Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy.

Acute myeloid leukemia (AML) is a heterogeneous disease developed from the malignant expansion of myeloid precursor cells in the bone marrow and peripheral blood. The implementation of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) has improved outcomes associated with AML, but relapse, along with suboptimal outcomes, is still a common scenario. In the past few years, exploring new therapeutic strategies to optimize treatment outcomes has occurred rapidly. In this regard, natural killer (NK) cell-based immunotherapy has attracted clinical interest due to its critical role in immunosurveillance and their capabilities to target AML blasts. NK cells are cytotoxic innate lymphoid cells that mediate anti-viral and anti-tumor responses by producing pro-inflammatory cytokines and directly inducing cytotoxicity. Although NK cells are well known as short-lived innate immune cells with non-specific responses that have limited their clinical applications, the discovery of cytokine-induced memory-like (CIML) NK cells could overcome these challenges. NK cells pre-activated with the cytokine combination IL-12/15/18 achieved a long-term life span with adaptive immunity characteristics, termed CIML-NK cells. Previous studies documented that using CIML-NK cells in cancer treatment is safe and results in promising outcomes. This review highlights the current application, challenges, and opportunities of CIML-NK cell-based therapy in AML.

Role of the Wnt and GTPase pathways in breast cancer tumorigenesis and treatment.

Breast cancer (BC) is the most frequently diagnosed cancer among women in all the populations of the world. Although the BC mortality rate has declined, resistance to treatment is still a significant challenge for patient survival. Various cellular signaling pathways, such as Wnt and Rho/GTPase have been linked to the development, migration, and metastasis of BC, and also in treatment resistance mechanisms. Some studies have shown an association between two important cellular pathways, Wnt and Rho/GTPase, in cytoskeleton activation and cancer invasion. However, their involvement in BC has received little attention. This review summarizes the Wnt and Rho/GTPases signaling pathway functions, and also the crosstalk between these pathways in the progression, metastasis, and drug resistance mechanisms in BC. Considering the signaling pathways involved in BC tumorigenesis, future studies will need to investigate possible molecular interventions and new opportunities for the development of personalized strategies for BC treatment in order to improve overall outcomes.

Crosstalk between lncRNAs in the apoptotic pathway and therapeutic targets in cancer.

The assertion that a significant portion of the mammalian genome has not been translated and that non-coding RNA accounts for over half of polyadenylate RNA have received much attention. In recent years, increasing evidence proposes non-coding RNAs (ncRNAs) as new regulators of various cellular processes, including cancer progression and nerve damage. Apoptosis is a type of programmed cell death critical for homeostasis and tissue development. Cancer cells often have inhibited apoptotic pathways. It has recently been demonstrated that up/down-regulation of various lncRNAs in certain types of tumors shapes cancer cells' response to apoptotic stimuli. This review discusses the most recent studies on lncRNAs and apoptosis in healthy and cancer cells. In addition, the role of lncRNAs as novel targets for cancer therapy is reviewed here. Finally, since it has been shown that lncRNA expression is associated with specific types of cancer, the potential for using lncRNAs as biomarkers is also discussed.

The effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of hemodialysis-related catheter infection.

Bacterial overgrowth in the inner layer of the catheter as a biofilm is highly encountered in routine medical care, and it may occur in a few days after inserting a catheter as an access in hemodialysis (HD) patients. Catheter-induced bacteremia is often due to the development of biofilms. Locking catheters with antimicrobial agents is an effective way of reducing the risk of catheter-related infection. In a controlled, randomized clinical trial, 64 chronic HD patients (32 men and 32 women with a mean age of 57.5 ± 15.6 years) were divided into case and control groups, with 32 patients in each group. The case group received systemic antibiotic and a lock of catheters with 60% ethanol and the control group received only systemic antibiotic. The results were evaluated after three weeks of treatment. The success rate of clearing infection in group A (29 patients) and group B (18 patients) was 90.6% and 56.2%, respectively (P = 0.002). We conclude that the significant difference in the success rate of clearing catheter infection in HD patients is due to the use of 60% ethanol-lock along with antibiotic therapy, and suggest this for routine use.

Effect of hydroalcoholic extract of Hypericum perforatum on selected traditional and novel biochemical factors of cardiovascular diseases and atherosclerotic lesions in hypercholesterolemic rabbits: A comparison between the extract and lovastatin.

CONTEXT: Evidence suggests that diets with high contents of cholesterol will increase serum lipoproteins and apolipoproteins, thereby increase risk of atherosclerosis. According to literature, some plants show hypolipidemic, hypocholestrolemic, and antiatherosclerotic activities. AIMS: In this study, antiatherosclerotic effect of Hypericum perforatum hydroalcoholic extract on hypercholesterolemic rabbits was compared with that of lovastatin. MATERIALS AND METHODS: Twenty five mature male New Zealand rabbits were randomly divided into five groups of five and were fed for 60 days as follows: Standard diet (GroupI), standard diet and hydroalcoholic extract of Hypericum perforatum (150 mg/kg daily)(GroupII), standard diet, hydroalcoholic extract of Hypericum perforatum (150 mg/ kg daily) and cholesterol (1% of food content) (Group III), standard diet and cholesterol (1% of food content)(GroupIV), and finally standard diet, lovastatin (10 mg/kg), and cholesterol (1% of foodcontent) (GroupV). RESULTS: Hypericum perforatum extract significantly decreased the levels of apolipoprotein B(apoB), apolipoprotein B/apolipoprotein A (apoB/apoA), triglyceride, cholesterol, low density lipoprotein cholesterol, oxidized LDL, malondialdehyde, and C-reactive protein (CRP) as well as atherosclerosis index, and increased high density lipoprotein and apoA in rabbits of Group III compared to the rabbits of Group IV. The effect of Hypericum perforatum extract in decreasing the level of some biochemical factors like apoB, apoB/apoA, and CRP was meaningfully more than that of lovastatin. Histopathological findings confirmed that hydroalcoholic extract of Hypericum perforatum restricted the atherosclerotic lesions. CONCLUSIONS: This study indicates that hydroalcoholic extract of Hypericum perforatum possesses hypolipidemic and anti-atherosclerotic effects and could be beneficial in the management of hyperlipidemia and atherosclerosis.

Levels of lipids and apolipoproteins in three cultures.

OBJECTIVE: A complete lipoprotein profile requires measurement of the major plasma apolipoproteins-apoB and apoA-I-in addition to measurement of the major plasma and lipoprotein lipids. The objective of this study was to demonstrate the additional information that can be acquired by comparing the major plasma lipids and apolipoproteins amongst adult male and female Swedes, Iranians and Americans. METHODS: Data on Iranians were derived from the Isfahan Healthy Heart Program, a prospective community-based sample of 12,103 individuals >20 years of age. Data on Swedes were derived from the AMORIS study, a prospective epidemiological study of 173,629 subjects. Data on Americans were derived from the NHANES III, data bank, which is designed to be representative of the adult American population. Lipids were measured by conventional methods. ApoB and apoA-I were measured by IFCC/WHO standardized methods. RESULTS AND CONCLUSIONS: There is a complex pattern of differences amongst the cultures. There are also important similarities in the differences between the genders. Swedes have the highest levels of LDL-C (3.77 mmol/L), apoB (1.27 g/L) and HDL-C (1.53 mmol/L) but the lowest levels of triglyceride (1.47 mmol/L for the Swedes vs. 1.55 mmol/L and 1.93 mmol/L for the Americans and Iranians, respectively, all p<0.001). Americans have higher levels of LDL-C than Iranians (3.26 mmol/L vs. 3.09 mmol/L, p<0.001) but lower levels of apoB (1.04 g/L vs. 1.14 g/L, p<0.001). The absolute values for both HDL-C and apoA-I are higher in females than males of all three cultures throughout the population distribution. The levels of the atherogenic lipoproteins peak between 30 and 40 in males but continue to rise in females. The apoB/apoA-I ratio is highest in the Swedes (0.92, p<0.001) but similar in the Americans and Iranians (0.81 and 0.80, respectively, p NS). By contrast, the TC/HDL-C ratio is highest in the Iranians, intermediate in the Americans and lowest in the Swedes (4.41 vs. 4.36 vs. 4.22, all p<0.001). These data provide further evidence that complete characterization of lipoproteins requires measurement of apoB and apoA-I as well as lipoprotein lipids and that the changes in plasma lipoproteins over time differ between the genders.

Evaluation of fatty acid content of some Iranian fast foods with emphasis on trans fatty acids.

Although the disadvantages of trans fatty acids (TFAs) are widely mentioned, limited data are available on the TFAs contents of Iranian foods, including fast foods. The aim of this study was to quantify the amounts of common fatty acids in several fast foods in Iran, with specific focus on TFAs. The most commonly consumed fast foods in Iran: sausage, calbas, hamburgers and pizzas, were randomly selected seven times from products available in supermarkets and restaurants. Each time a 10 g sample was drawn and prepared for fatty acid analysis. Total and individual fatty acids were quantified according to standard methods by gas chromatography with 60 meter capillary column and flame ionization detector. The most common saturated fatty acids in Iranian fast foods is stearic acid (C18:0) which ranged from 14.0% to 20.9%. Saturated fatty acid content in calbas was significantly higher than that found in other groups. Trans fatty acids constitute almost 23.6% to 30.6% of total fatty acids of these products. The most common TFA in these fast foods was elaidic acid (C18:1 9t). Total cis unsaturated fatty acid content of tested fast foods varied from 25.3%(in sausage) to 46.8(in calbas) with oleic acid (C18:1 9c) followed by linoleic acid (C18:2) being the most common fatty acids in these products. This study showed higher TFAs contents in commercially available fast foods compared to the amounts recommended by dietary guidelines in Iran. Further studies must assess the effects of these fatty acids on human health.

Effect of ethanolic extract of Juglans regia L. on blood sugar in diabetes-induced rats.

Walnut is one of the medicinal plants used in traditional Iranian medicine as a treatment for diabetes, but little scientific documentation supports its antidiabetic action. This study is designed to evaluate the antidiabetic effect of ethanolic walnut leaf extract. Twenty-four male Wistar rats were divided into four groups: nondiabetic rats, alloxan-induced diabetic rats with no treatment, alloxan-induced diabetic rats treated with ethanolic extracts of Juglans regia (200 mg/kg), and alloxan-induced diabetic rats treated with glibenclamide (0.6 mg/kg). Fasting blood sugar decreased meaningfully in diabetic rats treated with J. regia and diabetic rats treated with glibenclamide. Insulin level increased and glycosylated hemoglobin decreased significantly in diabetic groups receiving either glibenclamide or J. regia compared with the diabetic group with no treatment. The histological study revealed that the size of islets of Langerhans enlarged consequentially as compared with diabetic rats with no treatment. Effects of administering glibenclamide or extract of J. regia on all parameters discussed above showed no difference, and both tended to bring the values to near normal. Our data show the ethanolic extract from leaves of J. regia has a dramatic antidiabetic effect on diabetes-induced rats.