and their corresponding associated cellular component collected from 18 APL new cases, 23 patients with minimal residual disease (MRD), and NB4 cell line. RT-PCR results were positive in both cellular and vesicular components of all new cases, NB4 cells, and EVs in contrary to MRD cases. Normalized copy numbers (NCN) of PML-RARα were 5100 and 3950 for cell and EVs, respectively (p < 0.05). There was a significant difference in the NCN of PML-RARα between cells and EVs in BM samples. Investigating the effect of storage at room temperature revealed that PML-RARα level was retained near to the baseline level in EVs, but there was a significant reduction in its copy number in the cellular component during 7 days. Taken together, given to the acceptable stability, EVs could be introduced as a non-invasive liquid biopsy that alongside existing methods could remarkably change the paradigm of APL diagnostic approaches.
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Vesículas Extracelulares/genética , Leucemia Promielocítica Aguda/diagnóstico , Proteínas de Fusão Oncogênica/genética , Proteína da Leucemia Promielocítica/genética , Receptor alfa de Ácido Retinoico/genética , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Dosagem de Genes , Humanos , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Neoplasia Residual/genéticaRESUMO
BACKGROUND AND AIMS: As a curative procedure, hematopoietic stemcell transplantation (HSCT) is an approved treatment for many malignant orbenign hematologic and non-hematologic diseases. There are different outcomes of HSCT, as well as several parameters influencing these outcomes. METHODS: We had searched scientific sources like Web ofScience and PubMed with a combination of keywords such as HSCT, engraftment,survival, outcomes, etc. Totally, 80 articles were included. RESULTS: Here we have reviewed the effective factors onmain outcomes of HSCT including engraftment, survival, graft versus hostdisease, and Mobilization. Also, the prediction of hematological reconstitutionand some novel suggestions leading to better outcomes are reviewed. CONCLUSION: The study will be applicable for improvedmanagement of autologous and allogeneic HSCT process to increase the procedureefficiency.
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The involvement of microRNAs in the regulation of hematopoietic stem cells paves the way for their use in the management of autologous HSC transplantation (AHSCT). We aimed to evaluate the predictive value of circulatory microRNAs in extracellular vesicles (EVs) and plasma in platelet and neutrophil engraftment. Circulatory miR-125b, mir-126, miR-150, and miR-155 expression was assessed in isolated EVs and plasma in samples collected from AHSCT candidates. Multivariate analysis, COX models, and ROC assessment were performed to evaluate the predictive values of these microRNAs in platelet and neutrophil engraftment. miR-155 expression following conditioning with other clinical factors such as chemotherapy courses after diagnosis was the most significant predictors of platelet/neutrophil engraftment. A CD34+ cell count ≥ 3.5 × 106/kg combined with miR-155 could be used as an engraftment predictor; however, in cases where the CD34+ cell count was < 3.5 × 106/kg, this parameter lost its predictive value for engraftment and could be replaced by miR-155. The correlation between miR-155 and platelet/neutrophil engraftment even with lower numbers of CD34+ cells suggests the importance of this microRNA in the prediction of AHSCT outcome. Moreover, miR-155 could be utilized in therapeutic approaches to provide a better outcome for patients undergoing AHSCT.
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Plaquetas/metabolismo , Hematopoese/genética , MicroRNAs/genética , Neutrófilos/metabolismo , Biomarcadores , MicroRNA Circulante , Vesículas Extracelulares , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Contagem de Leucócitos , Masculino , Análise Multivariada , Neutrófilos/citologia , Contagem de Plaquetas , Prognóstico , Curva ROC , Transplante AutólogoRESUMO
Several studies show that childhood and adulthood asthma and its symptoms can be modulated through epigenetic modifications. Epigenetic changes are inheritable modifications that can modify the gene expression without changing the DNA sequence. The most common epigenetic alternations consist of DNA methylation and histone modifications. How these changes lead to asthmatic phenotype or promote the asthma features, in particular by immune pathways regulation, is an understudied topic. Since external effects, like exposure to tobacco smoke, air pollution, and drugs, influence both asthma development and the epigenome, elucidating the role of epigenetic changes in asthma is of great importance. This review presents available evidence on the epigenetic process that drives asthma genes and pathways, with a particular focus on DNA methylation, histone methylation, and acetylation. We gathered and assessed studies conducted in this field over the past two decades. Our study examined asthma in different aspects and also shed light on the limitations and the important factors involved in the outcomes of the studies. To date, most of the studies in this area have been carried out on DNA methylation. Therefore, the need for diagnostic and therapeutic applications through this molecular process calls for more research on the histone modifications in this disease.
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Asma/genética , Asma/fisiopatologia , Metilação de DNA/genética , Acetilação , Epigenômica , Expressão Gênica , HumanosRESUMO
By the advent of the effective therapies for many coagulation diseases and hereditary spherocytosis (HS), patient's survival has been improved significantly; however, if patients are diagnosed late or left untreated, both diseases could ominously be life threatening. Concurrent occurring of factor VII (FVII) deficiency and HS is extremely rare and there is no literature report that explain this condition, thus far. In this study, we confronted a 9-year-old female patient diagnosed with HS and enlarged spleen as a result of this blood disorder. Given to her sever signs and symptoms of splenomegaly, she was candidate for emergent splenectomy. However, assessment of coagulation tests revealed a prolonged prothrombin time, suggesting the moderate FVII deficiency. With a multidisciplinary consultation, we decided to performed total splenectomy with prophylaxis administration of totally 6 doses of active recombinant FVII, initiated 1 hour before surgery and followed until 30 hours postoperation. As a result of cautious undertaken in Mofid Children's Hospital, the patient did not experience any hemostatic defect. Patient is now 14-year-old, generally well-being under regular surveillance of FVII deficiency.
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Deficiência do Fator VII/cirurgia , Índice de Gravidade de Doença , Esferocitose Hereditária/cirurgia , Esplenectomia/métodos , Esplenomegalia/cirurgia , Criança , Gerenciamento Clínico , Deficiência do Fator VII/complicações , Deficiência do Fator VII/patologia , Feminino , Humanos , Prognóstico , Esferocitose Hereditária/complicações , Esferocitose Hereditária/patologia , Esplenomegalia/complicações , Esplenomegalia/patologiaRESUMO
BACKGROUND: The recent outbreak by a novel coronavirus originated from Wuhan, China in 2019, and is progressively spreading to other countries. Timely diagnosis of the coronavirus disease 2019 (COVID-19) improves the survival of the patients and also prevents the transmission of the infection. In this study, we reviewed the applicable and available methods for the diagnosis of COVID-19. METHODS: For the review, we systematically searched Web of Science, PubMed, and Iranian articles that were published about COVID-19 diagnostic methods with a combination of the key terms: laboratory, radiological, tests, coronavirus. RESULTS: Although the current gold standard diagnostic test for this virus is real-time reverse-transcriptase polymerase chain reaction (RT-PCR), the occasional false-negative and the low sensitivity of the test should not be underestimated. A chest computed tomography (CT) scan is another diagnostic test for COVID-19, with higher sensitivity but low specificity. A combination of sensitive RT-PCR with a chest CT scan together with the clinical features are highly recommended for the proper diagnosis. Notably, there are some other sensitive and low-cost tests for evaluation of COVID-19 infection, but their validation should be approved. CONCLUSION: Since early and accurate diagnosis of the viral disease could improve the survival rate of the patients, and halt the transmission chain, it is not surprising that tremendous attempts should be made to reduce the limitations of the tests leading to the false-negative results and to find a rapid test for the diagnosis of COVID-19.
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Teste de Ácido Nucleico para COVID-19/normas , COVID-19/diagnóstico , Tomografia Computadorizada por Raios X/normas , Teste Sorológico para COVID-19/normas , Reações Falso-Negativas , Humanos , Pandemias , SARS-CoV-2RESUMO
Acetone is a well-known volatile organic compound that is widely used in different industrial and domestic areas. However, it can have dangerous effects on human life and health. Thus, the realization of sensitive and selective sensors for recognition of acetone is highly important. Among different gas sensors, resistive gas sensors based on nanostructured metal oxide with high surface area, have been widely reported for successful detection of acetone gas, owing to their high sensitivity, fast dynamics, high stability, and low price. Herein, we discuss different aspects of metal oxide-based acetone gas sensors in pristine, composite, doped, and noble metal functionalized forms. Gas sensing mechanisms are also discussed. This review is an informative document for those who are working in the field of gas sensors.
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Citometria de Fluxo , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Androgenic alopecia (AGA), as the most common cause of hair loss, is a chronic process that affects 80% of men and 50% of women throughout life. Existing and approved treatments for this condition are limited, and unfortunately, the length of treatment is long, while its efficacy is not much suitable. Plasma rich in growth factors (PRGF) autologous therapy is based on the delivery of a pool of bioactive molecules impressive for the treatment of AGA.Thirteen patients were included in this study. Our patients were evaluated in two groups: the first group was injected once and the second group was injected thrice, then evaluated for the number and diameter of the hair.Both groups of patients showed hopeful results so that in the first group hairs number and thickness increased by 9-54% and 11-76% respectively (p < .01). For patients who underwent PRGF injection thrice, the increases in hairs number and thickness were remarkably higher with an average of 211 and 221 respectively (p < .001). No adverse effect was reported in any patient.Our results revealed that PRGF platelet concentration using a higher volume of blood compared to previous protocols has higher effectiveness in treating AGA. However, more randomized clinical studies with longer follow up courses as well as larger sample sizes are needed to standardize an optimum protocol for PRGF based treatments.
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Alopecia/terapia , Materiais Biocompatíveis/uso terapêutico , Folículo Piloso/crescimento & desenvolvimento , Cabelo/crescimento & desenvolvimento , Plasma Rico em Plaquetas , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Medicina RegenerativaRESUMO
The morphology of scales from four flank regions in two species of Scorpaeniforme fishes of the family Platycephalidae was studied by applying light and scanning electron microscopy, and the age-dependent variability of scale structures was discussed. The scales of four flank regions from three size classes in both species were ctenoid. The posterior margin of all the ctenoid scales was formed by two rows of cteni, while the three complete rows of cteni were not observed in the examined scales. The cteni of both rows were similar in morphology. Some scale characteristics showed alteration during the fish growth, including the shape of the anterior region of scale in Platycephalus indicus, the presence of lepidonts in Grammoplites suppositus, and the general shape of scale as well as the indices SCL.SCW and JSW.SL in both species. Also, the number of cteni in posterior margin of scales was increased during fish development, while their general morphology did not change significantly. The number of cteni in the scales of small and large fishes in G. suppositus was found to be obviously lower than P. indicus. By considering the function of lepidonts in improving the hydrodynamic efficiency of swimming, it can be assumed that G. suppositus is not probably very active in swimming as P. indicus. As a conclusion, modification in the ornamentations of the posterior region are subject to alteration during the growth of the fish. Besides its developmental changes, some scale characters in the adult forms have taxonomic significance, including the square-shaped scales in P. indicus vs. the oval-shaped scale in G. suppositus; a total of 26-31 radii in the anterior field in P. indicus vs. 11-12 radii in G. suppositus; the presence of many (54-58) cteni in the posterior part in P. indicus vs. a moderate (19-23) cteni in G. suppositus. These characters could be used as additional morphological data to be used for studying systematics and even phylogeny of the flathead fishes.
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Background: Bone marrow hypoxia can promote leukemia progression in human cases of acute myeloid leukemia (AML). In addition, low oxygen tension is able to regulate the expression of different genes involved in malignancy. In this study, we hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF-A) genes were assessed as principal regulators of hypoxia in do novo AML patients. Methods: Peripheral blood and bone marrow samples were collected from 57 AML patients and 17 normal control subjects with informed consent. Expression of HIF1α and VEGF-A was then evaluated using quantitative real-time PCR (Q-Real time PCR) and data were analyzed with SPSS 16. Result: HIF1α and VEGF-A showed overexpression in AML patients compared to normal controls (P <0.0001 and P<0.005, respectively). The expression level of HIF1α was significantly higher in AML-M3 cases versus AML-non M3 cases. Furthermore, there was a positive correlation between HIF1α and VEGF-A ( P <0.0001 and r = 0.497). Conclusion: Adding to the many studies on the role of hypoxia in solid tumors, our data indicate that HIF1a and VEGF-A overexpression also occurs in AML patients. We consider that this is possibly involved in leukemic cell growth and therefore could be a promising target for clinical control.
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Biomarcadores Tumorais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Leucemia Mieloide Aguda/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Lactente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética , Adulto JovemRESUMO
Pre-eclampsia is a common pregnancy disorder syndrome whose molecular mechanism is not clear. Nitric oxide (NO) is a key regulator of placentation. Reduction of NO has previously been associated with endothelial dysfunction in pre-eclamptic women. Therefore, we measured expression and methylation of some placental genes that were involved in NO pathway like named ARG II, PRMT1 and DDAH2 in pre-eclampsia and normal pregnancies in order to determine whether impairment of expression of these genes in the pre-eclamptic placenta could contribute to development of disease. ARG II, PRMT1 expressions as well as DDAH2 expression and methylation, in placentas collected from 59 patients with preeclampsia and 40 normotensive pregnancies were measured using real-time PCR and methylation specific PCR, respectively. The relationship among ARG II, PRMT1 and DDAH2 expressions was analyzed statistically. ARG II expression was increased, PRMT1 expression was not significantly changed. DDAH2 expression was decreased and qualitative methylation patterns were 32/59 and 21/40 in placentas from patients with pre-eclampsia compared with control group, respectively. The alterations in ARG II and DDAH2 expressions in pre-eclampsia patients maybe correlated with decreased eNOS expression. These findings indicate that ARG II and DDAH2 may be involved in pre-eclampsia pathogenesis and could be potential therapeutic targets for this disease.
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Óxido Nítrico/genética , Placenta/patologia , Placentação/genética , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Adulto , Feminino , Humanos , Metilação , Óxido Nítrico Sintase Tipo III/genética , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/patologia , Adulto JovemRESUMO
It has been well documented that preeclampsia (PE) has a common etiological background, but little is known about its linkage at the molecular level.Non- coding RNAs are critical posttranscriptional regulators ofgene expression. This study was performed to determine whether PE is associated with alterations in placental non-coding RNAs expression. MicroRNA (miR)-155-5p and long non-coding RNA (lnc)sONE expression, in placentas collected sequentially from 59 patients with PE and 40 normotensive pregnancies were measured using real-time PCR.The relationship between miR-155-5p and lncsONE expressions was analyzed statistically. miR-155-5p expression was increased (fold change =1.6, P=0.04), while lncsONE expression was not significantly changed (fold change =1.1, P=0.68), in placentas from patients compared with control group.miR-155-5p was upregulated in placentas from patients with PE and may have influenced eNOS expression. These findings indicate that miRNA-155-5p may be involved in PE pathogenesis and could be a potential biomarker for this disease.