•The effect of rutin on memory was evaluated in rats injected with Aβ.•Rutin increased ERK1, CREB and BDNF gene expression in the hippocampus.•Rutin increased memory retrieval in passive avoidance ...task.•Rutin decreased oxidative stress of Aβ on memory.•Rutin potentially ameliorates the destructive effects of Aβ on memory.
Flavonoids are present in foods such as fruits and vegetables. A relationship between the consumption of flavonoid-rich foods and prevention of human disease including neurodegenerative disorders has been demonstrated. We assessed the effect of rutin (3,3′,4′,5,7-pentahydroxyflavone-3-rhamnoglucoside) on the mitogen-activated protein kinase (MAPK) pathway, memory retrieval and oxidative stress in rats injected with β-amyloid (Aβ), which is implicated to have an important role in Alzheimer's disease (AD). Aβ was injected bilaterally in the deep frontal cortex of rat brain. Next, rutin and saline were injected (i.p.) for 3 weeks. In comparison to the control group, rutin significantly increased extracellular signal-regulated protein kinase 1 (ERK1), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus of rats. Rutin (100mg/kg) significantly increased memory retrieval compared to the control group. Malondialdehyde (MDA) level in the hippocampus of the rutin group was significantly lower than those in the control group. The content of sulfhydryl groups in the rutin group was higher than that in the control group. The findings show a possibility that rutin may have beneficial effects against neurotoxicity of Aβ on memory in rats.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A highly efficient one‐pot synthesis of the 1,2,4,5‐tetrasubstituted imidazoles and 2,4,5,6‐tetrasubstituted pyrimidines through an arylamidine, malononitrile, and carbonyl compound by using Et3N in ...CH3CN at reflux conditions was developed. The nature of the carbonyl compounds were different; when the carbonyl compound was arylglyoxal or aryl aldehyde, 1,2,4,5‐tetrasubstituted imidazole and 2,4,5,6‐tetrasubstituted pyrimidine were achieved respectively.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Nalidixic acid is the first antimicrobial quinolone and today extensively applied in human and veterinary medicine. Recently, it is detected in the surface waters and is on the rise. In this study, ...the renewable adsorbent based on Graphene oxide (i.e., NiZrAl-layered double hydroxide-graphene oxide-chitosan (NiZrAl-LDH-GO-CS NC)), was synthesized and employed effectively for the adsorptive removal of Nalidixic acid (NA). The successful synthesis of the nanocomposite was evaluated using Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray Analysis (EDX), X-ray powder diffraction (XRD), RAMAN spectroscopy, pHZPC and Barrett-Joyner-Halenda (BJH)/ Brunauer–Emmett–Teller (BET) analyses. The NiZrAl-LDH-GO-CS NC presented fast adsorption rates towards NA and maximum adsorption capacity on the basis of the pseudo-second-order (PSO) kinetic model reached 277.79 mg g−1, much higher than those reported by different nano-based adsorbents. The adsorption process was examined using the central composite design (CCD), adaptive network-based fuzzy inference system (ANFIS), and general regression neural network (GRNN) under various operational conditions of adsorbent dose, initial NA concentration, pH, temperature, and time. The comparison of the models revealed that ANFIS model outperformed compared to the others, with R2 = 0.9997, MSE = 0.0004, RMSE = 0.0082, and MAE = 0.0068, demonstrating that ANFIS is a powerful methodology for modeling NA adsorption by NiZrAl-LDH-GO-CS nanocomposite. Moreover, to express the most applicable conditions, RSM-GA and RSM-DFA based optimization is implemented and verified in practice (more than %92 NA removal is achieved). Further thermodynamic and kinetic assessments both signify the chemisorption mechanisms in this adsorption system. To sum up, LDH-GO-CS as a renewable adsorbent, will possibly have noteworthy effects on pharmaceutical wastewater remediation and can be considered for advanced researches as an efficient reagent for practicable remediation techniques.
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•A cost-effective LDH/GO/CS nanocomposite were synthesized for NA removal.•ANFIS was found to be the best model among RSM and GRNN techniques.•The accuracy of Advanced Neural Network for modeling was checked.•Isotherm, thermodynamic, kinetic, and reuse cycles were investigated.•Error function analysis were applied to compare models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Endoplasmic reticulum (ER) stress is involved in the development of glucose homeostasis impairment. When ER stress occurs, the unfolded protein response (UPR) is activated to cope with it. One of the ...UPR components is WFS1 (Wolfram syndrome 1), which plays important roles in ER homeostasis and pancreatic islets glucose-stimulated insulin secretion (GSIS). Accordingly and considering that feeding high-fat food has a major contribution in metabolic disorders, this study aimed to investigate the possible involvement of pancreatic ER stress in glucose metabolism impairment induced by feeding high-fat diet (HFD) in male rats. After weaning, the rats were divided into six groups, and fed on normal diet and HFD for 20 weeks, then 4-phenyl butyric acid (4-PBA, an ER stress inhibitor) was administered. Subsequently, in all groups, after performing glucose tolerance test, the animals were dissected and their pancreases were removed to extract ER, islets isolation and assessment of GSIS. Moreover, the pancreatic ER stress binding of immunoglobulin protein (BIP) and enhancer-binding protein homologous protein (CHOP) and oxidative stress malondialdehyde (MDA), glutathione (GSH) and catalase biomarkers as well as WFS1 expression level were evaluated. HFD decreased pancreatic WFS1 protein and GSH levels, and enhanced pancreatic catalase activity, MDA content, BIP and CHOP protein and mRNA levels as well as Wfs1 mRNA amount. Accordingly, it increased BIP, CHOP and WFS1 protein levels in the extracted ER of pancreas. In addition, the HFD caused glucose intolerance, and decreased the islets' GSIS and insulin content. However, 4-PBA administration restored the alterations. It seems that, HFD consumption through inducing pancreatic ER stress, altered WFS1 expression levels, reduced the islets' GSIS and insulin content and finally impaired glucose homeostasis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
OBJECTIVES
Coronary artery disease is becoming a major health concern in the young population. Male and female patients may experience different journeys after coronary artery disease ...events. We aimed to evaluate risk factors and compare outcomes between young male and female patients undergoing coronary artery bypass graft surgery (CABG).
METHODS
In this registry-based large sample size study, patients undergoing isolated CABG at a young age (premature isolated CABG) between 2007 and 2016 were included and followed up until 2020. Premature was defined as women and men younger than 55 years old. The main end points of the study were 7-year all-cause mortality and 7-year major adverse cardiovascular and cerebrovascular events (MACCEs).
RESULTS
Of a total of 24 428 patients who underwent CABG, 7217 patients (men-to-women ratio ≈4:1) with premature isolated CABG were included. The median follow-up duration was 78.5 months (75.2–81.6 months). The prevalence rates of diabetes mellitus, hypertension, dyslipidaemia and obesity were significantly higher in women than in men (58.3% vs 28.6%, 64.2% vs 38.5%, 69.7% vs 55.3% and 44.7 vs 23.9, respectively; all Ps < 0.05). The risk factor burden (mean of the risk factor count per year) was also higher among the female population. Diabetes mellitus was the common mortality predictor between men and women. In the subgroup analysis (interaction analysis in the adjusted model), hypertensive females had a higher rate of MACCE and a higher rate of mortality than hypertensive males; however, this difference was not significant in the non-hypertensive population. Opium addiction was a strong predictor of MACCE and all-cause mortality among men. Female patients had a higher rate of 7-year MACCE (hazard ratio, 1.33; 95% confidence interval, 1.16–1.51) and a higher rate of 7-year all-cause mortality (hazard ratio, 1.23; 95% confidence interval, 0.98–1.53).
CONCLUSIONS
The risk factor profile and predictors of outcomes were different between our female and male patients. Women carried a higher risk of events and mortality after CABG at a young age.
A substantial body of evidence now indicates that the prevalence of coronary artery disease (CAD) is surprisingly increasing in young adults 1, 2.
The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain. O-GlcNAc is involved in ...diverse cellular processes ranging from the regulation of gene expression to stress response. Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases. Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer’s disease (AD) mouse models manifesting either tau or amyloid pathology. These data have stimulated interest in the possibility of using OGA-selective inhibitors as pharmaceuticals to alter the progression of AD. The mechanisms mediating the neuroprotective effects of OGA inhibitors, however, remain poorly understood. Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity. Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model. These results strongly suggest that OGA inhibitors act within brain through a mechanism involving enhancement of autophagy, which aids the brain in combatting the accumulation of toxic protein species. Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases. Moreover, these data suggest more targeted strategies to stimulate autophagy in an mTOR-independent manner may be found within the O-GlcNAc pathway. These findings should aid the advancement of OGA inhibitors within the clinic.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Background & Aim: The Covid‐19 pandemic has posed numerous ethical challenges to nurses and has exacerbated moral distress in clinical settings. Hence, due to the important role of nurses in ...pandemics, this study was conducted to investigate the severity and frequency of moral distress among nurses working in clinical settings at Maragheh teaching hospitals during the outbreak of COVID-19. Methods & Materials: This was a cross-sectional study conducted on 174 nurses working in surgical-medical, intensive care, pediatric and emergency wards of Maragheh hospitals in 2020-2021. Data were collected using a demographic form and the Corley’s Moral Distress Scale. Results: The median (Interquartile Range (IQR) = Q3 − Q1) of the severity and frequency of moral distress experienced were 54 (44-59) and 52 (43-58), respectively. The median of moral distress experienced in the intensive care and emergency wards were 56 (51-59) and 46 (43-51), which was more severe than that of in other wards. The median of frequency and severity of moral distress in men were 48 (41-59) and in women 50 (43-59), respectively, which was significantly higher than that of in women (P<0.001). The severity and frequency of moral distress had a statistically significant relationship with age, and work experience (P>0.05) so that with increasing age and work experience, the severity and frequency of moral distress decreased. Conclusion: Given the high frequency of moral distress among nurses during the COVID-19 pandemic in specific clinical settings, the use of management strategies in order to improve working conditions and create a positive setting can be helpful. It seems that holding courses on coping with moral distress in nurses in the context of the COVID-19 pandemic is an appropriate practical solution.
Abstract
Exposure to perinatal (prenatal and/or postnatal) stress is considered as a risk factor for metabolic disorders in later life. Accordingly, this study aimed to investigate the perinatal ...stress effects on the pancreatic endoplasmic reticulum (ER) stress induction, insulin secretion impairment and WFS1 (wolframin ER transmembrane Glycoprotein, which is involved in ER homeostasis and insulin secretion) expression changes, in rat offspring. According to the dams’ period of exposure to variable stress, their male offspring were divided into, control (CTRL); pre-pregnancy, pregnancy, lactation stress (PPPLS); pre-pregnancy stress (PPS); pregnancy stress (PS); lactation stress (LS); pre-pregnancy, pregnancy stress (PPPS); pregnancy, lactation stress (PLS); pre-pregnancy, lactation stress (PPLS) groups. Offspring pancreases were removed for ER extraction and the assessment of ER stress biomarkers, WFS1 gene DNA methylation, and isolated islets’ insulin secretion. Glucose tolerance was also tested. In the stressed groups, maternal stress significantly increased plasma corticosterone levels. In PPS, PS, and PPPS groups, maternal stress increased Bip (Hsp70; heat shock protein family A member 4), Chop (Ddit3; DNA- damage inducible transcript3), and WFS1 protein levels in pancreatic extracted ER. Moreover, the islets’ insulin secretion and content along with glucose tolerance were impaired in these groups. In PPS, PS, LS and PPPS groups, the pancreatic glucocorticoid receptor (GR) expression increased. Maternal stress did not affect pancreatic WFS1 DNA methylation. Thus, maternal stress, during prenatal period, impaired the islets’ insulin secretion and glucose homeostasis in adult male offspring, possibly through the induction of ER stress and GR expression in the pancreas, in this regard the role of WFS1 protein alteration in pancreatic ER should also be considered.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction. In late February 2020, after we had informed about the presence of some cases of COVID-19 in Iran and its rapid spread throughout the country, we decided to make the necessary ...arrangements for patients with critical conditions in Pediatric Intensive Care Unit (PICU) at Children's Medical Center. There are a little data on critically ill children with COVID-19 infection with ICU requirements. The aim of this study was to describe clinical characteristics, laboratory parameters, treatment, and outcomes of the pediatrics population infected by SARS-CoV-2 admitted to PICU. Materials and Methods. This study was performed between February 2020 and May 2020 in the COVID PICU of the Children’s Medical Center Hospital in Tehran, Iran. Patients were evaluated in terms of demographic categories, primary symptoms and signs at presentation, underlying disease, SARS-CoV-2 RT-PCR test result, laboratory findings at PICU admission, chest X-ray (CXR) and lung CT findings, and treatment. Moreover, the need to noninvasive ventilation (NIV) or mechanical ventilation, the length of hospital stay in the PICU, and outcomes were assessed. Results. In total, 99 patients were admitted to COVID PICU, 42.4% (42 patients) were males, and 66 patients had positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR). There was no statistically significant difference in the frequency of clinical signs and symptoms (except for fever) among patients with positive SARS-CoV-2 RT-PCR and negative ones. Among all admitted patients, the presence of underlying diseases was noticed in 81 (82%) patients. Of 99 patients, 34 patients were treated with NIV during their admission. Furthermore, 35 patients were intubated and treated with mechanical ventilation. Unfortunately, 11 out of 35 mechanically ventilated patients (31%) passed away. Conclusion. No laboratory and radiological findings in children infected with COVID-19 were diagnostic in cases with COVID-19 admitted to PICU. There are higher risks of severe COVID-19, PICU admission, and mortality in children with comorbidities.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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