Crocin synergistically enhances the anti-proliferative activity of 5-FU through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer

Colorectal-cancer (CRC) is the third most common cause of cancer-related-death, and hence there is a need for the identification of novel-agents to improve the efficacy of existing-therapies. There is growing evidence for the anti-tumor-activity of crocin, although its activity and molecular-mechanisms in CRC remains to be elucidated. Here we explored the therapeutic-application of crocin or its combination with 5-Flurouracil in a mouse-model of colitis-associated colon-cancer. The anti-proliferative-activity of crocin was assessed in 2- and 3-dimensional cell-culture-models. The migratory-behaviors were determined, while the expression-levels of several-genes were assessed by qRT-PCR/Western-blotting. We examined the anti-inflammatory properties of crocin by pathological-evaluation and disease-activity-index as well as oxidative/ antioxidant markers: malondialdehyde (MDA) and total-thiols (T-SH) levels and superoxide-dismutase (SOD) and catalase (CAT) activity. Crocin suppressed cell-growth and the invasive-behavior of CRC-cells through modulation of the Wnt-pathway and E-cadherin. Moreover, administration of crocin alone, or in combination with 5-FU dramatically reduced the tumor-number and tumor-size in both distal/mid-colon followed by reduction in disease-activity-index. Crocin also suppressed the colonic-inflammation induced by Dextran-sulfate-sodium and notably recovered the increased-levels of MDA, decreased Thiol-levels and activity of CAT-levels. Crocin was able to ameliorate the severe-inflammation with mucosal-ulcers and high grade-dysplastic-crypts as detected by inflammation-score, Crypt-loss, pathological-changes and histology-scores. We demonstrated an antitumor-activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC

Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease

Funding Information: This study was supported by Mashhad and Isfahan University of Medical Sciences. The authors would like to thank technicians of Sina, Sadi, Ghaem catheterization laboratory and technicians of Isfahan Alzahra genetics laboratory.Peer reviewedPublisher PD

Hookah smoking is strongly associated with diabetes mellitus, metabolic syndrome and obesity: a population-based study

Objectives The adverse effects of cigarette smoking have been widely studied before, whilst the effects of hookah smoking has received less attention, although it is a common habit in the Middle East. Here we have investigated the effects of cigarette and hookah smoking on biochemical characteristics in a representative population sample derived from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study, from Northeastern Iran. Study design A total of 9840 subjects from the MASHAD population study were allocated to five groups; non-smokers (6742), ex-smokers (976), cigarette smokers (864), hookah smokers (1067), concomitant cigarette and hookah smokers (41). Methods Baseline characteristics were recorded in a questionnaire. Biochemical characteristics were measured by routine methods. Data were analyzed using SPSS software and p < 0.05 was considered significant. Results After adjustment for age and sex; the presence of CVD, obesity, metabolic syndrome, DM and dyslipidemia were significantly (p < 0.001) related to smoking status. After multivariate analysis, HDL (p < 0.001), WBC (p < 0.001), MCV (p < 0.05), PLT (p < 0.01) and RDW (p < 0.001), and the presence of CVD (p < 0.01), obesity (p < 0.001), metabolic syndrome (p < 0.05) and DM (p < 0.01) remained significant between cigarette smokers and non-smokers. Between hookah smokers and non-smokers; uric acid (p < 0.001), PLT (p < 0.05) and RDW (p < 0.05), and the presence of obesity (p < 0.01), metabolic syndrome (p < 0.001), diabetes (p < 0.01) and dyslipidemia (p < 0.01) remained significant after logistic regression. Conclusion There was a positive association between hookah smoking and metabolic syndrome, diabetes, obesity and dyslipidemia which was not established in cigarette smoking

Effects of Asphyxia on Colony-forming Ability of Hematopoietic Stem Cell of Cord Blood

Background: Asphyxia is a medical situation resulting from the deprivation of oxygen to a newborn lasting long enough during the birth process to cause physical harm, especially to the brain. Human umbilical cord blood (UCB) is a well-established source of hematopoietic stem/progenitor cells (HSPCs) for allogeneic stem cell transplantation. A low level of O2 in neonates with asphyxia during labor can affect proliferation and differentiation of stem cells in cord blood. Methods: The quality and colony-forming ability of hematopoietic stem cells in the cord blood of neonates with severe asphyxia with Apgar score 3-5or need to cardiac pulmonary resuscitation 5 min after delivery were compared with the group with normal Apgar score. Thereafter, hematopoietic stem cells were isolated, and cells were cultured in an enriched media (MethoCult H4435) special for HSPCs for 7 days to assess the growth and colony formation. Results: Based on the results, there was a significant difference in the number of colonies of RBC (P=0.0016) and WBC precursor (P=0.006), in a plate with 104 cord blood hematopoietic stem cells in newborns exposed to hypoxemia during labor. Conclusion: Umbilical cord blood is valuable for its content of stem cells. Severe hypoxia in the perinatal period does not negatively affect the viability of UCB-derived HSPCs to grow and form colonies. Furthermore, it was found that transient severe asphyxia does not exert negative effects on the banking quality of HSPCs for likely problems in the future

Determining Pro-Oxidant Antioxidant Balance (PAB) and Total Antioxidant Capacity (TAC) in Patients with Schizophrenia

Objective: Schizophrenia is a disease with unknown etiology. There is evidence suggesting that oxidative damage occurs in schizophrenia. Oxidative damage may arouse from imbalance between oxidant and anti-oxidant factors in cellular and tissue environment. Although it may not be the primary cause, it can worsen the disease and may be a reason of poor response to therapy in these patients. The present study aimed at evaluating the pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) in serum of schizophrenia patients. PAB is an assay to determine the pro-oxidant load and antioxidant capacity in a single measurement. Method: In this cross- sectional study, patients with diagnosis of schizophrenia, who referred to a psychiatry university hospital (Ibn-e-Sina Hospital) affiliated to Mashhad University of Medical Sciences, were enrolled. Patients' demographic characteristics and laboratory data were recorded from patients’ files. Serum PAB and TAC were measured using a special PAB assay and commercial kit, respectively. Data were analyzed using SPSS 16. Results: A total of 84 individuals (42 schizophrenia cases and 42 healthy controls) participated in this study. Controls were age and sex-matched with the patients’ group. The mean TAC in the patient and control groups was 0.49±0.04 and 0.51±0.04 nmol/L, respectively (p = 0.16). PAB was higher in patients’ group than in controls (127.36±36.44 vs. 118.93±52.34 HK), however, this difference was not statistically significant (p = 0.09). The change was correlated with the chronicity of the disease. Conclusion: Pro-oxidant antioxidant balance was elevated in serum of patients with schizophrenia. These data suggested the occurrence of oxidative stress during the progression of the disease. Lower antioxidant capacity might suggest that patients with schizophrenia could be more susceptible to oxidative stress damage