Background:Millions of people in the world have diabetes mellitus and its prevalence is growing. Oxidative stress, advanced glycation end-products (AGEs) and receptor for advanced glycation end-products (RAGE) play key role in the pathogenesis of diabetes. New and safe strategies of remedy are needed for this disease.Objectives:We hypothesized that resveratrol may exert a renal protective effect on diabetic rats.Materials and Methods:Male rats with diabetes were treated with or without resveratrol as 1, 5, 10 mg/kg of body weight for 30 days. The total AGEs and malondialdehyde levels in kidney tissues were determined by spectrofluorimetric method and the insulin level was assayed using ELISA. The total antioxidant capacity contents in kidney and the glucose in plasma were measured by a colorimetric assay. The expression of RAGE was assayed in kidneys of all animals using quantitative PCR.Results:In resveratrol-treated rats with diabetes, malondialdehyde levels, plasma glucose and expression of RAGE were significantly reduced compared with the untreated group. Moreover, the total antioxidant and insulin levels significantly increased in treated rats. There was no significant difference in the AGEs contents among all the groups.Conclusions:These results revealed that resveratrol has beneficial effects on kidney by extenuating the oxidative stress and down-regulation of RAGE expression.
There is no denying that the massive spread of COVID-19 around the world has worried everyone. The virus can cause mild to severe symptoms in various organs, especially the lungs. The virus affects oxidative stress in the cells. Reactive Oxygen Species modulator 1 (ROMO1) is one of the most important mitochondrial proteins that plays a critical regulatory role in the production of Reactive Oxygen Species (ROS). According to the studies, COVID-19 can promote oxidative stress through some important pathways, for instance, TNF-α and NF-κB routes. Furthermore, ROMO1 is closely related to these pathways and its dysfunction may affect these routes, then promote oxidative stress, and ultimately cause tissue damage, especially in the lungs. Another factor to consider is that the TNF-α and NF-κB pathways are associated with ROMO1, COVID-19, and oxidative stress. To summarize, it is hypothesized that COVID-19 may increase oxidative stress by affecting ROMO1. Understanding the exact molecular mechanisms of ROMO1 in the pathogenesis of COVID-19 can pave the way to find better therapeutic strategies.
The incidence of diabetes mellitus is rapidly increasing in the world. One of the complications of diabetes includes disturbance of the reproductive tract, such as infertility, erectile dysfunction, and endocrine disruption. Nitric oxide (NO) is a free radical produced by most cells including the human male and female reproductive tracts. NO has a dual role where low concentrations are essential for homeostatic cellular biology and physiology, but high levels have detrimental effects relating to cellular damage from this reactive oxygen species (ROS). 8-hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside of DNA that is currently used as a biomarker of cellular oxidative stress, where urinary levels can correlate with diabetic nephropathy and retinopathy. Our aim was to investigate the relationship between nitrate/nitrite levels and 8-OHdG levels in the semen of diabetic and non-diabetic men. Concentrations of nitrate/nitrite and 8-OHdG were examined in seminal plasma of 32 diabetic and 35 non-diabetic men. The level of nitrate/nitrite was assayed by colorimetric reaction and 8-OHdG was measured by ELISA. Our results showed that the seminal plasma nitrate/nitrite levels were significantly higher in the diabetic group (p < 0. 01). There were also significantly higher 8-OHdG levels in diabetic men compared to non-diabetic men (p < 0.05). Regression analysis indicated that in diabetic men, nitrate/nitrite levels correlated well with 8-OHdG levels (r = 0.64, p < 0.001). A significant trend between nitrate/nitrite and sperm parameters was not observed. Our data suggests that high levels of nitrate/nitrite in the semen of diabetic men is suggestive of reactive oxygen species induced DNA damage that is correlated with 8-OHdG levels but not sperm parameters. These results support the further investigation of NO and 8-OHdG as biomarkers for assessing male infertility.
The equivalent statistical methods, spectral analysis, and time history analysis are usually offered in the steel structure design regulations. Among these methods, the third one is more accurate; however, it requires more time to align the accelerometers due to a large number of analyses. In the endurance time (ET) method, incremental acceleration functions gradually and uniformly increases over time while their linear and nonlinear response spectra are proportional to the mean of the real seismic spectrum. These functions are used as input functions to analyze the nonlinear time history of structures, and the performance of structures is evaluated based on the maximum length of time they can meet specified performance goals. A three-story steel bending frame with (slotted web) SW and (web unslotted flange) WUF connection is examined through the performance time method in performance-based design. This article aimed at evaluating the seismic performance of these connections in the bending frame through endurance time analysis to predict the structural response in the probabilistic evaluation of the seismic performance of the structures. It is found that the endurance time analysis is justified with the seismic performance of the connections with low computational cost and proper accuracy. The results of comparing both SW and WUF connections indicated that the SW connection prevents the connection welding area from being failed due to transferring the plastic joint into the beam and in an area away from the column face and causes less damage compared to the WUF connection.
BackgroundExtensive research has increased our understanding of the molecular alterations needed for non-small cell lung cancer (NSCLC) development. Deregulation of a pathway including MYCN, HMGA2 and CDKN2A, with the participation of DICER1, is of importance in several solid tumours, and may also be of significance in the pathogenesis of NSCLC.MethodsGene expression of MYCN, HMGA2, CDKN2A and DICER1 were investigated with RT-qPCR in surgically resected NSCLC tumour tissue from 175 patients. Expression of the let-7 microRNA family was performed in 78 adenocarcinomas and 16 matching normal lung tissue samples using microarrays. The protein levels of HMGA2 were determined by immunohistochemistry in 156 tumour samples and the protein expression was correlated with gene expression. Associations between clinical data, including time to recurrence, and expression of mRNA, protein and microRNAs were analysed.ResultsCompared to adenocarcinomas, squamous cell carcinomas had a median 5-fold increase in mRNA expression of HMGA2 (p = 0.003). A positive correlation (r = 0.513, p < 0.010) between HMGA2 mRNA expression and HMGA2 protein expression was seen. At the protein level, 90 % of the squamous cell carcinomas expressed high levels of the HMGA2 protein compared to 47 % of the adenocarcinomas (p < 0.0001). MYCN was positively correlated with HMGA2 (p < 0.010) and DICER1 mRNA expression (p < 0.010), and the expression of the let-7 microRNAs seemed to be correlated with the genes studied. MYCN expression was associated with time to recurrence in multivariate survival analyses (p = 0.020).ConclusionsA significant difference in HMGA2 mRNA expression between the histological subtypes of NSCLC was seen with a higher expression in the squamous cell carcinomas. This was also found at the protein level, and we found a good correlation between the mRNA and the protein expression of HMGA2. Moreover, the expression of MYCN, HMGA2, and DICER1 seems to be correlated to each other and the expression of the let7-genes impacted by their expression. MYCN gene expression seems to be of importance in time to recurrence in this patient cohort with resected NSCLC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2104-9) contains supplementary material, which is available to authorized users.
Introduction:Studies suggest that ATP-sensitive potassium (KATP) channels are a potential pharmacotherapeutic target for neuroprotection in neurodegenerative diseases. The current study aimed at evaluating the effect of pretreatment with glibenclamide (Glib) and B vitamins supplement on the severity of behavioral symptoms in 6-hydroxydopamine (OHDA)-induced Parkinsonism. Also malondialdehyde (MDA) concentration was measured in the blood and brain suspensions to find probable neuroprotective mechanism of Glib.Methods:The 6-OHDA was injected into striatum of rats by stereotaxic surgery. Treatment with Glib and B vitamins was started before the surgery and continued up to 3 weeks after that. Development and severity of Parkinsonism were evaluated by conventional behavioral tests. MDA values were measured spectrophotometrically using thiobarbituric acid and MDA standard curve.Results:Pretreatments with Glib, at both doses of 1 and 5 mg/kg or B vitamins significantly ameliorated severity of the behavioral symptoms. Pretreatment with a combination of Glib and B vitamins was more effective than pretreatment with Glib or B vitamins alone. Also, pretreatment with B vitamins, Glib, or a combination of them reduced MDA concentration in the brain suspensions. Decrease in MDA concentration in the group of rats that received a combination of B vitamins and Glib was more prominent than that of the Glib groups.Conclusion:As severity of the behavioral symptoms in the 6-OHDA-induced Parkinsonism reflects the degree of the lesion in Substantia Nigra (SN) dopaminergic neurons, it is suggested that Glib pretreatment has neuroprotective effect against 6-OHDA-induced neurotoxicity. The current study data also showed that this effect may be mediated by antioxidant effect of Glib.
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