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Sajad Borzoueisileh,1,2 Ali Shabestani Monfared,3 Hossein Ghorbani,4 SMJ Mortazavi,5 Ebrahim Zabihi,1 Mehdi Pouramir,1 Mohsen Shafiee,6 Fatemeh Niksirat7 1Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 2Student Research Committee, Babol University of Medical Sciences, Babol, Iran; 3Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 4Pathology Department, Babol University of Medical Sciences, Babol, Iran; 5Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; 6Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran; 7Department of Medical Physics Radiobiology and Radiation Protection, School of Medicine, Babol University of Medical Sciences, Babol, IranCorrespondence: Ali Shabestani MonfaredCancer Research Center, Babol University of Medical Sciences, Ganjafrooz St., Babol, IranTel +989111230475Fax +981135289733Email monfared_ali@yahoo.comPurpose: Biochemical and histopathological properties of renal tissues were reported to be affected by both radiofrequency electromagnetic fields (RF-EMF) and ionizing radiation. The radiation-induced changes in the kidney, including the serum levels of blood urea nitrogen (BUN) and creatinine (Cr), could lead to adverse health outcomes such as chronic kidney disease. These complications signify the importance of the research in this field. Thus, in this study, the effects of ionizing and non-ionizing radiations, as well as their combination, were assessed by evaluating the alteration in BUN, Cr, and histopathological changes in kidney tissue.Materials and Methods: Ninety-six male Wistar rats were randomly divided into six groups and were exposed to either 900/1800MHz (mobile phone) or 2.4 GHz RF-EMF (Wi-Fi) radiation for 14 days, 8Gy x-ray, or their combination. Sera were collected from 2 mL of rat blood, then BUN and Cr levels were determined. Also, renal samples were stained with hematoxylin and eosin and evaluated histopathologically.Results: Both BUN and Cr levels raised non-significantly after exposure to 8 Gy x-rays. Moreover, all measurements in the samples of x-ray groups were in borderline or higher than normal values. The BUN levels of control, Wi-Fi, x-ray, and Wi-Fi+x-ray groups were not significantly different. However, Cr levels in the Wi-Fi group were significantly higher than those of the controls, and BUN to Cr ratio levels were significantly lower than those of the controls. Also, tubular atrophy and vessel wall thickening were associated with these exposures.Conclusion: Exposure to 900/1800MHz, 2400 MHz EMF can alter the kidney function. However, pre-exposure to 900/1800MHz EMF could modulate the acute adverse effects of lethal x-ray dose, which addresses the adaptive response in the kidney.Keywords: EMF, RF, kidney, mobile phone radiation, Wi-Fi radiation

Introduction: The current study investigated the combination of high Z atoms (iodine-, platinium-based drugs) with using low energy irradiation (120kvp) in Anaplastic Thyroid cancer cells. Material and Methods: For this purpose, eight groups were designed: control (CNT), different concentrations of Iodine contrast media (ICM), irradiation with various doses, Cis-platin (CDDP) with different concentrations, (ICM + CDDP), (ICM + RAD), (CDDP + RAD) and (ICM + CDDP + RAD). The viability was measured by MTT and Colony assay. In MTT assay, the viability of 8305c cells RAD (2 Gy)+ICM (10mg/mL) group was significantly lower than those treated with RAD or ICM alone. CDDP +ICM+RAD group significantly decreased the viability. In colony assay, cells in ICM + RAD (2 Gy) group reduced the number of colonies more significant than RAD group. The difference of colony forming ability between CDDP and CDDP + RAD (2 Gy) was significant. The difference of ICM + CDDP + RAD (2 Gy) and CDDP +RAD (2 Gy) group was significant. All data were statistically analysed using one-way analysis of variance (ANOVA) followed by Chafe’s multi-comparisons tests. All data were presented as mean ± standard deviation (SD) and analysed using statistical package for social sciences (SPSS 16). Significance was considered to be p

Background and Objective: Agricultural toxins including organochlorine and organophosphorus families cause damages in the various tissues in humans. Diazinon is a non-systemic organophosphate insecticide. This study was carried out to determine the effect of Diazinon on sex hormone, interferon gamma, interleukin-4 and 10 in male rats. Methods: In this experimental study 24 adult male Wistar rats were randomly allocated into four groups. Three experimental groups were received Diazinon 5 days per week for one month at 0.3, 3 and 30 mg/kg/bw intraperitoneally, while controls received nothing. Seven days after the last injection, blood samples were obtained and the serum testosterone, FSH, LH, interferon gamma, interleukin-4 and interleukin-10 were measured. Results: Serum level of Interleukin-10 significantly increased in experimental group (30 mg/kg/bw of Diazinon) compared to controls (P

Background: Amitriptyline is one of the most common tricyclic antidepressants, which binds to pain sensory nerve fibers close to the sodium channel; hence, it could interact to some degree with receptors of local anesthetics. This study was designed to assess the additional analgesic effects of 2% Amitriptyline local gel administration in irreversible pulpitis pain of the molars. Materials and Methods: This study was a randomized, double-blind clinical trial that was performed on 56 consented adult patients who did not receive enough analgesia after a lidocaine nerve block for their tooth pulpitis pain. Patients were treated with 0.2 ml of either 2% amitriptyline or placebo, which was directly injected into their mandibular molar pulp chamber after they had received two routine lidocaine injections. Patients were asked to score their pain as a mark on a 10-cm Visual Analogue Scale (VAS) at different timepoints: 0 (just before gel administration), 1, 3, 5, 7, and 9 minutes after the treatments. Results: There was a 92.5% decrease in VAS scores of patients 9 minutes after amitriptyline administration compared to Time 0, while in the placebo group this difference was only 13.5%. Further, in the amitriptyline group, the VAS score at all timepoints was statistically different from Time 0 ( P < 0.01). The overall pain reduction and its trend was significantly higher in the amitriptyline group compared with the placebo group ( P < 0.001). Conclusion: Inter-pulp space administration of amitriptyline 2% gel for completing analgesia in irreversible pulpitis pain could be effective and useful as a conjunctive therapy to injections of local anesthetics.

Metal-Organic Framework-199 (MOF-199) is a subgroup of MOFs that is utilized in different medical fields such as drug delivery. In the current study, the effect of sub-acute exposure to MOF-199 on spatial memory, working memory, inflammatory mediators' expression, and oxidative stress level of brain tissue has been investigated. Thirty-two male Wistar rats were randomly divided into four groups as vehicle, MOF-199 at doses 0.3, 3, or 6 mg/kg. After four injections of relevant interventions via tail vein during 14 days, behavioral parameters were investigated using Y-maze and Morris Water Maze (MWM) tests. Oxidative stress was measured by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) tests. The expression levels of TNF-α and IL-1β were assessed by quantitative real-time reverse-transcription PCR (qRT-PCR). No significant differences were observed in working memory, spatial learning and memory of MOF-199 receiving rats. Additionally, the level of oxidative stress and inflammatory genes expression were not remarkably changed in the brain tissues of MOF-199 treated rats. Despite the lack of remarkable toxic effects of sub-acute exposure to MOF-199, more studies with a longer duration of administration are necessary to use this substance for drug delivery systems in diseases related to the nervous system., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maryam Ghasemi-Kasman reports financial support was provided by Babol University of Medical Sciences. Maryam Ghasemi-Kasman reports a relationship with Babol University of Medical Sciences that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Benzo(a)pyrene (BaP), an environmental toxicant and endocrine disruptor, has been shown to exacerbate atherosclerosis when combined with a high-fat diet. Fibroblast Growth Factor-21 (FGF21), a novel hormone with anti-atherosclerotic properties, is associated with the presence of atherosclerosis and reduces plaque formation in experimental animals., Objectives: The present study aimed to investigate the chronic effect of BaP injection on hepatic FGF21 expression, as an anti-atherosclerotic hormone, in mice fed with or without an atherogenic diet (AtD)., Methods: Eighteen C57BL/6J male mice (6 weeks) were randomly divided into six groups based on the dosage and diet. Blood samples were collected, and serum cholesterol, triglyceride, HDL-C, LDL-C, and glucose levels were measured. FGF21 expression was assessed by quantitative real-time PCR. Atherosclerotic lesions in mice were studied with Oil Red O (ORO) staining., Results: Benzo(a)pyrene causes a significant increase in liver FGF21 expression in a dose-dependent manner, and BaP co-exposure with AtD leads to a further increase in FGF21 expression. Additionally, the addition of BaP to AtD significantly increased the serum glucose, cholesterol, and LDL-C levels and accelerated the formation of atherosclerotic lesions. Besides, our findings showed that there is a significant positive correlation between FGF21 expression and glucose, cholesterol, LDL-C, and ORO-positive areas., Conclusions: Our findings revealed that BaP increases the expression of endogenous FGF21 in treated animals as a compensatory response to protect the heart from atherosclerosis induced by BaP and AtD., Competing Interests: The authors declare no competing interests., (Copyright © 2024, Shanehbandpour-Tabari et al.)

Bleomycin (BL) is a widely used anticancer drug that can cause pulmonary fibrosis due to increased fibroblast proliferation and increased secretion of extracellular matrix. RASSF1A is a tumor suppressor gene that is down-regulated by DNA methylation during fibrosis. Disulfiram (DSF), a noncytosine DNA methyltransferase inhibitor, can revert epigenetic biomarkers and re-express silenced genes. We investigated anti-inflammatory and anti-fibrotic effects of DSF on regulation of epigenetic molecules and histopathology in a rat model of BL induced pulmonary fibrosis. We used six groups of rats: sesame oil (SO) control (Co) group, BL group, BL + SO group and three BL + DSF groups administered 1 mg/kg DSF (BL + DSF), 10 mg/kg DSF (BL + DSF10) or 100 mg/kg DSF (BL + DSF100), respectively. BL was administered intratracheally to induce pulmonary fibrosis. DSF and SO were injected intraperitoneally (i.p.) 2 days before BL administration; these injections were continued for 3 weeks. At the end of the study, lung tissues were removed for molecular and histopathologic studies. Administration of 10 or 100 mg/kg DSF after BL induced pulmonary inflammation and fibrosis, and up-regulated RASSF1A and down-regulated TNF-α and IL-1 β compared to the BL and BL + SO groups. A RASSF1A unmethylated band was observed using the methylation-specific PCR technique in rats that had been administered 10 and 100 mg/kg DSF, which indicated partial DNA demethylation. Histopathologic evaluation revealed that fibrosis and all inflammatory scores were decreased significantly in the BL + DSF10 and BL + DSF100 groups compared to the BL group. Our findings indicate that DSF modified DNA methylation by up-regulating RASSF1A , which reduced inflammation and fibrosis in BL induced pulmonary inflammation and fibrosis.

Oximes, as classical acetylcholinesterase (AChE) reactivators, have some pharmacokinetics/pharmacodynamics disadvantages. During the synthesis of non-oxime compounds, we encountered the compound 2-formylbenzoic acid (2-FBA) with promising in vitro and in vivo cholinesterase (ChE) reactivating properties in the acute exposure to diazinon (DZN). For in vitro experiments, the healthy mice serum and brain homogenate were freshly prepared and exposed to DZN (160 µg/mL). After 10 minutes, 2-FBA was added to the poisoned samples, and ChE activity was measured afterward. For the in vivo assay, the mice were poisoned with DZN subcutaneous (SC) injection (50 mg/kg), and after 1 hour, either 2-FBA or Pralidoxime (2-PAM) was injected intravenously (IV). After 3 h, ChE activity was measured in the serum and brain homogenate samples. The LD50 (IV) for 2-FBA in mice was measured as well. 2-FBA effectively reactivated the inhibited ChE in serum and brain homogenate samples in vitro. In the in vivo experiments, while 2-FBA could significantly reactivate the brain ChE even better than 2-PAM, they failed to reactivate the serum ChE by single IV injection. LD50 of 2-FBA was calculated to be 963 mg/kg. There were no general toxicity signs in any treatment groups. The in silico results support the potential ability of 2-FBA efficacy via possibly Witting reaction mechanism. Our findings indicate that 2-FBA seems to be a suitable non-oxime candidate for AChE reactivation with minimal side effects. Further toxicokinetic studies on this compound are strongly recommended to be performed before conducting the clinical trial in humans., Competing Interests: The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

One of the major challenges in gastric cancer (GC) chemotherapy is the phenomenon of multi-drug resistance (MDR). The epithelial-mesenchymal transition (EMT) and its key molecules, transforming growth factor-β (TGFβ) and SMAD2, play a central role in MDR occurrence. Tamoxifen (TAM), a triphenylethylene derivative, can overcome MDR in human gastric cancers. The aim of this study was to investigate the effect of TAM on 5-FU resistance of GC by suppressing the TGFβ1/SMAD2 signaling pathway and EMT. The MKN-45 cell line was subjected to treatment with 5-FU, TAM and a combination of both. The MTT assay was used to investigate the cytotoxic effects of 5-FU and TAM, and the DNA laddering technique was used to assess DNA fragmentation and apoptosis. Real-time RT-PCR examined the change in gene expression in EMT-related genes (SNAI2, VIM, TGFβ1 and SMAD2) . The results of the present study indicated that not only TAM treatment significantly decreased the IC50 of 5-FU (P≤0.05), but also the addition of TAM to 5-FU induced apoptosis in the MKN-45 cell line. Treatment with TAM and 5-FU significantly inhibited TGFβ1 and TGFβ1-induced expression of EMT markers (VIM and SNAI2) in MKN-45 cells (P≤0.05). The reduction of TGFβ1 targets downstream of the SMAD2 signaling pathway reversed the process of EMT and significantly increased the sensitivity of MKN-45 cells to 5-FU. The results of the present study suggested that reversal of EMT-mediated MDR via the TGFβ1/SMAD signaling pathway using TAM may be a potential new therapeutic strategy to overcome chemoresistance to 5-FU during GC chemotherapy., (© The Author(s).)

Background: Some evidence shows that a pre-exposure to RF can mitigate the effects of subsequent exposures to high doses of ionizing radiation., Objective: We aimed to assess the effect of a pre-exposure to non-ionizing RF radiation on survival, weight changes, food consumption, and water intake of lethally irradiated rats., Material and Methods: In this case-control study, we used a commercial mobile phone (GSM, 900/1800 MHz) as well as a 2.4 GHz Wi-Fi router as the sources of pre-exposure to RF radiation. Forty-eight rats were randomly divided into six groups of control, "8 Gy X-rays", mobile phone, "mobile phone+8 Gy", Wi-Fi, and "Wi-Fi+8 Gy". Then, the survival fraction, weight loss, water, and food consumption changes were compared in different groups., Results: The survival analysis indicated that the survival rates in all of the exposed animals ("8 Gy X-rays", "mobile phone+8 Gy", "Wi-Fi+8 Gy") were significantly lower than the control, "Wi-Fi", and "mobile phone" groups. The changes in survival rates of "mobile+8 Gy", "Wi-Fi+8 Gy", and 8 Gy alone were not statistically significant. However, food and water intake were significantly affected by exposure to both RF pre-exposures and exposure to high dose ionizing radiation., Conclusion: To the best of our knowledge, the existence of a dose window for the induction of AR can be the cause of the lack of AR in our experiment. Our findings confirm that in a similar pattern with the adaptive responses induced by pre-exposure to ionizing radiation, the induction of adaptive response by RF-pre-exposures requires a minimum level of damage to trigger adaptive phenomena., Competing Interests: None, (Copyright: © Journal of Biomedical Physics and Engineering.)

Statement of the Problem: Squamous cell carcinoma (SCC) comprises over 90% of oral malignancies. Cisplatin, as a selective chemotherapy agent to treat SCC, has many side effects despite its high effectiveness. There are some studies on the effects of bromelain derived from pineapple stems on different malignancies., Purpose: The aim of this study was to investigate the effect of bromelain alone and in combination with Cisplatin on oral squamous cell carcinoma (OSCC) and fibroblast cell lines., Materials and Method: In this interventional study, the HN5 cell line of OSCC and fibroblast cell line were treated with different concentrations of bromelain alone and in combination with cisplatin. Cell viability test was performed after 24, 48 and 72 hours using MTT (3-)4,5-dimethylthiazol-2-yl(-2,5 diphenyl tetrazolium bromide) assay. In the final stage, the drug-treated cells underwent flow cytometry to assess apoptosis patterns. Data were analyzed using SPSS 17, ANOVA (for general comparison of groups) and LSD post hoc tests (for comparison two groups). p< 0.05 was considered statistically significant., Results: The findings suggested that although bromelain showed toxic effects on HN5 cancer cells, its combination with Cisplatin resulted in little improvement in its effectiveness. Bromelain alone and in combination with Cisplatin presented cytotoxic effects against fibroblasts, which depended on the dosage and time exposure (p< 0.05). The flow cytometry results did not support the superior effect of the combination of two medications over Cisplatin alone (p> 0.05)., Conclusion: According to the findings, although adding bromelain to Cisplatin reduced toxicity on normal tissues, the combination of these two drugs did not increase the anticancer effect of Cisplatin. Thus, bromelain in combination with Cisplatin is not recommended as an adjuvant drug for OSCC., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © Journal of Dentistry.)

It has been well known that oxidative stress and increased intracellular reactive oxygen species (ROS) have a pivotal role in disrupting the insulin signaling pathways leading to cellular insulin resistance. In this study, we evaluated arbutin's effects on glucose uptake by GLUT4 and cytoprotective properties in the L6 skeletal muscle cell line. The effect of arbutin and tertiary butyl hydrogen peroxide (t-BHP) on glucose uptake in cultured L6 cells was investigated by flow cytometry. We also evaluated gene expression levels of GLUT1 and GLUT4 in the L6 cells by quantitative real-time polymerase chain reaction analysis. The results from the study demonstrated that the optimum ROS generation occurred 3 h after 100 µM t-BHP treatment and pretreatment with arbutin (500 and 1000 µM) significantly inhibited the t-BHP induced ROS generation (p < .05). Our result indicated that 3 h pretreatment of L6 cells with 1000 μM of arbutin before 50 μM t-BHP significantly increased glucose uptake than the 50 μM t-BHP alone group (p < .05). Our findings may suggest that an increase in the uptake of 2-NBDG by L6 cells with arbutin pretreatment can be associated with increased expression of GLUT4 and GLUT1 under oxidative stress., (© 2022 John Wiley & Sons Ltd.)

The present study aimed at assessing the effects of exposure to silver nanoparticle (AgNP) and a subsequent acute stress on the expression of various genes involved in the hypothalamus-pituitary-interrenal (HPI) axis in zebrafish, Danio rerio . The fish were exposed to 0 (Control), 0.1 (LC), 0.4 (MC), and 1.2 (HC) mg Ag/L (as AgNP) over a 2-week period, followed by an acute air exposure stress. The whole body cortisol and the expression of selected genes in the fish brain and kidney were analyzed, before and after the acute stress. The results showed that AgNP increased basal cortisol levels and the expression of corticotropin releasing factor, prohormone convertase 1, pro-opiomelanocortin, and melanocortin 2 receptor; however, it suppressed/inhibited whole body cortisol, brain corticotropin releasing factor responses, pro-opiomelanocortin, and the kidney melanocortin 2 receptor responses to the acute stress. AgNP down-regulated the expression of the steroidogenic acute regulatory protein, but it intensified the gene expression in response to the acute stress. Before the acute stress, LC treatment exhibited an up-regulation in Cytochrome P450-11A-1 expression, but MC and HC treatments induced down-regulation. After the acute stress, the AgNP-exposed fish exhibited decreased Cytochrome P450-11A-1 expressions, compared with the Control. Exposure to AgNP significantly increased Cytochrome P450-11B expression. However, after the acute stress, LC treatment exhibited an up-regulation, but MC and HC treatments exhibited down-regulation in the Cytochrome P450-11B gene expression. In conclusion, AgNP suppressed cortisol response to stress, which appears to be a consequence of alterations in the HPI axis at the transcriptomic levels.

The present study tried to measure the formation of melanomacrophage centers (MMCs) in various organs of male and female goldfish exposed to nonylphenol (NP) and aimed to assess its relationship with the main sexual hormones, estrogen receptor expression, and the pigment content of the MMCs. Immature goldfish were exposed to 10 -6 and 10 -7  M NP for 25 days. After obtaining blood for measuring testosterone and estrogen (E2) levels, tissue samples were collected from various organs for histological studies, quantifying pigments using ImageJ software and chemical analysis, and measuring ERα gene expression. Results showed that the order of forming MMCs in various organs exposed to NP was liver > spleen > kidney, and the order of ERα gene expression was liver > testes > spleen > kidney in the male, and liver > spleen > kidney > ovaries in the female. Among the three pigments present in MMCs after exposure to the two doses of NP, melanin was more obvious (especially in the liver) and increased mostly in a dose-dependent manner in both sexes (especially in the male). Chemical analyses confirmed these results. Measurement of testosterone and E2 level in male and female goldfish showed that NP had more effect on the concentration of these hormones in male fish, indicating more endocrine-disrupting potential of NP against the male fish. Generally, the increase of melanin content of melanomacrophage centers coincided with the increase of ERα gene expression and decrease of testosterone level in goldfish after exposure to NP., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Radiodermatitis is the most common complication of radiotherapy. There is no gold standard for managing the radiodermatitis. This study aimed to evaluate the effect of topical Recove ® burn ointment; basically compounded of sesame oil, camphor, and zinc oxide; in preventing acute radiodermatitis., Methods: This double blind RCT (IRCT No.: 201204047136N2) was performed on 71 patients that referred for radiotherapy after mastectomy to Shahid Rajaee Hospital (Babolsar-Iran) during 2013-2017. Patients were allocated into 2 groups; 34 in control group and 37 in Recove ® group. Patients applied the ointment 2 times a day, before every radiation therapy session for 5 weeks. The radiation oncologist assessed the severity of dermatitis weekly for 5 weeks and graded it from 0 to 4 according to the RTOG criteria., Results: Baseline characteristics including age, and BMI had no significant difference between groups. The Recover group patients experienced significantly less severe dermatitis compared to the controls (p<0.001). None of the patients in Recove® group encountered more than grade 2 of RTOG criteria, however, in the control group, 4 (12.9%) patients experienced grade 3 of RTOG and 3 (9.7%) patients developed grade 4 of RTOG at the end of the 5 th week., Conclusion: Our results indicate that Recove ® ointment significantly reduces the severity of acute radiodermatitis., Competing Interests: The compounded natural ointment (Recove®) used in this study was a gift from Tousan Daru Co. as the only domestic provider of the ointment at the time. None of the authors have any financial or job association with Tousan Daru Co. likewise,no funding has been provided by the company for this research project.

The combined effects of copper and polyvinyl chloride (PVC) microparticles were investigated on the metal accumulation, histopathological biomarkers, and targeted transcriptomics in Cyprinus carpio liver. The fish were exposed to 0.25 mg/L copper and/or 0.5 mg/L PVC microparticles over a 14-d period. The results showed that hepatic copper accumulation is facilitated by the PVC microparticles presence in water. All treatments induced significant hepatic stress and inflammation; however, the transcriptional responses involving in detoxification pathways and apoptotic mechanisms were mixed and often down-regulated in the fish exposed to copper and/or PVC microparticles. Exposure to copper and/or PVC microparticles induced hypermeia, leukocyte infiltration and increase in melanomacrophage centers number and area. Generally, the severity of the lesions was in the following order: PVC microparticles < copper < copper+ PVC microparticles. In conclusion, PVC MPs act as a copper vector, facilitating accumulation of copper in the fish liver and increasing the tissue damage., (Copyright © 2022 Elsevier Ltd. All rights reserved.)