An overview of the molecular and clinical significance of the angiopoietin system in leukemia.

The angiogenesis efficacy in solid tumors and hematological malignancies has been identified for more than twenty years. Although the exact role of angiogenesis in leukemia as a common hematological malignancy has not yet been extensively studied, its effect is demonstrated on the initiation and maintenance of a favorable microenvironment for leukemia cell proliferation. The angiopoietin family is a defined molecular mediator for angiogenesis, which contributes to vascular permeability and angiogenesis initiation. They participate in the angiogenesis process by binding to tyrosine kinase receptors (Tie) on endothelial cells. Considering the role of angiogenesis in leukemia development and the crucial effects of the Ang-Tie system in angiogenesis regulation, many studies have focused on the correlation between the Ang-Tie system and leukemia diagnosis, monitoring, and treatment. In this study, we reviewed the Ang-Tie system's potential diagnostic and therapeutic effects in different types of leukemia in the gene expression level analysis approach. The angiopoietin family context-dependent manner prevents us from defining its actual function in leukemia, emphasizing the need for more comprehensive studies.

Comparison of High-Resolution Melting (HRM) Analysis with Direct Sequencing for the Detection of DNMT3A Mutations in AML Patients.

OBJECTIVE: Acute myeloid leukemia (AML) is caused by abnormal gene expression following mutations. Many of the mutations in AML lead to gene instability and poor response to treatment. Among these mutations, DNMT3A mutation is exceedingly important due to its major role in methylation and its effect on the expression of other genes. Aberrant methylation due to DNMT3A mutations that mostly occur in exon 23, affects the overall survival (OS) of patients with AML and myelodysplastic syndromes (MDS) showing the importance of identification of these mutations. According to the association of these mutations with short overall survival and disease progression in AML patients, we aimed to investigate DNMT3A gene exon 23 mutations using HRM. METHODS: Fifty peripheral blood samples were taken from patients with AML. Mononuclear cells were isolated by ficoll method, and DNA was extracted. Then, mutation detection was detected using the HRM method. Efficacy of the HRM method in mutation detection was compared with direct sequencing method as gold standard. RESULTS: Mutations in codon 23 of the DNMT3A gene were detected in 5 patients (10%). All of the detected mutations were missense type. A comparison between direct sequencing and HRM analysis demonstrated full concordance of mutation detection. CONCLUSION: According to the full consistency between the HRM and direct sequencing methods, HRM is suggested to be adopted as an alternative for the common time-consuming methods in detecting the gene mutations.

Rapid Detection of N-RAS Gene Common Mutations in Acute Myeloid Leukemia (AML) Using High Resolution Melting (HRM) Method.

OBJECTIVE: Acute myeloid leukemia is caused by the clonal proliferation of undifferentiated myeloid hematopoietic precursors. AML prognosis is highly involved in the treatment response and is determined by mutations in several genes such as N-RAS. This study aims to identify the distribution of common N-RAS mutations (codons 12, 13, and 61) in AML patients using the HRM method and confirm this method's efficiency for mutation detection by comparing its results with the sequencing data as the Gold standard method. METHODS: Peripheral blood samples were taken from 50 newly diagnosed AML patients. Mononuclear cells were isolated from samples, and DNA was extracted. Then, mutation detection was investigated using the HRM method. Efficacy of the HRM method in mutation detection was determined in comparison with direct sequencing. RESULTS: N-RAS mutations were detected in 7 of the 50 samples (14%). Most of the mutations were found in codon 12 (57.14%), and 28.57% and 14.28% of mutations were in codons 61 and 13, respectively. There was no statistically significant association between patients' demographic data and HRM results. CONCLUSION: According to mutation detection results and the HRM results confirmation with the sequencing method, this method can be introduced as an efficient, low-cost, and fast method for detecting common mutations.

Assessing Moral Skills in General and Post-Graduate Dental Students in the Southeast of Iran: A Cross-Sectional Study

Abstract Objective: To assess the level of moral skills in dental students and residents. Material and Methods: This cross-sectional and descriptive-analytical study was conducted on dental students and residents of Kerman University of Medical Sciences, selected by census sampling. Data collection tools included a demographic information checklist (age, gender, marital status, educational level (before basic sciences, after basic sciences, residency), and moral skills inventory questionnaire. The data were analyzed using a T-test and multiple regression analysis at a confidence level of 95%. Results: The total score of the moral skills questionnaire was about 44 out of 80, and there was no difference between males and females in moral skills (p=0.79). However, there was a significant difference in moral sensitivity between married and single students (p=0.036). Residents gained significantly higher moral integrity scores than students (p=0.046). Conclusion: The study highlights that the level of professional moral skills in Kerman dental students and residents was acceptable. Single students got higher scores in the moral sensitivity domain, although residents got the highest scores in the moral integrity domain. There was no significant correlation between gender and the level of moral skills (AU).

Investigating the expression pattern of the angiopoietin-Tie system in ALL and its correlation with baseline characteristics.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children. Several environmental and genetic factors are known to be involved in its development and progression. The angiopoietin-Tie system is one of the most critical factors in angiogenesis, and its possible role in solid tumors and leukemia has been previously investigated. In this study, we examined the expression of these genes in ALL patients (early pre-B-ALL and pre-B-ALL) and compared them with normal samples. METHODS: Bone marrow samples were collected from 40 patients (aged 0‒19 yr) newly diagnosed with early pre-B-ALL or pre-B-ALL using molecular and flow cytometric tests and from 15 control individuals. For molecular tests, RNA extraction and cDNA synthesis were performed, and Ang1, Ang2, Ang4, Tie1, and Tie2 gene expression was examined by real-time polymerase chain reaction. RESULTS: Ang2, Tie1, and Tie2 gene expression were significantly increased in patients with ALL, whereas Ang1 gene expression was decreased. The Ang4 gene did not show significant expression changes between the two groups. CONCLUSION: Changes in the expression of the Ang-Tie system indicate a possible role of angiogenesis in ALL prognosis. Moreover, such changes can be considered as potential diagnostic biomarkers or therapeutic targets.

IGF family effects on development, stability, and treatment of hematological malignancies.

Multiple factors, including growth factors, are shown to be culprits of cancer outset and persistence. Among growth factors, insulin-like growth factors (IGFs) family are of more importance in the prognosis of blood malignancies. After binding to their corresponding receptor, IGFs initiate PI3K/AKT signaling pathway and increase the translation of intracellular proteins, such as cell division-related proteins. They also stimulate the transcription of cell division-related genes using the Ras-GTP pathway. In addition to organs such as the liver, IGFs are secreted by tumor cells and can cause growth and proliferation of self or tumor cells via autocrine and paracrine methods. Current studies indicate that decreasing the effects of IGF by blocking them, their receptors, or PI3K/AKT pathway using various drugs could help to suppress the division of tumor cells. Here, we delineate the role of the IGF family in hematologic malignancies and their potential mechanisms.

Family history and risk factors for cleft lip and palate patients and their associated anomalies.

BACKGROUND AND AIMS: Several environmental and genetic issues have been suspected as risk factors for oral clefts; and many studies have been conducted in this regard; however, large socioeconomic impacts of cleft lip and or palate (CL/P) justifies the need for further multifactorial researches. Current study aimed to assess parental risk factors for CL/P and its associated malformations. MATERIAL AND METHODS: Hospital records of 187 consecutive syndromic and non-syndromic children with cleft lip and or palate (103 boys and 84 girls) with a mean age of 1.7 (SD 2.2) years and 190 consecutive non-cleft children (103 boys and 87 girls) with a mean age of 2.8 (SD 2.2) years formed this study. Parental risk factors and abnormalities and physical problems and anomalies were evaluated in all subjects. RESULTS: Family history of clefts (OR 7.4; 95% CI), folic acid consumption (OR 7.3; 95% CI) and consanguineous marriage (OR 3.2; 95% CI) were quite strongly associated with increased risk of CL/P. In addition, all congenital abnormalities and physical problems had significantly higher incidence in CL/P patients. CONCLUSIONS: The findings of this study suggest that expecting mothers of consanguineous marriage and families with a history of CL/P should be extra cautious about the occurrence of CL/P.

Orthodontic Treatment of Malocclusion and its Impact on Oral Health-Related Quality of Life.

OBJECTIVES: Malocclusion, though not life-threatening, has vast impact on individual's social interactions and self-esteem. Therefore, the aim of the current study was to assess whether orthodontic treatment of adolescents with malocclusion had any association with their oral health-related quality of life (OHRQoL). METHODS: The subjects for this study were recruited at a state-funded university clinic. Data were collected from 100 participants aged 17 to 21 with moderate to severe malocclusion. Experimental group comprised of 50 subjects who were in the retention phase of their orthodontic treatment and the control group comprised of 50 untreated subjects. The shortened version of the Oral Health Impacts Profile (OHIP-14) as used to assess the subjects' oral health-related impact. T-test, Kruskal-Wallis, and Mann Whitney tests were used to analyze the data and p-value was set at P < 0.05. RESULTS: In general, oral health-related quality of life of all subjects significantly improved after orthodontic treatment. (p<0.001) Subjects with moderate malocclusion showed better improvement than severe malocclusion subjects. (P<0.001). CONCLUSION: This study showed that oral health-related quality of life improves with the treatment of malocclusion.

Effect of occlusal splints on the electromyographic activities of masseter and temporal muscles during maximum clenching.

OBJECTIVES: Despite the broad use of occlusal splints in the treatment of temporomandibular disorders, the efficacy of splints is a source of controversy. In this study, the effectiveness of occlusal splints on the electromyographic activity of the masseter and temporal muscles in healthy individuals was investigated. METHOD AND MATERIALS: An occlusal splint was made for 25 healthy individuals. Surface electromyographic recordings were done during maximum clenching without the splint and immediately after application of the splint. The relative level of activity in the masseter and temporal muscles was quantified by means of activity index. Paired t test and Wilcoxon signed-rank tests were used for data analysis. RESULTS: The mean electromyographic activities of masseter and temporal muscles (in mV/s) were 0.7712 and 1.0488 without the splint and 0.8396 and 0.9276 immediately after application of the splint. There was no significant difference between the electromyographic activities of both muscles before and after insertion of the splints. The activity index increased after application of the occlusal splints. This increase was also insignificant. CONCLUSION: Immediate application of occlusal splints has no significant effect on the activity of masseter and temporal muscles. It could decrease the relative activity of the temporal to the masseter muscle (increasing the activity index).