Protective effects of boron and vitamin E on ethylene glycol-induced renal crystal calcium deposition in rat

Objectives. Kidney stone disease is a common form of renal disease. Antioxidants, such as vitamin E (Vit E) and boron, are substances that reduce the damage caused by oxidation. Methods. Adult male rats were divided into 5 groups (n=6). In group 1, rats received standard food and water for 28 days (control group); in group 2, standard rodent food and water with 0.75 ethylene glycol/d (dissolved in drinking water) (EG Group); in group 3, similar to group 2, with 3 mg of boron/d (dissolved in water) (EG+B Group); in group 4, similar to group 2, with 200 IU of vitamin E injected intraperitoneally on the fi rst day and the 14th day, (EG+Vit E Group); in group 5, mix of groups 3 and 4, respectively (EG+B+Vit E Group). Results. Kidney sections showed that crystals in the EG group increased signifi cantly in comparison with the control group. Crystal calcium deposition score in groups of EG+B (160), EG+Vit E, and EG+B+Vit E showed a significant decrease compared to EG group. Measurement of the renal tubules area and renal tubular epithelial histological score showed the highest signifi cant dilation in the EG group. Tubular dilation in the EG+B+Vit E group decreased compared to the EG+B and EG+Vit E groups. Conclusions. Efficient effect of boron and Vit E supplements, separately and in combination, has a complimentary effect in protection against the formation of kidney stones, probably by decreasing oxidative stress. � 2016, De Gruyter Open Ltd. All Rights Reserved

Magnetic resonance imaging radiomic feature analysis of radiation-induced femoral head changes in prostate cancer radiotherapy

Background and Purpose: As a feasible approach, radiotherapy has a great role in prostate cancer (Pca) management. However, Pca patients have an increased risk of femoral head damages including fractures after radiotherapy. The mechanisms of these complications are unknown and time of manifestations is too long; however, they may be predicted by early imaging. The main purpose of this study was to assess the early changes in femoral heads in Pca patients treated with intensity-modulated radiation therapy (IMRT) using multiparametric magnetic resonance imaging (mpMRI) radiomic feature analysis. Materials and Methods: Thirty Pca patients treated with IMRT were included in the study. All patients underwent two mpMRI pre- and postradiotherapy. Thirty-four robust radiomic features were extracted from T1, T2, and apparent diffusion coefficient (ADC) obtained from diffusion-weighted images. Wilcoxon signed-rank test was performed to assess the significance of the change in the mean T1, T2, and ADC radiomic features postradiotherapy relative to preradiotherapy values. The percentage change values were normalized based on the natural logarithm base ten. Features were also ranked based on their median changes. Results: Sixty femoral heads were analyzed. All radiomic features have undergone changes. Significant postradiotherapy radiomic feature changes were observed in 20 and 5 T1- and T2-weighted radiomic features, respectively (P < 0.05). ADC features did not vary significantly postradiotherapy. The mean radiation dose received by femoral heads was 40 Gy. No fractures were observed within the follow-up time. Different features were found as high ranked among T1, T2, and ADC images. Conclusion: Early structural change analysis using radiomic features may contribute to predict postradiotherapy fracture in Pca patients. These features can be identified as being potentially important imaging biomarkers for predicting radiotherapy-induced femoral changes. © 2019 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow

Effect of thrombin peptide 508 (TP508) on bone healing during distraction osteogenesis in rabbit tibia

Thrombin-related peptide 508 (TP508) accelerates bone regeneration during distraction osteogenesis (DO). We have examined the effect of TP508 on bone regeneration during DO by immunolocalization of Runx2 protein, a marker of osteoblast differentiation, and of osteopontin (OPN) and bone sialoprotein (BSP), two late markers of the osteoblast lineage. Distraction was performed in tibiae of rabbits over a period of 6 days. TP508 (30 or 300 μg) or vehicle was injected into the distraction gap at the beginning and end of the distraction period. Two weeks after active distraction, tissue samples were harvested and processed for immunohistochemical analysis. We also tested the in vitro effect of TP508 on Runx2 mRNA expression in osteoblast-like (MC3T3-E1) cells by polymerase chain reaction analysis. Runx2 and OPN protein were observed in preosteoblasts, osteoblasts, osteocytes of newly formed bone, blood vessel cells and many fibroblast-like cells of the soft connective tissue. Immunostaining for BSP was more restricted to osteoblasts and osteocytes. Significantly more Runx2- and OPN-expressing cells were seen in the group treated with 300 μg TP508 than in the control group injected with saline or with 30 μg TP508. However, TP508 failed to increase Runx2 mRNA levels significantly in MC3T3-E1 cells after 2–3 days of exposure. Our data suggest that TP508 enhances bone regeneration during DO by increasing the proportion of cells of the osteoblastic lineage. Clinically, TP508 may shorten the healing time during DO; this might be of benefit when bone regeneration is slow

Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

Background Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. Methods The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Results Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated cell-derived xenografts compared to paclitaxel only-treated cell derived xenografts. Conclusions This proof of principle study demonstrates that inhibition of the JAK2/STAT3 pathway by the addition of CYT387 suppresses the ‘stemness’ profile in chemotherapy-treated residual cells in vitro, which is replicated in vivo, leading to a reduced tumor burden. These findings have important implications for ovarian cancer patients who are treated with taxane and/or platinum-based therapies. Keywords: Ovarian carcinoma, Cancer stem cell, Metastasis, Ascites, Chemoresistance, Recurrence, JAK2/STAT3 pathwa

Seismic risk analysis of Iranian construction projects

In this paper, the project earthquake occurrence risk coefficient is determined for each construction project that is located in one of Iran's twenty seismic regions. This coefficient is allocated, regardless of the current situation of the project, being in the plan or execution phase or even completed. This coefficient indicates the possibility of an earthquake occurrence during a project's life time. To find this coefficient, the Gutenberg-Richter linear relationship has been applied, in conjunction with the Poisson distribution. The Gutenberg-Richter linear equation expresses the relationship between the magnitude of an earthquake and the number of occurrences, during a fixed time, of that magnitude. To find the linear relationship for a series of earthquakes with different magnitudes occurring in the same seismic region, the Ordinary Least Square (OLS) has been used. Two linear regression assumption violations, which are variance heteroscedasticity and autocorrelation, have been tested on the available data. In the case of finding one or both of these two violations, The Generalized Least Square (GLS) has been applied to produce a better regression line. Moreover, the second order type of the Gutenberg-Richter relationship has also been determined to validate the linear one. In conclusion, by application of the Poisson distribution and by having the design earthquake's magnitude and project life time, the third parameter, which is the design earthquake occurrence risk, can be determined for a given construction project in a specific location in Iran.M. Shokri-Ghasabeh, A. Bakhshiani, M. Mofid and K. Hanse

Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily.

The Bacillus subtilis Sfp protein activates the peptidyl carrier protein (PCP) domains of surfactin synthetase by transferring the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to a serine residue conserved in all PCPs. Its wide PCP substrate spectrum renders Sfp a biotechnologically valuable enzyme for use in combinatorial non-ribosomal peptide synthesis. The structure of the Sfp-CoA complex determined at 1.8 A resolution reveals a novel alpha/beta-fold exhibiting an unexpected intramolecular 2-fold pseudosymmetry. This suggests a similar fold and dimerization mode for the homodimeric phosphopantetheinyl transferases such as acyl carrier protein synthase. The active site of Sfp accommodates a magnesium ion, which is complexed by the CoA pyrophosphate, the side chains of three acidic amino acids and one water molecule. CoA is bound in a fashion that differs in many aspects from all known CoA-protein complex structures. The structure reveals regions likely to be involved in the interaction with the PCP substrate

Rectal wall MRI radiomics in prostate cancer patients: prediction of and correlation with early rectal toxicity

Purpose: To investigate MRI radiomic analysis to assess IMRT associated rectal wall changes and also for predicting radiotherapy induced rectal toxicity. Material and methods: At first, a machine learning radiomic analysis was applied on T2-weighted (T2W) and apparent diffusion coefficient (ADC) rectal wall MR images of prostate cancer patients� pre- and post-IMRT to predict rectal toxicity. Next, Wilcoxon singed ranked test was performed to find radiomic features with significant changes pre- and post-IMRT. A logistic regression classifier was used to find correlation between features with significant changes and radiation toxicity. Area under the curve (AUC) of receiver operating characteristic (ROC) curve was used in two levels of study for finding performances. Results: AUCmean, 0.68 ± 0.086 and 0.61 ± 0.065 were obtained for pre- and post-IMRT T2 radiomic models, respectively. For ADC radiomic models, AUCmean was 0.58 ± 0.034 for pre-IMRT and was 0.56 ± 0.038 for post-IMRT. Wilcoxon-signed rank test revealed that 9 T2 radiomic features vary significantly post-IMRT. The AUC of logistic-regression was in the range of 0.46�0.58 for single significant features and was 0.81 when all significant features were combined. Conclusions: Pre-IMRT MR image radiomic features could predict rectal toxicity in prostate cancer patients. Radiotherapy associated complications may be assessed by studying the changes in the MR radiomic features. © 2018, © 2018 Taylor & Francis Group, LLC

MRI Radiomic Analysis of IMRT-Induced Bladder Wall Changes in Prostate Cancer Patients: A Relationship with Radiation Dose and Toxicity

Background: The main purpose of this study was to assess the structural changes in the bladder wall of prostate cancer patients treated with intensity-modulated radiation therapy using magnetic resonance imaging texture features analysis and to correlate image texture changes with radiation dose and urinary toxicity. Methods: Ethical clearance was granted to enroll 33 patients into this study who were treated with intensity-modulated radiation therapy for prostate cancer. All patients underwent two magnetic resonance imagings before and after radiation therapy (RT). A total of 274 radiomic features were extracted from MR-T2W�weighted images. Wilcoxon singed rank-test was performed to assess significance of the change in mean radiomic features post-RT relative to pre-RT values. The relationship between radiation dose and feature changes was assessed and depicted. Cystitis was recorded as urinary toxicity. Area under receiver operating characteristic curve of a logistic regression�based classifier was used to find correlation between radiomic features with significant changes and radiation toxicity. Results: Thirty-three bladder walls were analyzed, with 11 patients developing grade �2 urinary toxicity. We showed that radiomic features may predict radiation toxicity and features including S5.0SumVarnc, S2.2SumVarnc, S1.0AngScMom, S0.4SumAverg, and S5. 5InvDfMom with area under receiver operating characteristic curve 0.75, 0.69, 0.65, 0.63, and 0.62 had highest correlation with toxicity, respectively. The results showed that most of the radiomic features were changed with radiation dose. Conclusion: Feature changes have a good correlation with radiation dose and radiation-induced urinary toxicity. These radiomic features can be identified as being potentially important imaging biomarkers and also assessing mechanisms of radiation-induced bladder injuries. © 201