The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis.

MicroRNAs (miRs) play a crucial role in the leukemogenesis and the prognosis of acute myeloid leukemia (AML). This study investigated the therapeutic effects of resveratrol, gallic acid, and piperine as natural anticancer agents on the HL-60 cell line and their roles in apoptosis. In this experimental study, quantitative analysis of miRs, including miR-17, miR-92b, miR-181a, and miR-222, were performed in 150 newly diagnosed patients with AML by real-time PCR assay. HL-60 cell viability as well as the expression of miRs, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA, were also assessed after transfection with the LNA-miRs and treatment with resveratrol, gallic acid, and piperine. The expression of miR-17 and miR-181a decreased significantly in LNA-anti-miRs. Although HL-60 cell viability decreased in LNA-anti-miR-222, miR-17, and miR-92b, blockade of miR-181a increased the cell viability. Besides, the cell viability increased merely in the piperine-treated group. Compared to untreated cells, miR-17 and miR-92b expression significantly increased in gallic acid- and resveratrol-treated cells. In HL-60 cells treated with resveratrol, gallic acid, and piperine, the expression of miR-181a was also increased significantly. The expression of BAX was also increased in resveratrol and piperine-treated groups. Compared to untreated cells, the expression of c-Kit increased significantly in the piperine-treated group; however, it decreased in the resveratrol-treated group. LNA-anti-miRs may be a promising agent for the treatment of AML. All three compounds used in this study showed anticancer effects, which can exert the desired outcome in patients with AML.

miR-155 and miR-92 levels in ALL, post-transplant aGVHD, and CMV: possible new treatment options.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a malignancy that leads to altered blast cell proliferation, survival, and maturation and eventually to the lethal accumulation of leukemic cells. Recently, dysregulated expression of various micro-RNAs (miRNAs) has been reported in hematologic malignancies, especially ALL. Cytomegalovirus infection can induce ALL in otherwise healthy individuals, so a more detailed evaluation of its role in ALL-endemic areas like Iran is required. METHODS: In this cross-sectional study, 70 newly diagnosed adults with ALL were recruited. The expression level of microRNA-155(miR-155) and microRNA-92(miR-92) was evaluated by real-time SYBR Green PCR. The correlations between the miRNAs mentioned above and the severity of disease, CMV infection, and acute graft vs. host disease after hematopoietic stem cell transplantation (HSCT) were assessed. B cell and T cell ALL distinction in the level of miRNAs was provided. RESULTS: After the statistical analysis, our results indicated a marked increase in the expression of miR-155 and miR-92 in ALL patients vs. healthy controls (*P = 0.002-*P = 0.03, respectively). Also, it was shown that the expression of miR-155 and miR-92 was higher in T cell ALL compared to B cell ALL (P = 0.01-P = 0.004, respectively), CMV seropositivity, and aGVHD. CONCLUSION: Our study suggests that the plasma signature of microRNA expression may act as a powerful marker for diagnosis and prognosis, providing knowledge outside cytogenetics. Elevation of miR-155 in plasma can be a beneficial therapeutic target for ALL patients, with consideration of higher plasma levels of miR-92 and miR-155 in CMV + and post-HSCT aGVHD patients.

Immune checkpoint molecules in prevention and development of asthma.

Allergic asthma is a respiratory disease initiated by type-2 immune responses characterized by secretion of alarmins, interleukin-4 (IL-4), IL-5, and IL-13, eosinophilic inflammation, and airway hyperresponsiveness (AHR). Immune checkpoints (ICPs) are inhibitory or stimulatory molecules expressed on different immune cells, tumor cells, or other cell types that regulate immune system activation and maintain immune homeostasis. Compelling evidence indicates a key role for ICPs in both the progression and prevention of asthma. There is also evidence of asthma development or exacerbation in some cancer patients receiving ICP therapy. The aim of this review is to provide an updated overview of ICPs and their roles in asthma pathogenesis, and to assess their implications as therapeutic targets in asthma.

Should we change our approach to resuscitating victims of femoral fracture? A clinical experience in a busy trauma hospital in Shiraz, Iran.

PURPOSE: Traumatic hemorrhagic shock is a life-threatening event worldwide. Severe brain trauma accompanying femoral fractures can trigger inflammatory responses in the body and increase pre-inflammatory cytokines such as TNF-α, IL-1. The primary treatment in these cases is hydration with crystalloids, which has both benefits and complications. The purpose of this study was to investigate the effects of fluid therapy on the hemodynamics, coagulation profiles, and blood gases in such patients. METHODS: In this cross-sectional study, patients were divided into two groups: femoral fracture group and non-femoral group. The hemodynamic status, coagulation profile, and blood gases of patients in both groups were evaluated upon arrival at the hospital and again 2 h later. Data were analyzed by t-test and ANOVA with repeated data and paired samples t-test. RESULTS: A total of 681 trauma patients (605 men and 76 women) participated in this study, including 69 (86.3%) men and 11 (13.8%) women in femoral fracture group and 536 men (89.2%) and 65 women (10.8%) in non-femoral group. The laboratory parameters were evaluated in response to the equal amount of crystalloid fluid given upon arrival and 2 h later. Blood gases decreased in the fracture group despite fluid therapy (p < 0.003), and the coagulation profile worsened although the change was not statistically significant. CONCLUSION: The treatment of multiple-trauma patients with femoral bone fractures should be more concerned with the need for the infusion of vasopressors such as norepinephrine. If there is evidence of clinical shock, excessive crystalloid infusion (limited to 1 L) should be avoided, and blood and blood products should be started as soon as possible.

Learning operational strategies in surgery training.

INTRODUCTION: Education and training in surgery is in the middle of apprenticeship style of learning especially in operating room with little importance of understanding on how trainees learn. METHODS: This training is one of the most difficult types of training. Medical training and expertise are the specialty of this education system. We can name these complex fields as "Operational Strategies". The strategies are includes of "what to do", "what to think" and "what to create". These strategies are good to test and train higher functions in persons who have professional's positions. RESULTS: Most of educational fields are complex. It means that the training is not limited in an area and includes of theory fields, areas of decision making and areas of handy and practical skills. These fields are the most relevant skills or expertise which individual must be informed of the performance of maintenance and repair or upgrade and make a new system. CONCLUSION:   The operational strategy is a new training strategy for surgery students. It is useful to train surgery students to modify and improve their practices and doing surgeries and treating patients in best conditions.