Anti-tumor effects of crocetin and related molecular targets

Natural products have gained a wide popularity as chemopreventive and anti-cancer agents owing to their multi-mechanistic mode of action, availability and synergism with several conventional chemotherapeutic agents. Crocetin is a carotenoid compound isolated from the stigma of Crocus sativus L. (saffron). Crocetin has shown promising effects as an anti-tumor agent in animal models and cell culture systems. Crocetin retards the growth of cancer cells via inhibiting nucleic acid synthesis, enhancing anti-oxidative system, and inducing apoptosis and differentiation pathways. The present review outlines natural sources of crocetin, and its pharmacokinetic and pharmacological properties relevant to the prevention and treatment of cancer. Also, we discuss molecular targets underlying the putative anti-tumor effects of crocetin. © 2017 Wiley Periodicals, Inc

Short-term in vitro exposure to crocetin promotes apoptosis in human leukemic HL-60 cells via intrinsic pathway

Acute promyelocytic leukemia (APL) is one of the most threatening hematological malignant cancers. Defects in the cell growth and apoptotic pathways are responsible for both the disease pathogenesis and its resistance to therapy. Crocetin, a naturally occurring dietary carotenoid compound, is abundantly found in various plants including Crocus sativus. It has shown chemopreventive and anticancer effects. This study is designed to investigate the apoptogenic potential of crocetin and its underlying mechanism in acute human leukemia HL-60 cells versus normal human polymorph nuclear (PMN) cells. Resazurin assay was used to determine the viability of HL-60 and PMN cells following treatment with crocetin (5-100 µM) and ATRA (10 µM, as positive control) for 24-72 h. Sub-G1 cell population and apoptotic cells were detected by flow cytometry using annexin V and propidium iodide labeling. The levels of genes involved in apoptosis (CASP3, CASP8, CASP9, Bax and Bcl-2) were also determined using real time PCR. The results showed that crocetin concentration-dependently decreased cell viability and increased sub-G1 cell population in HL-60 cells, without significant toxicity toward normal PMN cells. Also, crocetin (100 µM)-treated cells significantly showed apoptosis (15.1 ± 1.3) against 18.8 ± 1.4 in ATRA-treated HL-60 cells during 48 h incubation. In addition, the expressions of CASP3 and CASP9 and Bax/Bcl-2 ratio were significantly increased in HL-60 cells, while CASP8 remained unchanged. It was suggested that crocetin promoted apoptosis in HL-60 cells in concentration-dependent manner through induction of intrinsic pathway. In conclusion, this study suggests that crocetin may be utilized as appropriate alternative for ATRA in APL. © 2018 Polish Pharmaceutical Society. All Rights Reserved

Beneficial effects of Urtica dioica on scopolamine-induced memory impairment in rats: protection against acetylcholinesterase activity and neuronal oxidative damage

This study was conducted to investigate protective effects of Urtica dioica extract on acetylcholinesterase (AChE) activity and the oxidative damage of brain tissues in scopolamine-induced memory impairment model. The rats were treated with (1) saline (control), (2) scopolamine, and (3–5) the plant extract (20, 50, or 100 mg/kg) before scopolamine. The traveled distance and the latency to find the platform in Morris water maze (MWM) by scopolamine-treated group were longer while the time spent in target quadrant was shorter than those of the control. Scopolamine decreased the latency to enter the dark in passive avoidance test. Besides, it also increased AChE activity and malondialdehyde (MDA) concentration in the hippocampal and cortical tissues while decreased thiols content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain (p < 0.01–p <0.001). Treatment by the extract reversed all the effects of scopolamine (p < 0.05–p <0.001). According to the results of present study, the beneficial effects of U. dioica on memory can be attributed to its protective effects on oxidative damage of brain tissue and AChE activity. © 2018 Informa UK Limited, trading as Taylor & Francis Grou

Short-term regular moderate exercise improved male hypothalamic-pituitary-gonadal axis function via the reduction of hypothalamic neurokinin b expression in adult rats

Introduction: In the arcuate nucleus, kisspeptin, neurokinin-B and pro-dynorphin (KNDy) neurons control the function of gonadotropin-releasing hormone (GnRH) neurons. Early investigations indicated that exercise with various intensities affects luteinizing hormone (LH) and testosterone (T) in different ways. Meanwhile the molecular mechanisms underlying its function not yet been fully understood. Accordingly, the present study evaluated the role of alterations in the levels of KNDy mRNA upstream of GnRH neurons in conveying the effects of various short-term exercise intensities on the male hypothermic-pituitary-gonadal (HPG) axis. Methods: Twenty-one adult Wistar rats were randomly divided into 3 groups: control, one-month regular moderate exercise (ME) and one-month regular intensive exercise (IE). In ME (22m/min) and IE (35m/min) groups, the rats were treated 5 days a week for 60min each day. Finally, we assessed serum levels of LH and T using the ELIZA technique and KNDy and Gnrh mRNA expression by the real-time PCR method. Results: The results revealed that in ME group the expression of Nkb was reduced and the expression of Gnrh mRNA and the LH and T serum levels were increased. However, intensive exercise did not change the serum levels of LH and T or the relative expression of kiss1, Nkb, Pdyn and Gnrh genes. Conclusion: The results suggested that monthly moderate exercise improved male reproductive axis function, while intensive exercise did not have an adverse effect on the reproductive axis. These various effects on the male HPG axis may be propagated by the change in hypothalamic Nkb gene expression. © 2021, Iranian Society of Physiology and Pharmacology. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes

Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic, and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5-100 μM) and all-trans retinoic acid (ATRA; 10 μM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML-RAR and HDAC1), and multi-drug resistance (ABCB1 and ABCC1) were determined using quantitative real-time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL-2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration-dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients. © 2017 Wiley Periodicals, Inc

Study of the mechanisms of crocetin-induced differentiation and apoptosis in human acute promyelocytic leukemia cells

Crocetin, the major carotenoid in saffron, exhibits potent anticancer effects. However, the antileukemic effects of crocetin are still unclear, especially in primary acute promyelocytic leukemia (APL) cells. In the current study, the potential antipromyelocytic leukemia activity of crocetin and the underlying molecular mechanisms were investigated. Crocetin (100 µM), like standard anti-APL drugs, all-trans retinoic acid (ATRA, 10 µM) and As2O 3 (arsenic trioxide, 50 µM), significantly inhibited proliferation and induced apoptosis in primary APL cells, as well as NB4 and HL60 cells. The effect was associated with the decreased expressions of prosurvival genes Akt and BCL2, the multidrug resistance (MDR) proteins, ABCB1 and ABCC1 and the inhibition of tyrosyl-DNA phosphodiesterase 1 (TDP1), while the expressions of proapoptotic genes CASP3, CASP9, and BAX/BCL2 ratio were significantly increased. In contrast, crocetin at relatively low concentration (10 µM), like ATRA (1 µM) and As 2O 3 (0.5 µM), induced differentiation of leukemic cells toward granulocytic pattern, and increased the number of differentiated cells expressing CD11b and CD14, while the number of the immature cells expressing CD34 or CD33 was decreased. Furthermore, crocetin suppressed the expression of clinical marker promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) in NB4 and primary APL cells, and reduced the expression of histone deacetylase 1 (HDAC1) in all leukemic cells. The results suggested that crocetin can be considered as a candidate for future preclinical and clinical trials of complementary APL treatment. © 2018 Wiley Periodicals, Inc

Analyzing the Risk of Fire in a Hospital Complex by “Fire Risk Assessment Method for Engineering”(FRAME)

Aims The occurrence of fire in residential buildings, commercial complexes and large and small industries cause physical, environmental and financial damages to many different communities. Fire safety in hospitals is sensitive and it is believed that the society takes the responsibility to care sick people. The goal of this study was to use Fire Risk Assessment Method for Engineering (FRAME) in a hospital complex environment and assess the level of fire risks. Materials & Methods This descriptive study was conducted in Kashan Shahid Beheshti hospital in 2013. The FRAME is designed based on the empirical and scientific knowledge and experiment and have acceptable reliability for assessing the building fire risk. Excel software was used to calculate the risk level and finally fire risk (R) was calculated separately for different units. Findings Calculated Rs were less than 1for health, autoclave, office of nursing and infection control units. R1s were greater than 1 for all units. R2s were less than 1 for office of nursing and infection control units. Conclusion FRAME is an acceptable tool for assessing the risk of fire in buildings and the fire risk is high in Shahid Beheshti Hospital Complex of Kashan and damages can be intolerable in the case of fire

Cancer patients’ satisfaction on nursing care

Objective: to analyze the satisfaction of cancer patients on nursing care. Methods: descriptive quantitative research with 190 patients receiving outpatient chemotherapy in the High Complexity Centre in Oncology, through a questionnaire. Results: 185 respondents (97.4%; 95.0% CI 94.7 to 99.9) said they were always satisfied with the care provided, however, less than a third assessed that charisma (34.2%; 95.0% CI 27.4 to 39.5), respect for their decisions (31.6%; 95.0% CI 24.7 to 37.4) and clear communication (26.3%, CI 20.0 to 31.1) were decisive factors for their satisfaction. Conclusion: the study revealed an excellent level of patient satisfaction on nursing care, although some factors considered by users as decisive for the identification of this feeling have not been significantly identified. This justifies the need for critical reflection, in the professional’s view, that fosters the implementation of changes and to better meet the expectations and needs of the patient