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Alzheimer's disease is a neurodegenerative disease that is characterized by the accumulation of two different proteins, β-amyloid and tau. The objective of the present study was to examine the impact of bilateral administration of the cannabinoid receptor antagonist (AM251) in the hippocampus on spatial memory and tau gene expression in an Alzheimer's disease model. The β-amyloid toxin was administered bilaterally into the hippocampus of Wistar male rats to induce Alzheimer's disease. The rats were then divided into four groups: the control group (which received distilled water as a solvent for β-amyloid toxin), the lesion group (which received the β-amyloid), β-amyloid + DMSO group (as antagonist solvent), and the AM251 antagonist receiving groups. During the training course of the Morris water maze test, the antagonist of the cannabinoid 1 receptor antagonist AM251 was administered bilaterally into the hippocampus for four consecutive days at doses of 5, 25, and 100 ng. To evaluate the spatial memory of the animals, the following parameters were analyzed: distance traveled, latency time to reach the hidden platform, velocity of the animals, and tau gene expression in real time. The spatial memory indices were found to be impaired following the injection of β-amyloid and the AM251 cannabinoid antagonist. Following the injection of β-amyloid toxin, there was an increase in mRNA expression of tau protein. However, no significant difference was observed between the cannabinoid antagonist and β-amyloid groups. These results indicate that β-amyloid toxin has a destructive effect on spatial memory and that cannabinoid system plays a positive role in memory formation and consolidation, However, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the effect of a selective A1-adenosine receptor (A1-AR) antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), on the renal dysfunction and histological damage induced by ischaemia/reperfusion at an early stage. Methods: Pentobarbital anaesthetised rats were prepared for measuring renal functional variables. Ischaemia was induced by bilateral renal artery clamping for 30 min followed by a 4 h reperfusion period. In DPCPX-treated rats, it was infused (i.v.) at 10 µg/kg per min before and after renal ischaemia. Both kidneys were examined using light and electron microscopy. Results: The renal ischaemic challenge resulted in major histological and ultrastructural damages, which were associated with decreased creatinine clearance, absolute potassium-excretion and effective free-water reabsorption, but increased fractional sodium-excretion and urine flow during reperfusion period. In DPCPX-treated rats, the histological and ultrastructural damage to the kidneys was improved along with the decrease in creatinine clearance and increase in fractional sodium-excretion being smaller, but the increase in urine flow being larger than those of the non-treated rats, while absolute potassium-excretion and effective free-water reabsorption were equal to those of the sham-operated rats. Conclusion: These findings suggest that endogenous activation of A1-AR contributes to the early development of renal ischaemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Valproic acid (VA) is a broad-spectrum anticonvulsant agent that acts through several molecular mechanisms to control different types of seizures. The main concern of the drug is its liver toxicity. Considering the regulatory roles of the Farnesoid nuclear receptors and the nuclear transcription factor Nrf2 in modifying and neutralizing the harmful effects of oxidative damage, the present study was designed to evaluate the role of FXR-Nrf2 and some downstream target gene alterations in hepatotoxicity induced by VA. Thirty-five eight-week-old male albino mice were randomly divided into five groups, including a control group, and four groups were assigned to receive VA (300 mg/kg/day; oral) for 3, 7, 10, and 14 days. Serum levels of ALT, AST, ALP, and total and direct bilirubin (TB, DB) were measured. Liver histology and the expression of FXR, Nrf2, α-GST, SOD, and TNF-α were assessed using H&E staining and real-time RT-PCR techniques. Maximum extent of biochemical and histopathological damage was observed on the 14th day, but changes in the expression of FXR, Nrf2, α-GST, and SOD were seen at three points: a significant upregulation on the 3rd day, a remarkable downregulation on the 10th day, and a second-time upregulation on the 14th day. In conclusion, considering the observed dysregulation in FXR-Nrf2 cascade expression during VA administration, it seems that downregulation in this pathway and consequently its downstream detoxification and antioxidant genes may play a role in liver toxicity.

Endoscopic retrograde cholangiopancreatography is a complex procedure with a significant risk of severe consequences. We herein report a 56-year-old Middle Eastern female who was diagnosed with acute ascending cholangitis. Endoscopic retrograde cholangiopancreatography was performed with gallstone absorption and stent implanting. However, the patient developed significant pneumothorax; pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and subcutaneous emphysema of the abdomen, chest, right arm and shoulder, face and right orbital area. Radiological studies demonstrated no evidence of perforation on bowel obstruction. The patient was treated successfully with good results and post-operative follow-up was unremarkable. In conclusion, air leakage following endoscopic retrograde cholangiopancreatography without evidence of perforation is extremely rare. While pneumothorax development usually requires thoracostomy; pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and subcutaneous emphysema are usually treated conservatively., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Post-intubation tracheal rupture (PiTR) is an extremely uncommon disorder. Pneumothorax, pneumomediastinum, hemorrhage, cutaneous emphysema, and sepsis are common clinical presentations that eventually result in organ failure and mediastinitis. Endoscopy and computed tomography (CT) are considered the gold standards for assessment and diagnosis., Case Presentation: Here, the authors present a 96-year-old woman with asthma and ischemic heart disease presented to the Emergency Department with dyspnea following viral pneumonia. Despite initial treatment, her condition worsened, requiring tracheal intubation. Subsequent complications led to a diagnosis of tracheal rupture, requiring surgical repair. The procedure involved using a muscle graft from the Latissimus Dorsi muscle: which is a novel Surgical Technique as the authors have conducted a literature review., Discussion: Upon scrutinizing analogous cases delineated within the medical literature, it becomes evident that our patient manifests four distinct risk factors. These factors include gender, advanced age, asthma, and prolonged steroid use.While the clinical manifestation and diagnostic methods for tracheal rupture are frequently consistent throughout cases, there is a significant variation in the surgical treatments used to treat the condition., Conclusion: More research should be conducted to investigate the use of muscle grafts as a treatment technique for tracheal rupture in the future., Competing Interests: The author declares no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The present study aimed to investigate the effects of fish oil supplements compared to corn oil on serum lipid profiles by performing a meta-analysis of randomized controlled trials (RCTs)., Methods: Online databases including PubMed, Web of Science, and Scopus were searched until 30 December 2022. Pooled effect sizes were reported as the weighted mean difference (WMD) with 95% confidence intervals (CI). The Cochrane Collaboration's risk-of-bias tool was utilized to evaluate the quality of the studies. Lipid parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL), were assessed in the meta-analysis., Results: Overall, 16 eligible trials were included in this systematic review and meta-analysis. The results revealed that the fish oil supplements significantly reduced TG (WMD: - 25.50 mg/dl, 95% CI: - 42.44, - 8.57, P = 0.000) levels compared to corn oil. Also, in this study, fish oil supplements had a positive and significant effect on HDL (WMD: 2.54 mg/dl, 95% CI: 0.55, 4.52). There were no significant changes in TC and LDL., Conclusions: Our findings showed the effects of fish oil supplements on reducing TG and increasing HDL-c compared to corn oil. Further larger and well-designed RCTs are required to confirm these data., (© 2024. The Author(s).)

Exposure to aflatoxin B1 can be associated with reproductive toxicity, accompanied by decreased sperm concentration in animal models. The aim of this meta-analysis was to determine the correlation between aflatoxin B1 exposure and sperm concentrations of male rodents (both mice and rats). According to inclusion and exclusion criteria, 8 articles were selected to assess in the current meta-analysis. The random effects and pooled analysis indicated that sperm concentration was decreased in mice [MD sperm = -20.79×10 6 /sperm/g testis (95%CI =-1.3 to -50.5)] and in rats [-24.34×10 6 /sperm/g testis (95%CI: -7.60 to -44.35)] after exposure to aflatoxin B1 compared with control groups. A significant heterogeneity was found among studies (for mice I 2 =99.7%, %, P <0.000 and rats =I 2 =98.8, P <0.000). The findings of present meta-analysis showed the association between aflatoxin B1 exposure and a decrease in sperm concentration in rodents.

Introduction: Farnesoid-X-activated receptor (FXR) is considered as an upstream controller which could influence the other key regulatory genes encoding cellular antioxidant defense system., Methods: Thirty-five male Wistar rats (240 ± 20 g) were randomly allocated into five groups: 1) control, 2) received gentamicin (100 mg/kg/d) for three days (GM-3d), 3) seven days (GM-7d), 4) 10 days (GM-10d), and 5) 14 consecutive days (GM-14d). Biochemical measurements of BUN and serum creatinine (SCr), histological assessment of renal samples as well as molecular analysis using real-time qRT-PCR were used to investigate the pattern of changes in different levels., Results: Administration of gentamicin was associated with a significant increase in the BUN and SCr until the 10th day, which then suddenly dropped at the day 14. Meantime, the maximum histological distortion was also seen on the 10th day but in a similar pattern, 14th day was associated with clear improvement. Compared to the control value, the maximum reduction in the mRNA expression of Farnesoid X-activated receptor (FXR), nuclear factor erythroid 2-related factor 2 (Nrf2) and Glutathione cysteine ligase-modulatory subunit (GCLM), occurred at the 3rd and 7th days, respectively. Compared to the control, the mRNA expression of the mentioned genes significantly increased up to day 14. Apart from the 3rd day, the mRNA expression of alpha-glutathione S-transferase (α-GST) and superoxide dismutase (SOD) showed a similar descending and ascending pattern at 7th and 10th days, respectively., Conclusion: The expression of FXR, as an upstream controller gene and its downstream pathways mediated by Nrf2, could play a role in gentamicin-induced nephrotoxicity but the pattern of expression was rather biphasic at the acute phase or the subacute ones.  DOI: 10.52547/ijkd.7523.

Objectives: Gentamicin-induced nephrotoxicity was used as an experimental model of kidney disease. The present study was performed to assess the therapeutic role of cannabidiol (CBD) against gentamicin-induced renal damage., Materials and Methods: Forty two male Wistar rats were randomly allocated into 6 groups (n=7), including: (1) Control, (2) Vehicle, (3) Gentamicin-treated group (100 mg/kg/day) for 10 days (GM), (4-6) 3 Gentamicin-CBD-treated groups (2.5, 5, and 10 mg/kg/day) for 10 days (GM+CBD2.5, GM+CBD5, GM+CBD10). Serum levels of BUN and Cr, renal histology as well as real-time qRT-PCR were used to investigate the pattern of changes at different levels., Results: Gentamicin increased serum BUN and Cr ( P <0.001), down-regulation of FXR ( P <0.001), SOD ( P <0.05) and up-regulation of CB1 receptor mRNA ( P <0.01). Compared to the control group, CBD at 5 decreased ( P <0.05) and at 10 mg/kg/day increased the expression of FXR ( P <0.05). Nrf2 expression in CBD groups was increased ( P <0.001 vs. GM). The expression of TNF-α compared to the control and GM groups, was significantly increased in CBD2.5 ( P <0.01) and CBD10 ( P <0.05). Compared to the control, CBD at 2.5 ( P <0.01), 5 ( P <0.001) and 10 ( P <0.001) mg/kg/day significantly increased the expression of CB1R. Up-regulation of CB1R in the GM+CBD5, was significantly higher ( P <0.05) than the GM group. Compared to the control group, the most significant increase in CB2 receptor expression was observed at CBD10 ( P <0.05)., Conclusion: CBD particularly at 10 mg/kg/day might be of significant therapeutic benefit against such renal complications. Activating the FXR/Nrf2 pathway and counteracting the deleterious effects of CB1 receptors via CB2 receptors scale-up could be part of the protective mechanisms of CBD., Competing Interests: The authors declare that they have no conflicts of interest.

Renin-angiotensin system (RAS) components such as angiotensin II, angiotensin receptors (AT 1 R and AT 2 R), and angiotensin-converting enzyme (ACE) are expressed in different cell types of the skin. Through AT1R, angiotensin II increases proinflammatory cytokines contributing to fibrosis, angiogenesis, proliferation, and migration of immune cells to the skin. In contrast, AT 2 R suppresses the effects mentioned above. Many studies show that angiotensin receptor blockers (ARBs) and angiotensin-converting enzymes (ACEi) reduce the proinflammatory cytokines and fibrogenic factors including transforming growth factor β (TGF-β), Connective tissue growth factor (CTGF), and IL-6. This review article provides a detailed research study on the implications of ARBs in wound healing, hypertrophic scar, and keloids. We further discuss the therapeutic potentials of ARBs in autoimmune and autoinflammatory skin diseases and cancer, given their anti-fibrotic and anti-inflammatory effects., Competing Interests: The authors declare that there are no conflicts of interest.

Kiwi extract (KE) including different components such as quercetin, vitamins C and E, and actinides has been known as a debridement agent for burn wounds. In this study, electrospun poly(ɛ-caprolactone)/cellulose acetate blend nanofibers incorporating KE (PCL/CA/KE) were prepared and their performance was evaluated for healing acceleration of burn wounds. The physicochemical characterization of PCL/CA/KE nanofibers showed an average diameter of ∼420 nm, porosity of 70%, water contact angle of 61°, and water uptake of ∼220%. Moreover, the continuous release trend of KE from PCL/CA blend nanofibers happened during 24 h and the release mechanism was governed by the Fickian diffusion. Besides the cytocompatibility of PCL/CA/KE nanofibers, their in vivo experiments revealed that the bioactive wound dressing based on the sample has higher wound closure compared to KE after 21 days. Histopathology of wounds dressed by PCL/CA/KE nanofibers indicated epidermal formation along with a fully extended layer. Eventually, the obtained results confirmed that the PCL/CA/KE nanofibrous sample was a promising wound dressing for burn wound healing.

Anesthesia and analgesia are major components of many interventional studies on laboratory animals. However, various studies have shown improper reporting or use of anesthetics/analgesics in research proposals and published articles. In many cases, it seems "anesthesia" and "analgesia" are used interchangeably, while they are referring to two different concepts. Not only this is an unethical practice, but also it may be one of the reasons for the proven suboptimal quality of many animal researches. This is a widespread problem among investigations on various species of animals. However, it could be imagined that it may be more prevalent for the most common species of laboratory animals, such as the laboratory mice. In this review, proper anesthetic/analgesic methods for routine procedures on laboratory mice are discussed. We considered the available literature and critically reviewed their anesthetic/analgesic methods. Detailed dosing and pharmacological information for the relevant drugs are provided and some of the drugs' side effects are discussed. This paper provides the necessary data for an informed choice of anesthetic/analgesic methods in some routine procedures on laboratory mice., (© 2022. The Author(s).)

Objectives: This investigation aims to evaluate the association between the concentration of cell-free DNA (cfDNA) in the spent culture medium (SCM) with implantation rate and the maternal immune system in the invitro fertilization (IVF). In this study, 30 embryos were cultured and scored according to Gardner's criteria. SCM was gathered on day five from every embryo to analyze the quantity of cfDNA. The real-time PCR technique evaluated the expression level of transcription factors, including Foxp3, RORγt, GATA3, and T-bet. The percentage of Th1, Th2, Th17, Treg, NK cells, and NK cells cytotoxicity was evaluated by flow cytometry., Results: The concentration of cfDNA in the β-HCG (-), β-HCG ( +), and ongoing pregnancy groups were 20.70 ± 9.224 ng/µL, 27.97 ± 7.990 ng/µL, and 28.91 ± 8.566 ng/µL, respectively. The ratio of Th1/Th2 and Th17/Treg reduced significantly in pregnant women, as well as the level of NK cells and NK cytotoxicity cells fell dramatically in the ongoing pregnancy group. The expression level of RORγt and T-bet declined while the expression level of Foxp3 and GATA3 increased considerably in pregnant mothers. Our investigation revealed that the concentration level of cfDNA in SCM could not be associated with implantation rate, prediction of ongoing pregnancy, and maternal immune system., (© 2022. The Author(s).)

Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis., Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β 1 -adrenergic receptors (β 1 -AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05., Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β 1 -AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β 1 -AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE., Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions., (Copyright: © Iranian Journal of Medical Sciences.)

Objectives: This study aimed to evaluate the relationship between Farnesoid-X-activated receptors (FXR) as nuclear regulators of the antioxidant defense system as well as cardiac mitochondrial carrier proteins of UCP2 and UCP3 in cardiac damage induced by cirrhosis., Materials and Methods: Twenty-two male Wistar rats (200-250 g) were randomly divided into 3 experimental groups, including a control group (n=6), a sham-operated group (n=8), and a bile duct ligated (BDL) group (n=8). Four weeks after surgical intervention, biochemical assessment (AST, ALT, GGT, LDH, and ALP), histological observation, and molecular evaluation (FXR, UCP2, UCP3, BNP, Caspase3, and GAPDH) using real-time RT-PCR were performed., Results: Compared with the sham-operation group, the BDL group showed a significant rise in liver enzymes of AST, ALT, GGT, LDH, and ALP. Defined fibrotic and necrotic bundles and thick reticulin fibers were also found in BDL liver tissue. Besides liver morphological alterations, left ventricles of BDL ones were also associated with defined cardiomyocyte hypertrophy, myofiber vacuolization, and clear pigmentation. Findings showed a significant up-regulation of cardiac Brain Natriuretic Peptide (BNP) along with marked down-regulation in hepatic FXR, cardiac FXR, and cardiac UCP2 and UCP3. However, the expression of caspase 3 in the cardiac tissue was not affected by BDL operation during 4 weeks., Conclusion: Expression of FXR as an upstream regulator of cellular redox status, besides the non-enzymatic ROS buffering defense system of cardiac UCPs, has a pivotal role in the pathogenesis of cirrhotic-induced cardiac abnormality in rats., Competing Interests: The authors state no conflicts of interest.

Objectives: In the present study, we aimed to determine whether intraperitoneal injection of platelet-rich plasma (PRP) could have a neuroprotective effect on learning, memory, and synaptic plasticity impairment as well as hippocampal apoptosis in rats with hepatic encephalopathy induced by bile duct ligated (BDL)., Methods: The rats were divided into four groups: the control, sham, BDL+ V (vehicle), and BDL+ PRP. The BDL rats were treated with PRP immediately after the surgery, and the injection was done every 3 days for 30 days. The passive avoidance and Morris water maze tests were used for the evaluation of learning and memory. The long-term potentiation (LTP), basal-synaptic transmission, and paired-pulse ratio, as an index for measurement of neurotransmitter release probability, were evaluated by field-potential recording. After taking a blood sample for assessment of the liver enzymes, the animals were sacrificed and their hippocampus was removed for evaluation of cleaved caspase-3 by Western blot., Results: Serological assessment of the liver function showed that BDL severely impaired the liver function. Also, PRP treatment could partially improve the liver dysfunction along with recovery in fear memory and spatial learning memory performance, LTP, basal-synaptic transmission, and neurotransmitter release probability. PRP-treated rats also showed a significant reduction in neuronal apoptosis in the CA1 area., Conclusions: The results of this study suggest that PRP improves cognitive performance and synaptic plasticity in BDL rats via direct neuroprotective property and/or indirectly by improvement of hepatic dysfunction., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: The most important toxicity of acetaminophen is hepatotoxicity. Farnesoid X-activated receptors ( FXR ) are one of the nuclear receptor superfamily members which have a pivotal role in the bile acid regulation. The objective of the present study was to examine the role of FXR in mediating the hepatoprotective effects of saffron., Methods: Male Wister rats were randomly allocated into five groups including a control, vehicle, acetaminophen and two saffron extract groups of 150 and 300 mg/kg/day. The liver function and hepatic FXR expression were evaluated using biochemical assay and real time RT-PCR, respectively. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test., Results: Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) of the acetaminophen group were significantly higher than the control group whereas those of the extract-treated groups were significantly lower than those of the acetaminophen group. The real time RT-PCR findings showed a non-significant down-regulation of FXR mRNA expression, however, a dose-dependent FXR up-regulation was seen in the groups treated with 150 and 300 mg/kg of the extract for 2.67 (p=0.002) and 10.22 (p=0.0001) fold, respectively., Conclusion: The main finding of the present study was that the hepatic FXR up-regulation had an important role in saffron hepatoprotective activity., Competing Interests: The authors have declared that there is no conflict of interest.

Rationale and Objective: Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting effects of EE and VitD can co-occur., Methods: Aged rats were housed for 6 weeks in one of three housing conditions: environmentally enriched (EE), socially enriched (SE), or standard condition (SC). Further, a 4th group was co-treated with VitD supplementation (400 IU kg -1 daily, 6 weeks) under EE conditions (EE + VitD)., Results: Treatment with VitD and EE housing were associated with higher score on measures of learning and memory and exhibited lower anxiety scores compared to EE alone, SE or SC as assayed in the elevated plus maze, Morris water maze, passive avoidance, and open field tasks. Additionally, in the EE + VitD group, mRNA expression levels of NGF, TrkA, BDNF, Nrf2, and IGF-1 were significantly higher compared to expression seen in the EE group. Furthermore, field potential recordings showed that EE + VitD resulted in a greater enhancement of hippocampal LTP and neuronal excitability when compared to EE alone., Conclusions: These findings demonstrate that in aged rats exposure to EE and VitD results in effects on hippocampal cognitive dysfunction and molecular mechanisms which are greater than effects of EE alone, suggesting potential for synergistic therapeutic effects for management of age-related cognitive decline., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Farnesoid-X-activated receptors (FXR) are key modulators of liver regeneration. Milk thistle and Chicory are known as potent protective remedies in several liver disorders. The objective of this work was to examine the role of FXR in the hepato-healing properties of milk thistle (MTE) and chicory extracts (CE) in a rat model of acetaminophen-induced hepatotoxicity., Materials and Methods: Male Wistar rats were randomly divided into seven groups including control, vehicle, acetaminophen (500 mg/kg/day, oral), acetaminophen plus oral MTE 200 and 400 mg/kg/day, and acetaminophen plus oral CE 500 and 1000 /kg/day for 28 days. Liver function and histology as well as the pattern of hepatic FXR expression were assessed after 4 weeks., Results: Administration of acetaminophen was associated with a significant elevation of liver transaminase along with the architectural injuries. In contrast, chronic concomitant administration of both MTE and CE significantly restored the liver function and structural abnormality. The main molecular findings of the study revealed that the lower doses of both MTE and CE led to a marked upregulation of hepatic FXR expression., Conclusion: Discovery of the involvement of the nuclear modulating pathways in hepatoprotective activity of the extracts, providesa new mechanistic insight which needs further investigations., Competing Interests: The authors have declared that there is no conflict of interest.

Competing Interests: Conflict of Interest: None declared.

Background: Liposomes constitute a promising drug delivery vehicle, and are believed to improve drugs' effectiveness. This study was aimed to compare antihypertensive and vascular modifying activities of liposomal and non-liposomal forms of ascorbic acid., Methods: Forty-nine male Sprague-Dawley rats were randomly divided into seven groups (n=7): A sham vehicle-receiving (Sham-veh), hypertensive (HTN), vehicle-receiving hypertensive (HTN-Veh), two liposomal Ascorbic acid-treated hypertensive at 50 or 100 mg/kg/day (LVC-50 and LVC-100), and two non-liposomal Ascorbic acid-treated hypertensive at 50 or 100 mg/kg/day (VC-50 and VC-100). Systolic blood pressure (SBP) and heart rate (HR) were measured weekly; after 4 weeks, dose-responses to phenylephrine (PE) in the absence and presence of nitro-L-arginine methyl ester (L-NAME), acetylcholine (Ach), and sodium nitroprusside (SNP) were obtained on aortic rings. Data were analyzed with one-way ANOVA and Duncan's multiple range test at a P value of <0.05 using Sigmastat statistical software., Results: Compared to the non-liposomal form, the liposomal one was associated with more prominent effects on the final SBP. Both forms of Ascorbic acid decreased SBP dose-dependently. The basal and stimulated release of Nitric Oxide (NO) was significantly recovered by both forms of Ascorbic acid. The PE maximal responses were not significantly different between the liposomal and non-liposomal groups (P=0.08). Although the Emax of Ach-relaxation response was not different in two preparation forms, Ach-relaxation response induced a lower concentration of the liposomal form of Ascorbic acid (P=0.03., Conclusion: The liposomal Ascorbic acid exhibited relaxation activity in significantly lower concentrations. The observed effects were partly mediated by the increased basal release of NO., (Copyright: © Shiraz University of Medical Sciences.)

Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in β-thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in β-thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in β-thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti-oxidants. AF in β-thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron-induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies., (© 2018 Wiley Periodicals, Inc.)

Background: Celiac disease (CD) is known as a reason of metabolic osteopathy. Progression of non-invasive methods such as bone densitometry has shown that an important ratio of CD cases is faced with impaired bone mass and such cases are prone to bone fractures. Variety of low bone mineral density in CD is probably because of ignored confounding factors such as age, menopause, and drug. The aim of our study was to systematically review the osteoporosis and osteopenia incidences among premenopausal females and males with CD., Methods: This systematic review was done based on preferred reporting items for systematic reviews (PRISMA) guidelines. PubMed and Scopus and Cochran databases were searched according to the relevant medical subject headings (MeSH) of CD and bone mineral density until 2018. Prevalence of osteopenia and osteoporosis were used as effect size for meta-analysis. Cochrane Q (p < 0.05) and I 2 index were presented to reveal the heterogeneity., Results: 54 eligible full text reviews were included and nineteen selected for data extraction. Eleven articles didn't have our inclusion criteria and had ignored confounding factors like age and menopause, and we excluded; data extraction was done in eight studies. A total of 563 premenopausal women and men who were from, UK, Brazil, India, Hungary, and Poland were included. The pooled prevalence of osteoporosis was 14.4% [95%CI: 9-20.5%] (Cochrane Q = 7.889, p = 0.96, I 2  = 49.29%), and osteopenia was 39.6% [31.1-48.8%] (Cochrane Q = 14.24, p = 0.07, I 2  = 71.92%), respectively., Conclusion: Our findings suggest that bone loss is more prevalent in celiac disease and can be associated with increased risk of fracture. However, but results are pooled prevalence and we need more case -control studies with more sample size and consideration of confounding factors.

Background: Several lines of evidence revealed that chronic treatment of anabolic androgenic steroids (AASs) is accompanied with some cardiovascular side effects and in addition they also negatively mask the beneficial effects of exercise training on cardiac performance., Methods: The present study examined whether the nandrolone decanoate (ND)-induced cardiac effects were mediated by changing the cardiac uncoupling protein 2 (UCP2) and 3 (UCP3) expression. Five groups of male wistar-albino rats including sedentary control (SC), sedentary vehicle (SV), sedentary nandrolone decanoate (SND), exercise control (EC), and exercise nandrolone decanoate (END) were used. ND was injected (10 mg/kg/week, intramuscular) to the animals in the SND and END groups and endurance exercise training was performed on a treadmill five times per week., Results: The protein expressions of cardiac UCP2 and UCP3 have significantly increased in both the SND and EC groups compared to the SC ones. In contrast to UCP3, no significant differences were found between UCP2 protein expressions of the END and SC groups. Compared with the SND group, the exercise training significantly decreased the UCP2 and UCP3 protein expressions in the END group., Conclusions: The study has indicated that endurance exercise in combination with ND can result in that the exercise effectively antagonizes the effects of ND treatment on UCP2 and UCP3 up-regulation.

Salt rejection phenomenon was investigated using armchair silicon carbide (SiC) nanotubes under applied electric fields. The systems included the (7,7) and (8,8) SiC nanotubes surrounded by silicon nitride membrane immersed in a 0.4mol/L aqueous solution of sodium chloride. Results of molecular dynamics (MD) simulations for selective separation of Na + and Cl - ions showed that the (7,7) SiC nanotube is suitable for separation of cations and the (8,8) SiC nanotube can be used for separating anions. The water desalination by SiC nanotubes was demonstrated by potential of mean force for Na + and Cl - ions in each SiC nanotube. Furthermore, the ionic current, ion residence time, and the radial distribution functions of species were measured to evaluate the properties of the system. Based on the results of this research, the studied SiC nanotubes can be recommended as a nanostructure model for water desalination., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Multiple Sclerosis (MS) is defined as one of the inflammatory autoimmune disorders and is common. Its exact etiology is unclear. There are some evidences on the role of environmental factors in susceptible genetics. The aim of this study is to evaluate the possible role of Selenium, Zinc, Copper, Lead and Magnesium metals in Multiple Sclerosis patients., Methods: In the present analytical cross-sectional study, 56 individuals including 26 patients and 30 healthy controls were enrolled in the evaluation. The serum level of Se, Zn, Cu, Pb were quantified in graphite furnace conditions and flame conditions by utilizing an atomic absorption Perkin Elmer spectrophotometer 3030. The serum levels of Mg were measured by auto analyzer 1500 BT. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls by using independent-samples t-test for normal distribution and Mann-Whitney U test as a non-parametric test. All statistical analyses were carried out using SPSS 11.0., Results: As well as the Zn, Cu, and Se, there was no significant difference between MS patients and healthy individuals in Pb concentrations (p-value = 0.11, 0.14, 0.32, 0.20 respectively) but the level of Mg was significantly different (p= 0.001)., Conclusion: All serum concentrations of Zn, Pb, Se, Cu in both groups were in normal ranges and there was no difference in MS patients compared with the healthy group who were matched in genetics. Blood level of Mg was significantly lower in MS patients. But it should be noted that even with the low level of serum magnesium in MS patients, this value is still in the normal range., Competing Interests: There is no conflict of interest to be declared.

ATP-sensitive potassium channels are supposed to have a substantial role in improvement of cardiac performance. This study was performed to evaluate whether nandrolone decanoate (ND) and (or) exercise training could affect the expression of cardiac K(ATP) channel subunits. Thirty-five male albino Wistar rats were randomly divided into 5 groups, including sedentary control (SC), sedentary vehicle (SV), sedentary ND (SND), exercise control (EC), and exercise and ND (E+ND). Exercise training was performed on a treadmill 5 times per week. ND was injected (10 mg/kg/week, i.m.) to the rats in the SND and E+ND groups. Following cardiac isolation, the expression of both sarcolemmal and mitochondrial subunits of K(ATP) channel was measured using Western blot method. The expression of sarcolemmal, but not mitochondrial, subunits of K(ATP) channel (Kir6.2 and SUR2) of EC group was significantly higher compared with SC group while ND administration (SND group) did not show any change in their expression. In the E+ND group, ND administration led to decrease of the over-expression of sarcolemmal Kir6.2 and SUR2 which was previously induced by exercise. There was no significant association between the mitochondrial expression of either Kir6.2 or SUR2 proteins and administration of ND or exercise. Supra-physiological dosage of ND negatively reverses the effects of exercise on the cardiac muscle expression of sarcolemmal, but not mitochondrial, K(ATP) channel subunits.

Background and Aims: The aim of this study was to investigate the early changes of cardiac uncoupling protein-2 (UCP2) expression following myocardial ischemia reperfusion in rats chronically treated with ramiprilat and losartan., Methods: Male Wistar rats were assigned into seven groups (six in each): intact (control); sham-operated; nontreated rats subjected to ischemia and reperfusion (IR); ramiprilat-treated rats with (Ram+IR) and without ischemia (Ram); losartan treated with (Los+IR) and without ischemia (Los). Quantitative evaluation of UCP2 mRNA was carried out using real-time reverse transcription-polymerase chain reaction (RT-PCR). Mitochondria were isolated, and protein expression was quantified by Western blotting., Results: In IR group: UCP2 protein but not mRNA level was increased in the ischemic area of the left ventricle (LV) (172% ± 26.7, p < 0.001 vs. LV of control). Following acute myocardial IR, UCP2 protein levels was increased in the ischemic area of the LV but not in RV, suggesting the local effect of ischemia on UCP2 expression. IR-induced overexpression of UCP2 was suppressed by ramiprilat and losartan., Conclusion: These findings suggest that losartan and ramiprilat can suppress UCP2 expression following myocardial IR, and by this mechanism may protect the myocardium against IR injury., (© The Author(s) 2013.)

Aims: We aimed to evaluate the transcription and translation of genes for uncoupling protein 2 (UCP2) & uncoupling protein 3 (UCP3) in rat heart mitochondria of both ventricles after myocardial ischemia followed by various periods of reperfusion., Main Methods: Seven groups of 8 male Wistar rats were evaluated for the effects of ischemia and also reperfusion, using Western blot of isolated mitochondrial proteins in addition to RNA extraction followed by real-time RT-PCR analysis., Key Findings: In rats with 30 min of reperfusion (R30) UCP2 protein was increased 213±33%, which is meaningfully more than the control group (P<0.001). Western blot showed increase in UCP2 protein level in groups receiving reperfusion for 60 min (R60), 120 min (R120) and 180 min (R180) as much as 152±28% (P<0.001 vs. control), 123±19% (P<0.01 vs. control) and 131±30% (P<0.01 vs. control), respectively. There was no statistically important difference in UCP2 mRNA between either right or left ventricles of ischemic and ischemia-reperfusion (IR) groups vs. control group. In the groups R180 and R240, UCP3 protein levels showed 131±27% and 102±18% increase, respectively (both P<0.001 vs. control group). However, the change in UCP3 level in other groups was not significantly different from the control group., Significance: UCP2 and UCP3 protein levels are considerably increased in the ischemic area early after acute myocardial IR. The right ventricular UCP2 protein expression does not change, that is, effect of IR on UCP2 protein is a local process. However, UCP3 protein level increased both in ischemic area of the left ventricle and in non-ischemic area of the right ventricle., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: HYPOTHESIS/INTRODUCTION: Our aim was to investigate whether a non-hypotensive dose of ramiprilat and losartan has myocardial protective effects during myocardial ischemia/reperfusion in vivo., Materials and Methods: Three groups of rats were given 10 mg/kg per day of losartan for one (L-1W), four (L-4W) or 10 (L-10W) weeks. Another three groups were given 50 µg/kg per day of ramiprilat for one (R-1W), four (R-4W) or 10 (R-10W) weeks. The animals underwent 30 min of left anterior descending artery occlusion and subsequent reperfusion for 120 min., Results: Myocardial infarct size (IS) was reduced in R-1W (28.4 ± 6.3%, p < 0.001), R-4W (27.8 ± 7.4, p < 0.001), L-4W (31.8 ± 6%, p < 0.05) and L-10W (25.3 ± 5.7, p < 0.001) groups compared with a saline group (48.3 ± 7.8%). A significant reduction in the number of ventricular ectopic beats (VEBs) was noted in groups R-1W (209 ± 41, p < 0.01), R-4W (176 ± 39, p < 0.01), L-4W (215 ± 52, p < 0.05) and L-10W (191 ± 61, p < 0.01 vs. saline 329 ± 48). The incidence of irreversible ventricular fibrillation (VF) and mortality were decreased significantly only in L-10W group. There were no significant decreases in episodes of VT, the incidence of irreversible VF and mortality in all of the groups treated with ramiprilat., Conclusion: These data indicate that losartan and ramiprilat protect the heart against ischemia/reperfusion injury independently of their hemodynamic effects but in a time-dependent manner.