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Cancer stem cells (CSCs) in cancer progression and therapy
No full textCancer stem cells (CSCs) are self-renewable cell types that are identified in most types of liquid and solid cancers and contributed to tumor onset, expansion, resistance, recurrence, and metastasis after therapy. CSCs are identified from the expression of cell surface markers, which is tumor-type dependent. The transition between CSCs with cancer cells and other non-CSCs occurs in cancers, which is possibly under the control of signals from CSCs and tumor microenvironment (TME), including CSC niche. Cancer-associated fibroblasts are among the most influential cells for promoting both differentiation of CSCs and dedifferentiation of non-CSCs toward attaining a CSC-like phenotype. WNT/β-catenin, transforming growth factor-β, Hedgehog, and Notch are important signals for maintaining self-renewal in CSCs. An effective therapeutic strategy relies on targeting both CSCs and non-CSCs to remove a possible chance of tumor relapse. There are multiple ways to target CSCs, including immunotherapy, hormone therapy, (mi)siRNA delivery, and gene knockout. Such approaches can be designed for suppressing CSC stemness, tumorigenic cues from TME, CSC extrinsic and/or intrinsic signaling, hypoxia or for promoting differentiation in the cells. Because of sharing a range of characteristics to normal stem/progenitor cells, CSCs must be targeted based on their unique markers and their preferential expression of antigens. © 2018 Wiley Periodicals, Inc
Probiotic supplementation improves the cognitive function and the anxiety-like behaviors in the stressed rats
Get PDFObjective(s): Prenatal stresses increase incidence of neurodevelopmental disorders and influence cognitive abilities. Glucocorticoids are released in stress condition as endpoint activation of hypothalamus-pituitary-adrenal (HPA) axis. Evidence indicates a cross-talk between gut microbiota and brain function. This study assesses the effect of probiotic supplementation on behavioral function and HPA axis action in stressed rats. Materials and Methods: The young rats born from dams exposed to noise stress (ST) during third trimester of pregnancy were used. Two groups of stressed animals were received a two-week probiotic supplementation before (pre-ST) and after (post-ST) birth. The time and distance to find hidden platform in Morris water maze were evaluated as spatial memory. Also entry to open arms in elevated plus-maze was considered as anxiety-like behaviors. The serum level of corticosterone was measured as the HPA axis function. Results: While the stressed rats decreased entries to open arms to one third compared to the controls (CON) the probiotic treatment increased the entries by two times. The ST rats required more time and distance to find the platform than did the CON animals. The pre- and post-ST rats significantly restored the impaired behavior almost near the CON ones. While the serum corticosterone concentration increased by 50 in the ST rats it was reduced to almost normal level in the pre- and post-ST rats. Conclusion: Our findings confirmed a link between the gut microbiome and probiotics with the behavioral functions and HPA axis. The probiotic treatment favorably affected the stress-dependent behavioral disorders and the interaction between HPA and gut-brain-microbiota axes. © 2019, Mashhad University of Medical Sciences. All rights reserved
Comparing pregnancy, childbirth, and neonatal outcomes in women with different phenotypes of polycystic ovary syndrome and healthy women: a prospective cohort study
No full textThe aim of this study was to compare pregnancy, childbirth, and neonatal outcomes in women with different phenotypes of polycystic ovary syndrome (PCOS) with healthy women. A prospective cohort study from the beginning to the end of pregnancy for 41 pregnant women with PCOS (case) and 49 healthy pregnant women (control) was completed. Based on the presence or absence of menstrual dysfunction (M), hyperandrogenism (HA), and polycystic ovaries (PCO) on ultrasound, the PCOS (case) group were divided into three phenotypes (HA + PCO (n = 22), M + PCO (n = 9), HA + M+PCO (n = 10). Pre-eclampsia, gestational diabetes, and lower birth weight among newborns were significantly higher in the PCOS case group compared to the control group especially in the phenotype HA + M+PCO (p <.05). High BMI (β = 2.40; p=.03) was the strongest predictor of pre-eclampsia in patients with PCOS. High androgen levels (free androgen index) (β = 13.71, 3.02; p <.05), was the strongest predictor of developing diabetes during pregnancy and reduced birth weight baby, respectively.These results suggest that PCOS, particularly in phenotype HA + M+PCO (p <.05), is a risk factor for adverse pregnancy and neonatal outcomes including gestational diabetes, pre-eclampsia, and reduced weight babies. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group
The effect of resveratrol on neurodegenerative disorders: Possible protective actions against autophagy, apoptosis, inflammation and oxidative stress
No full textThe prevalence of neurodegenerative disorders characterized by the loss of neuronal function is rapidly increasing. The pathogenesis of the majority of these diseases is not entirely clear, but current evidence has shown the possibility that autophagy, apoptosis, inflammation and oxidative stress are involved. The present review summarizes the therapeutic effects of resveratrol on neurodegenerative disorders, based on the especially molecular biology of these diseases. The PubMed, Cochrane, Web of Science and Scopus databases were searched for studies published in English until March 30th, 2019 that contained data for the role of inflammation, oxidative stress, angiogenesis and apoptosis in the neurodegenerative disorders. There are also studies documenting the role of molecular processes in the progression of central nervous system diseases. Based on current evidence, resveratrol has potential properties that may reduce cell damage due to inflammation. This polyphenol affects cellular processes, including autophagy and the apoptosis cascade under stressful conditions. Current evidence supports the beneficial effects of resveratrol on the therapy of neurodegenerative disorders. © 2019 Bentham Science Publishers
The effects of alpha-lipoic acid supplementation on fasting glucose and lipid profiles among patients with stroke: a systematic review and meta-analysis of randomized controlled trials
No full textBackground and objective: Stroke is a devastating condition with long-term comorbidities including metabolic abnormalities. Alpha lipoic acid (ALA), with its antioxidant properties, might improve metabolic status of patients, though current evidence is still inclusive. This systematic review of randomized controlled trials (RCTs) was conducted to summarize the existing evidence regarding the effects of ALA supplementation on fasting glucose and lipid profiles among patients with stroke. Methods: We searched Cochrane Library, EMBASE, MEDLINE, and Web of Science from 1990 until April 5th, 2018. The relevant randomized-controlled articles, based on defined key words, were included in the analyses. Two independent researchers investigated study eligibility, extracted data, and assessed the risk of bias for included studies. Heterogeneity among included studies was tested using Q-test and I2 statistics. Random-effects models were applied to pool the data and standardized mean differences (WMD) were considered as summary effect size. Results: A total of five studies (140 patients in each intervention group) were included in our meta-analysis. The findings showed that ALA supplementation significantly decreased fasting glucose levels (WMD �36.93 mg/dL; 95 CI, �65.58, �8.28; P = 0.01; I2 = 85.0) in patients with stroke. We found no significant effect of ALA supplementation on triglycerides (WMD �7.45 mg/dL; 95 CI, �51.35, 36.45; P = 0.739; I2 = 83.9), total cholesterol (WMD �23.23 mg/dL; 95 CI, �48.07, 1.62; P = 0.067; I2 = 80.5), LDL-cholesterol (WMD �10.46 mg/dL; 95 CI, �21.01, 0.09; P = 0.052; I2 = 47.4) and HDL-cholesterol levels (WMD �3.02 mg/dL; 95 CI, �20.18, 14.14; P = 0.730; I2 = 85.8). Conclusions: This meta-analysis suggested the beneficial impacts of ALA supplementation in improving fasting glucose of patients diagnosed with stroke. © 2019, Springer Nature Switzerland AG
Analyzing food patterns and preferences of urban population of FasA (Phase I of studying the nutritional healthy city in Fasa)
Get PDFBackground: Proper and healthy eating is one of the key steps for developing a healthy population. The risk of disease and mortality decreases with a good nutrition. The access level, quality and choice of food consumed among people are affected by the economic, social, race and cultural status. It means that people with various culture and social system consume various types of food in various amounts. Methods: In a cross-sectional study, 1000 adults living in the Fasa were selected by cluster sampling. Demographic, socioeconomic status, dietary habits, consumption of some important food items such as fruit and vegetables, oils, cereals, dairy, and salt were questioned in a 26 item questionnaire. Results: The results show that there are significant problems in people lifestyle and dietary patterns in Fasa. A significant proportion of population had not regularly consumed breakfast and snack or significant consumption in fruits and vegetables. Hydrogenated vegetable oil and fried oil considerably used, and the most common method to prepare meat products was frying in oil. The refined grains are the major source of energy in people, and whole grains and cereals did not significantly used. Sugar and sweeteners were consumed significantly. Albeit, there were some positive points in the diet of region, including low consumption of carbonated beverages and processed foods, as well as high consumption of dairy products. Conclusion: Significant drawbacks in the dietary pattern of the region exists that need to be planned to improve them to minimize the risk factors of noncommunicable diseases. © Copyright 2019 by Gazi University Medical Facult
Genetic and epigenetic contribution to astrocytic gliomas pathogenesis
Get PDFAstrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas. (Figure presented.). © 2018 International Society for Neurochemistr
Association of EGFR gene mutations exons 18�21 with glioblastoma multiform cancer: A descriptive and cross-sectional study
No full textBackground: Glioblastoma multiforme (GBM), as the most aggressive type of glioma, is grouped as grade IV according to WHO classification. Methods: We included in the present study 20 Iranian patients with GMB, diagnosed between 2013 and 2018. DNA extraction was performed on 10 μm sections from paraffin blocks containing sample tissue. The extracted DNAs were used for amplification by PCR method. PCR products were then subjected to hybridization in order to detect mutations of EGFR. Results: In total, 20 of 20 (100) GBM samples studied had at least one mutation of EGFR. Mutation of G719A in 9 cases, mutations of G719C, G719S and T790M in 16 cases, mutation of E746T751delinesVA in 19 cases, mutations of E746S752delines in 2 cases and mutation of L861Q in 13 cases were observed. However, no significant relationship between EGFR mutations and sex, age, EGFR expression, necrosis, vascular proliferation and atypia was identified. Conclusions: EGFR mutation was found in 100 of patients with GBM. This finding may open avenues for future investigations to explore the effect of combining targeted EGFR therapy with conventional therapies in GMB management. © 201
Reduction of truncated Kit Expression in Men with Abnormal Semen Parameters, Globozoospermia and History of Low or Fertilization Failure
Get PDFObjective: Phospholipase C zeta 1 (PLCζ) is one of the main sperm factor involved in oocyte activation and other factors may assist this factor to induce successful fertilization. Microinjection of recombinant tr-kit, a truncated form of c-kit receptor, into metaphase II-arrested mouse oocytes initiate egg activation. Considering the potential roles of tr-KIT during spermiogenesis and fertilization, we aimed to assess expression of tr-KIT in sperm of men with normal and abnormal parameters and also in infertile men with previous failed fertilization and globozoospermia. Materials and Methods: This experimental study was conducted from September 2015 to July 2016 on 30 normozoospermic and 20 abnormozoospermic samples for experiment one, and also was carried out on 10 globozoospermic men, 10 men with a history low or failed fertilization and 13 fertile men for experiment two. Semen parameters and sperm DNA fragmentation were assessed according to WHO protocol, and TUNEL assay. Sperm tr-KIT was evaluated by flow cytometry, immunostaining and western blot. Results: The results show that tr-KIT mainly was detected in post-acrosomal, equatorial and tail regions. Percentage of tr-KIT-positive spermatozoa in abnormozoospermic men was significantly lower than normozoospermic men. Also significant correlations were observed between sperm tr-KIT with sperm count (r=0.8, P<0.001), motility (r=0.31, P=0.03) and abnormal morphology (r=-0.6, P<0.001). Expression of tr-KIT protein was significantly lower in infertile men with low/ failed fertilization and globozoospermia compared to fertile men. The significant correlation was also observed between tr-KIT protein with fertilization rate (r=-0.46, P=0.04). In addition, significant correlations were observed between sperm DNA fragmentation with fertilization rate (r=-0.56, P=0.019) and tr-KIT protein (r=-0.38, P=0.04). Conclusion: tr-KIT may play a direct or indirect role in fertilization. Therefore, to increase our insight regarding the role of tr-KIT in fertilization further research is warranted. © 2019 Royan Institute (ACECR). All rights reserved
Clinical and metabolic responses to crocin in patients under methadone maintenance treatment: A randomized clinical trial
No full textPatients under methadone maintenance treatment (MMT) programs are susceptible to several complications including metabolic and clinical disorders. This study was designed to determine the effect of crocin supplementation on mental health parameters and metabolic profiles in subjects under MMT. The current randomized, double-blind, placebo-controlled, clinical trial was conducted among 53 patients under MMT to receive either 15 mg/day of crocin (n = 26) or placebo (n = 27) twice a day for 8 weeks. Crocin administration significantly decreased Beck Depression Inventory score (P = 0.01) and Beck Anxiety Inventory score (P = 0.008) compared with the placebo. In addition, crocin administration resulted in a significant reduction in fasting glucose (P = 0.003), insulin levels (P = 0.01), insulin resistance (P = 0.008), triglycerides (P = 0.001), very low-density lipoprotein (P = 0.001), total cholesterol levels (P = 0.03), and a significant increase in insulin sensitivity (.003) compared with the placebo. Additionally, crocin intake was associated with a significant reduction in high-sensitivity C-reactive protein (p <.001) and malondialdehyde (P = 0.001) and a significant rise in total antioxidant capacity levels (P = 0.01) compared with the placebo. The findings of this clinical trial indicate that taking crocin for 8 weeks by patients under MMT had beneficial effects on their mental health and improved their metabolic profiles. © 2019 John Wiley & Sons, Ltd