Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy.

Advances in cancer immunotherapy over the last decade have led to the development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells that negatively regulate the immune response include cytotoxic T­lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which have been studied more than similar receptors. Inhibition of these proteins and other immune checkpoints can stimulate the immune system to attack cancer cells, and prevent the tumor from escaping the immune response. However, the administration of anti-PD1 and anti-CTLA4 antibodies has been associated with adverse inflammatory responses similar to autoimmune diseases. The current review discussed the role of the NF-κB pathway as a tumor promoter, and how it can govern inflammatory responses and affect various immune checkpoints. More precise knowledge about the communication between immune checkpoints and NF-κB pathways could increase the effectiveness of immunotherapy and reduce the adverse effects of checkpoint inhibitor therapy.

Thymol, cardamom and Lactobacillus plantarum nanoparticles as a functional candy with high protection against Streptococcus mutans and tooth decay.

Due to the increasing resistance of microorganisms against antibiotics, the use of natural bioactive substances for the prevention of pathogenic bacteria is considered in food products. In this study, thymol, cardamom essential oil, L. plantarum cell-free supernatant (ATCC 14917), and their nanoparticle candies prepared and inhibition activities against S. mutans (ATCC 25175), which is important in causing tooth decay, was investigated. Moisture content, pH, and sensory analyzes of candies measured. Also, SEM and FTIR of treated candy samples were performed. All examined bioactive substances and their nanoparticles showed an inhibitory effect against S. mutans with different minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The prepared candies had pH 5.5 represented a bactericidal effect against S. mutans. SEM and FTIR results approved the antibacterial effects of prepared candies. According to the results, all of the prepared candies significantly decreased S. mutans in saliva compared to the control candy and they are suitable agents for S. mutans growth-inhibiting. Also, cardamom essential oil candy showed the most general acceptance in a sensory analysis by panelists.

The effect of Aromatherapy with Pelargonium graveolens (P. graveolens) on the fatigue and sleep quality of critical care nurses during the Covid-19 pandemic: A randomized controlled trial.

OBJECTIVES: Measures to reduce nurses' fatigue are necessary to improve the patient's care and the nurse's health and well-being. This study investigated the effectiveness of aromatherapy with Pelargonium graveolens (P. graveolens) essential oil on fatigue and sleep quality of nurses working in intensive care units (ICU). METHODS: In this double-blind, randomized, controlled clinical trial, 84 nurses working in the ICU of Covid-19 patients were assigned to two groups of P. graveolens and placebo by the stratified block method. The intervention group inhaled one drop of pure P. graveolens. The placebo group inhaled one drop of pure sunflower oil in three consecutive shifts (morning or evening) and each shift twice for 20 min. Using the Visual Analog Fatigue Scale (VAS-F), fatigue was measured 30 min before the intervention, immediately, and 60 min later. Also, on the morning of the intervention days, sleep quality was assessed with the Verran and Snyder-Halpern (VSH) Sleep Scale. Data analysis was performed using SPSS, version 24. Independent t-tests, Mann-Whitney, Chi-square tests, and MANOVA, were used. RESULTS: The mean score of fatigue immediately and 60 min after aromatherapy in the P. graveolens group was lower than in the control group (P Ë‚ 0.05). There was no significant difference between the mean sleep scores of nurses in the P. graveolens group before and after the intervention (P > 0.05). CONCLUSION: Inhalation aromatherapy with P. graveolens essential oil can reduce nurses' fatigue in the ICU. The findings of this study can make nurses interested in using aromatherapy as a self-care method.

Grain yield and quality of wheat are improved through post-flowering foliar application of zinc and 6- benzylaminopurine under water deficit condition.

Introduction: Zinc (Zn) as an essential micronutrient and cytokinin as phytohormone not only regulate plant growth but also play fundamental roles in plant tolerance against drought stress. Understating the function and the role of cytokinin in combined with an essential micronutrient, Zn, could improve the choice of a sustainable strategy for improvement of plant drought stress. The objective of this field research was to determine the effect of post-flowering foliar application of ZnSO4 and 6-benzylaminopurine (6-BAP) on grain yield and quality of winter wheat under water deficit condition. Methods: Experiments were conducted under filed condition. Drought was imposed by with holding irrigation at the beginning of flowering till the signs of temporary wilting/leaf rolling appeared, after which all plots were irrigated to field capacity. The foliar treatment consisted of (1) foliar application of water, as control treatment; (2) foliar application of 10 g ha-1 6-BAP; (3) Foliar application of 20 g ha-1 6-BAP; (4) Foliar application of 10 g ha-1 6-BAP plus foliar application of 6 kg ha-1 ZnSO4 solution and (5) foliar application of 10 g ha-1 6-BAP plus foliar application of 6 kg ha-1 ZnSO4 solution 2 days before drought imposition. Data were collected on grain and straw yield, yield attributes, harvest index, flag leaf fresh matter and dry matter weight, TaCKX6-D1 expression, phytic acid content in grains, mycorrhiza colonization rate and succinate dehydrogenase (SD) activity. Results: According to ANOVA, the factor 'Zn' significantly affected leaf relative water content (p < 0.001). Relative water content for plants foliar applied with 6-BAP was not statistically significant. Applying Zn increased yield, straw dry weight, and kernel weight relative to plants sprayed with water alone. Increased grain yield due to foliar application of Zn was associated with decrease in cytokinin oxidase/dehydrogenase (TaCKX) and increase in kernel weight. Results showed that the drought stress significantly decreased 1000-grain weight that was accompanied with over-expression of cytokinin oxidase/dehydrogenase (TaCKX). Foliar application of Zn increased the concentration of Zn in grains. The experimental data on the zinc content of grain indicated no significant difference between the 6-BAP at 10 mg L-1 and control treatment. The phytate to Zn molar ratio was significantly affected by foliar applied Zn, but not significantly by applied 6-BAP. In the present study, SD activity of the hyphae of indigenous arbuscular mycorrhizal fungi (IAMF) associated with plant roots was also assayed. Results disclose that SD activity of IAMF was significantly affected by Zn treatments during grain filling stages. Discussion: In summary, both foliar applied Zn and 6-BAP had the significant effects on all measured parameters in winter wheat. However, spike number, harvest index and mycorrhizal colonization rate were neither significantly affected by Zn nor 6- BAP. Foliar application of Zn at 0.6% (6 kg ha-1) and higher 6-BAP (20 mg L-1 m-2) promoted wheat growth and performances under imposed drought stress condition. Plant that only foliar sprayed with water showed higher level of TaCKX6-D1 expression as compared to Zn treated plants, indicating these plants were more affected by imposed drought relative to those plants treated with Zn. The results of this study provides evidence that a combination of Zn and 6-BAP could be an effective in improvement of drought tolerance of wheat and prevents grain yield from further reduction in terms of quality and quantity due to drought stress.

Quantitative CK19 biomarker detection in breast cancer cell lines.

Cytokeratin19 (CK19) was detected as the most related marker for circulating tumor cells, which was assessed in specific cell lines. MCF7, SKBR3, T47D, and MDA-MB-231, and HeLa cell line as negative control were used. CK19 expression was confirmed by using mouse monoclonal anti-human CK19 antibody. CK19 detection in MDA-MB-231 was not observed. CK19 marker expression was compared in T47D, MCF7, and SKBR3 cell lines. T47D and MCF7 belonged to the luminal subtype of breast cancer (BC) that CK19 expression regulated with an ER marker. SKBR3 belonged to the HER2 positive subtype of BC. However, MDA-MB-231 belonged to the claudin-low subtype of BC that lack of CK19 expression strongly is related to negative ER, PR, and HER2. Therefore, there are not only quantitative differences in CK19 expression, but its expression could also link to the other markers of BC that should be considered in the molecular classification of breast carcinoma. Different expression levels related to cell classification could be useful in the prognosis and treatment of cancers with epithelial origins.

The Relationship Between Pre-Transplant Serum Phosphorus Before Kidney Transplantation with Early Graft Dysfunction.

INTRODUCTION: Pre-transplant serum phosphorus level is shown to be associated with some transplant outcomes in patients with chronic kidney disease. However, its association with Delayed graft function (DGF) has an aura of ambiguity. DGF means either the patient needs dialysis during the first week after transplantation or the creatinine level is ≥ 3. This study was aimed to assess the relationship between pre-transplant serum phosphorus levels with DGF. METHODS: A total of 306 patients, who had undergone kidney transplantation in the Montaserieh organ transplantation hospital in Mashhad, Iran, during 2016 to 2019; were enrolled in this study. Demographic data and clinical characteristics of patients including dialysis type and duration, donor type, medications, pre-transplant serum levels of calcium, phosphorus and DGF development were measured. Then, all patients were divided into five groups according to their serum phosphorus: P < 3.5, 3.5 ≤ P < 5.5, 5.5 ≤ P < 7.5, 7.5 ≤ P < 9.5, and P ≥ 9.5 mg/dL. The association with DGF was evaluated by statistical analysis. RESULTS: Patients age ranged from 18.00 to 64.00 years old, with an average of 37.08 ± 10.9. About 55.6% of them were men, and 26.1% came up with DGF. Among patients with DGF, 36.25% were recipients with pre-transplant phosphorus level of 3.5 ≤ P < 5.5 and 50% of 5.5 ≤ P < 7.5. CONCLUSION: Our study suggested that pre-transplant serum phosphorus might be associated with an increased risk of delayed graft function. Further studies are needed to assess, whether adjusting serum phosphorus level before kidney transplantation could reduce delayed graft function or not.

Circulating Tumor Cells Detection in Patients with Early Breast Cancer Using MACS Immunomagnetic Flow Cytometry.

BACKGROUND: Circulating Tumor Cells (CTCs) detection in peripheral blood of epithelial cancer patients is an indicator of the presence of primary tumors and metastasis. The CTC phenotype detection uses epithelial markers in defining, detecting, and isolating CTCs. Circulating cell-separation technologies, with the epithelial origin, can be identified by epithelial biomarkers, with different techniques such as flow cytometry. The purpose of this study was to evaluate the expression of molecular Cytokeratins (CKs), CK7, CK8, CK18, CK19 (Pan-CK) and Epithelial Cell Adhesion Molecule (EpCAM) markers for CTC detection. METHODS: The Magnetic Activated Cell Sorting (MACS) was used to identify CTCs in the blood of patients. Specific antibodies to EpCAM and Pan-CK were used and analyzed by flow cytometry. In this study, 35 blood samples of patients with breast cancer were assessed before any treatment and 35 healthy blood samples as the control were evaluated. RESULTS: Expression of CK markers in the peripheral blood of breast cancer patients was statistically significant with p≤0.05, specifically at stages II-IV, but it was not significant in patients at stage I and healthy controls. Biomarkers expression in the blood of patients and healthy controls was assessed along with the pathologic characteristics of patients. CONCLUSION: CTC assessment by flow cytometry in patients with breast cancer could not only be used for detection but also can be considered as a source of specific and subjective evaluation for monitoring the therapy. Besides, the sensitivity and specificity of CTC detection were shown that could be enhanced by specific CK markers.

Assessment of Cytokeratin-19 Gene Expression in Peripheral Blood of Breast Cancer Patients and Breast Cancer Cell Lines.

Detection of cytokeratin-19 (CK19) expression as an epithelial-specific marker in circulating tumor cells (CTCs) of breast cancer patients can be important for diagnostic purposes. Comparison of CK19 expression in breast cancer cell lines can indicate that expression of this marker is different in various breast cancer cell lines based on their category. Thirty-five breast cancer patients were evaluated for detection of CK19 mRNA in their peripheral blood using CK19-specific primers and a nested reverse transcriptase polymerase chain reaction (RT-PCR) technique. CK19 expression levels were detected in MCF7, T47D, SK-BR-3, and MDA-MB-231 cell lines by semiquantitative RT-PCR and Western blot analyses. Statistical analysis of our data indicates that there is no significant difference between CK19 expression and histopathological parameters and some molecular markers, including Ki-67, HER-2, and P53, but there are statistically significant correlations between estrogen receptor (P = 0.040) and progesterone receptor (P = 0.046) with CK19 expression. CK19 expression was detected in MCF7, T47D, and SK-BR-3 cell lines but not in MDA-MB-231 cell line. More studies are needed to determine the relationship between this marker and other markers in the diagnosis and treatment of breast cancer. On the other hand, the study of different markers using breast cancer cell lines as experimental models of breast cancer could have an impact on improving the health outcomes of patients with breast cancer.