Differentiation-Inducing Activity of the Phyto-polyphenols Epigallocatechin-3-gallate and Kaempferol on NB4 Cells

Background & Objective: The rate of survival in acute promyelocytic leukemia (APL) can dramatically improve, if the patients receive all-trans-retinoic acid (ATRA) treatment. However, this drug's toxicity is a major problem in APL treatment. Previous researches have demonstrated that phyto-polyphenols such as epigallocatechin gallate (EGCG) and kaempferol cause apoptosis in hematopoietic neoplasms, but do not negatively impact healthy cells. The present study compared the differentiation effects of kaempferol and EGCG, as well as ATRA in NB4 leukemia cells during five days. Materials & Methods: Herein, kaempferol and EGCG's differentiation-inducing activity was examined by NBT assay and Real-time PCR in leukemia NB4 cells. Results: EGCG (25 µM) and kaempferol (50 µM) induced the NB4 cells' differentiation, towards a granulocytic pattern similar to ATRA (1 μM). EGCG further suppressed PML/RARα clinical marker's expression compared to kaempferol, it also decreased HDAC1 expression in leukemia NB4 cells. Conclusion: Based on this study, compared to kaempferol, EGCG at low concentrations is preferred for long-term ATRA therapy in APL patients. © 2021, This is an original open-access article distributed under the terms of the Creative Commons Attribution-noncommercial 4.0 International License which permits copy and redistribution of the material just in noncommercial usages with proper citation

A comparative study of anti-leukemic effects of kaempferol and epigallocatechin-3-gallate (EGCG) on human leukemia HL-60 cells

Objective: Acute promyelocytic leukemia (APL) is among the most threatening hematological malignant cancers. Defects in cell growth and apoptotic pathways lead to the pathogenesis of the disease as well as its resistance to therapy; therefore, it is a good model for examining pro-apoptotic agents. The present study compared the molecular mechanism induced by kaempferol and epigallocatechin gallate (EGCG) as well as all-trans retinoic acid (ATRA), in HL-60 leukemia cells during five days. Materials and Methods: Cell viability was determined by resazurin assay following treatment with ATRA (10 ìM), EGCG, and kaempferol (12.5-100 ìM), and apoptosis was detected by the ANX V/PI kit. Moreover, the levels of genes involved in apoptosis (PI3K, AKT, BCL2, BAX, P21, PTEN, CASP3, CASP8, and CASP9) and multi-drug resistance (MDR, ABCB1 and ABCC1) were assessed by using real-time PCR test. Results: Based on the findings, kaempferol decreased cell viability and increased apoptosis in HL60 cells more than EGCG. Apoptosis was induced via extrinsic and intrinsic pathways in HL60 cells by kaempferol and EGCG. In addition, kaempferol and EGCG increased apoptosis and inhibited MDR in a concentration- A nd time-dependent manner. Conclusion: Kaempferol at high concentrations can be taken into consideration for treating patients with APL as compared with EGCG. © 2021 Mashhad University of Medical Sciences. All rights reserved

Inflammatory cytokines and type 2 diabetes

Inflammatory cytokines increase in patients with type 2 diabetes (T2D) and metabolic syndrome. This review focuses on inflammatory cytokines such as C-reactive protein (CRP), tumor necrosis factor (TNF-a), and adiponectin, a cytokine produced by adipose tissue and associated with insulin sensitivity. Despite the major role of cytokines in the development of T2D, in the case of adiponectin still is a matter of debate as the best strategy to change proper inflammatory response. © 2020, Semnan University of Medical Sciences. All rights reserved

Familial adenomatous polyposis: Diagnosis and surveillance strategies: Review article

Familial adenomatous polyposis is characterized by over 100 colorectal adenomas in the colorectum. The disease equally affects both sexes, with an incidence estimated at 1.14025-1.8300. The disease is premature in people with familial adenomatous polyposis. Patients suffering from familial adenomatous polyposis have a range of extra-intestinal diseases such as papillae, gastric, small intestine, and duodenal polyps; cutaneous wounds (lipomas, fibromas, and epidermoid cysts); desmoid tumors; osteomas; nephroderma retinal pigment epithelium, including hepatoblastoma and thyroid cancers; and pancreas, biliary system, and brain cancer. Familial adenomatous polyposis is characterized by >100 polyps in the colon that are often observed on the left side of the colon and rectum. A germline mutation in the adenomatous polyposis coli gene that can be clinically and genetically diagnosed is responsible for this disease. Several methods are available for testing the adenomatous polyposis gene. Whole-gene sequencing of all adenomatous polyposis coli exons and exon-intron boundaries with maximum sensitivity for determining adenomatous polyposis coli mutations is not affordable. Another method, the protein shortening assay, correctly identifies 80 of the mutations in families who show familial adenomatous polyposis and is less expensive than complete gene sequencing. The application of a COX-2 inhibitor for chemical prevention is limited in patients showing familial adenomatous polyposis because of cardiovascular toxicity. Aspirin does not negatively impact cardiovascular diseases and is even used as primary pharmacotherapy in patients who demonstrate cardiovascular risk factors. After 55.7 months of the diagnosis in hereditary CRC carriers, the incidence of cancer can be decreased by a dose of 600 mg/day aspirin for 25 months. After diagnosis, patients should undergo prophylactic proctocolectomy or ileoanal pouch. Undiagnosed patients having a family history of FAP must be referred to a genetic counselor and enrolled in optimal genetic and clinical surveillance programs. Recent advancements in endoscopic technology, e.g. high-resolution endoscopy, doubleballoon endoscopy, and capsule endoscopy have enabled the comprehensive study of the gastrointestinal tract. Despite the limited evidence, more studies on these novel endoscopic technologies may modify the surveillance strategies for FAP patients. © 2020 Tehran University of Medical Sciences. All rights reserved

Inflammation, diet, and type 2 diabetes: a mini-review

Inflammation is a common feature of type 2 diabetes (T2D). Inflammatory cytokines increase in patients with type 2 diabetes, metabolic syndrome, and heart disease. Various types of cells can produce inflammatory cytokines and then release them into the bloodstream, where their complex interactions with target tissues raise a tissue-specific immune response. This review focused on C-reactive protein (CRP), tumor necrosis factor (TNF)-α as an inflammatory cytokine, and adiponectin produced by adipose tissues. Despite the major role of cytokines in the development of T2D, further studies are required to investigate the possible effects of the macronutrient composition of diet on these cytokines. © 2020, © 2020 Taylor & Francis

Serum lysyl oxidase concentration increases in long-standing systemic sclerosis: Can lysyl oxidase change over time?

Objectives: This study aims to investigate the association of serum lysyl oxidase (LOX) levels with systemic sclerosis (SSc), to examine the relationship between LOX and disease onset, and to evaluate the probable effects of hyperlipidemia on the circulating levels of LOX among patients with SSc. Patients and methods: Between May 2017 and November 2018, a total of 39 patients with SSc (2 males, 37 females; mean age: 46.6±12.3 years; range, 18 to 65 years) and 35 healthy controls (4 males, 31 females; mean age: 43.1±14.1 years; range, 18 to 65 years) were included. Serum LOX concentration was measured using the enzyme-linked immunoassay in triplicate. Results: We found higher levels of serum LOX in patients with SSc compared to healthy controls. There was a significant relationship between serum LOX levels and disease onset. Patients with long-standing disease demonstrated increased levels of LOX in the blood compared to the recent-onset group. Hyperlipidemia did not have a significant effect on circulating levels of LOX. There was a significant negative correlation between LOX levels and modified Rodnan Skin Score in the subgroup of patients with skin involvement only and in patients without gastrointestinal involvement. Conclusion: Our study findings show an increased level of LOX protein level in the blood of patients diagnosed with SSc. Hyperlipidemia seems not to affect the concentrations of LOX in the peripheral blood of patients with SSc. © 2022 Turkish League Against Rheumatism. All rights reserved

Influence of Arbuscular Mycorrhizal Fungi and Drought Stress on Some Macro Nutrient Uptake in Three Leek Genotypes with Different Root Morphology

Introduction: Drought stress is one of the main problems in agricultural productions in arid and semiarid regions such as Iran. Lack of water influences on most of plant physiological processes such as photosynthes, cellular development and uptake and transmission of nutrients in plants. Some approaches such as selection of resistance cultivars to drought stress, and selection of dripped irrigation have been applied in order to increase the irrigation efficiency. In recent years, biological approaches such as mycorrhizal symbiosis have been used to alleviate the detrimental effects of drought stress. Mycorrhizal symbioses increase the absorption of nutrients, especially phosphorus, and reduce the adverse effects of environmental stresses. It can also improve the host plant growth and yield. The percentage of mycorrhizal dependency of host plants depends on different environmental factors (such as light intensity, temperature, soil conditions), as well as morphological and physiological characteristics of plants. 1n 2010, a greenhouse pot experiment was conducted at University of Agriculture and Natural Resources Ramin. The effect of mycorrhizal inoculation on root morphology of three leek genotypes and uptake of phosphorous, calcium and potassium in shoot and root were studied. Materials and Methods: The experiment was conducted in a completely randomized design consisting of a 3×3×2 factorial combination. Experimental factors included three levels of soil moisture (40, 60 and 80% of available water in the soil), two mycorrhizal status (with and without fungus Glomus intraradices) and three leek genotypes including: Shadegan (with low root branching, short and thin root length), Esfahan (with abundant root branching and long root length) and Porrum (with low root branching, short and thick root length). The treatments were replicated four times. The soil was autoclaved at 121°C and15 PSI for 15 minutes and gently packed into PVC pots, 200 mm long and 150 mm in diameter. Leek seeds were sterilized with sodium hypochlorite (NaOCl) solution (10%) for 20 min. Two hundred grams of inoculum (spore, hyphae, mycorrhizal clover of root fragments and soil) were placed in deep of plant root. Each pot received 10 cm-3 nutrients solution, free of P weekly. Plants equally watered for one mounth then, drought stresses were applied. Leeks were harvested 12 weeks after planting. Sub-samples of roots were taken for determination of root length were cleared in 10% (w/v) KOH solution and then were stained with trypan blue and root colonization was studied using modified Phillips & Hayman. The colonized root length was determined by binocular and gridline intersect method of Tennant. Phosphorus concentrations were measured by the method of colorimetery with a spectrophotometer. Potassium and calcium concentrations were determined by flame photometer and titration with vercin (Ethylene diamine tetra acetic acid: EDTA), respectively. The statistical analysis was performed using MSTAT-C statistical software and means were compared by Duncan’s multiple range test at the significance level of

Adsorption of sarin and chlorosarin onto the Al12N12 and Al12P12 nanoclusters: DFT and TDDFT calculations

This study provides details of the electronic and optical structures and binding energies of sarin (SF) and chlorosarin (SC) with Al�N and Al�P surfaces of Al12N12 and Al12P12 nanoclusters in the gas phase. The adsorption mechanism of SF and SC on these nanoclusters containing the Al3+ central cation was studied. Optimized geometries and thermodynamic parameters of SF and SC adsorption complexes were calculated. SF and SC are chemisorbed on these nanoclusters because of the formation of P-O···Al bonds. The chemical bond is formed between an oxygen atom of SF and SC and an aluminum atom of fullerene-likes (chemisorption). However, the binding energies of the complexes with the Al12N12 nanocluster are larger than these values for the Al12P12 nanocluster. The interaction enthalpy and Gibbs free energy of all studied systems were found to be negative. We can conclude that SF and SC will be adsorbed preferably on Al12N12 nanocluster. © 2020 John Wiley & Sons, Ltd

The effect of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells in allergic asthma

Introduction: Asthma is becoming a major health problem in many countries. Immune responses in allergic asthma, as the most prevalent asthmatic phenotype, are mediated mostly by a subtype of T lymphocytes referred to as the effector lineage of Type 2 Th cells (Th2). The development of Th2 cells is mainly governed by a zinc finger transcription factor, i.e., GATA-binding protein 3 (GATA3). Allergic asthma is a complex disease, and vitamin D deficiency has been named as a non-genetic risk factor for its development. Vitamin D, a steroid hormone belonging to the family of nuclear receptors, has shown significant immunosuppres-sive effects in previous studies. Material and methods: In this study, given its immunomodulatory properties, we aimed to investigate the effects of different concentrations of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells (PBMCs), including Th2 cells, and compare GATA3 expression levels between PBMCs taken from allergic asthmatic patients and healthy controls. Results: The total sample size was 40 and the quantitative real-time PCR (qPCR) procedure was applied to assess the mRNA expression levels of GATA3 in different groups. Collectively, our results demonstrated that the expression of GATA3 in PBMCs taken from patients with allergic asthma is lower than in that from healthy controls. In addition, in the control group, cells co-cultured with vitamin D had a significantly increased GATA3 expression. However, in the patient group, such an increase was only observed in cells treated with 10-7M-vitamin D. By contrast, incubation with vitamin D at the concentration of 10-6 M slightly decreased the expression of GATA3 among patients. Conclusion: In summary, it is likely that vitamin D should regulate GATA3 gene expression in the PBMCs in a dose-dependent manner. The impacts of this steroid hormone can also differ between the status of health and allergic asthma in either extent or direction. © 2022 PTChP