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Since the middle of the twentieth century, the use of dyes has become more common in every food group as well as in the pharmaceutical, textile and cosmetic industries. Azo dyes, including carmoisine, are the most important of the dye classes with the widest color range. In this study, the effects of carmoisine exposure on the embryonic development of zebrafish at a wide dose scale, including recommended and overexposure doses (from 4 to 2000 ppm), were investigated in detail. For this purpose, many morphological and physiological parameters were examined in zebrafish exposed to carmoisine at determined doses for 96 h, and the mechanisms of action of the changes in these parameters were tried to be clarified with the metabolite levels determined. The no observed effect concentration (NOEC) and median lethal concentration (LC

Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

Silver nanoparticles (AgNPs) are prominent nanomaterials that are efficiently used in different industries including medical products, water treatment, and cosmetics. However, AgNPs are known to cause adverse effects on the ecosystem and human health. In this study, aqueous extract of Rumex patientia (RP) was used as a reducing and stabilizing agent in AgNP biosynthesis. The obtained activated carbon (AC) from Chenopodium album (CA) plant was combined with RP-AgNPs to synthesize RP-Ag/AC NPs. Next, the effects of these green synthesis RP-Ag/AC NPs on zebrafish (Danio rerio) embryos and larvae were investigated. First, we characterized the RP-Ag/AC NPs by using X-ray diffraction (XRD) and transmission electron microscopy (TEM) and determined LC50 value as 217.23 mg/L at 96 h. Next, the alterations in survival rate, hatching rate, and morphology of the larvae at 96 h were monitored. The survival rates decreased in a dose-dependent manner. Morphological defects such as yolk sac edema, pericardial edema, spinal curvature, and tail malformation in the NP-treated larvae were observed. RP-Ag/AC NPs stimulated the production of neuronal NOS (nNOS) and 8-OHdG in zebrafish brain tissues in a dose-dependent manner and enhanced neutrophil degeneration and necrosis at concentrations of 50 and 100 mg/L. Thus, the obtained data suggest that the green synthesis process is not sufficient to reduce the effect of oxidative stress caused by AgNPs on oxidative signaling.

This study was conducted to assess the impacts of prolonged fasting (70 and 120days) on the morphological, biochemical, oxidative stress responses, immune-related gene expression, histopathology, and DNA damage in rainbow trout. Final weight (FW), hepatosomatic index (HSI), and condition factor (CF) significantly decreased in both 70 and 120days of fasting compared to the pre-fasting group (p p p

Anxiety and obesity are two current phenomena. They are among the important public health problems with increasing prevalence worldwide. Although it is claimed that there are strong relations between them, the mechanism of this relationship has not been fully clarified yet. On the other hand, the effect of this relationship on the offspring has been another research subject. In this study, obese zebrafish were obtained by feeding two different diets, one containing high amount of lipid (HF) and the other containing high amount of carbohydrate (HK), and their anxiety levels were evaluated. To establish a relationship between these two phenomena, in addition to histopathological and immunohistochemical analysis in the brain tissues of fish, the transcription levels of some genes related to lipid and carbohydrate metabolisms were determined. In addition, offspring were taken from obese zebrafish and studied to examine the effect of parental obesity on offspring. As a result, it was observed that the HC diet, causing more weight increase than the HF diet, showed an anxiolytic while the HF diet an anxiogenic effect. It was suggested that the probable cause of this situation may be the regulatory effect on the appetite-related genes depending on the upregulation severity of the PPAR gene family based on the diet content. In addition, it was also suggested that it may have contributed to this process in neuron degenerations caused by oxidative stress. Regarding effects on offspring, it can be concluded that HF diet-induced obesity has more negative effects on the next generation than the HC diet. Level of evidence No Level of evidence: animal study.

In the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO2, SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.

Cyclophosphamide (CYP) is a chemotherapeutic agent used in the treatment of autoimmune disorders and malignant diseases. However, its usage is restricted due to its severe side effects, especially hepatotoxicity and nephrotoxicity. This study aimed to investigate the protective role of chrysin (CH) against CYP-induced hepatotoxicity and nephrotoxicity in rats. In the present study, 35 male Wistar rats were randomly divided into 5 groups with each group consisting of 7 rats. The rats were pretreated with CH orally in doses of 25- and 50-mg/kg body weight for 7 consecutive days, and CYP (200-mg/kg body weight, i.p.) was administrated on the 7th day 1 h after the last dose of CH. It was found that CH could ameliorate CYP-induced elevations of ALT, ALP, AST, urea, creatinine, MDA, and hepatorenal deterioration, and enhance antioxidant enzymes' activities such as SOD, CAT, and GPx, and GSH's level. Furthermore, CH reversed the changes in levels of inflammatory, apoptotic, and autophagic parameters such as NF-κB, TNF-α, IL-1β, IL-6, iNOS, COX-2, Bax, Bcl-2, and LC3B in liver and kidney tissues. To conclude, the findings of this study demonstrated that CH has a protective effect against CYP-induced hepatorenal toxicity.

Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress. In this regard, it is important to protect cells against damage by inducing antioxidant response. Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion. Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group (14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue. Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renal injury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-alpha levels besides the 8-OHdG formation were downregulated. According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries.

This study was carried out to determine the protective effects of lithium borate (LTB) on blood parameters and histopathological findings in experimentally induced acute cadmium (Cd) toxicity in rats. Twenty-eight male Wistar albino rats were used, weighing 200-220 g, and they were randomly divided into four groups, including one control and the following three experimental groups: a Cd group (0.025 mmol/kg), a LTB group (15 mg/kg/day orally for 5 days), and a LTB + Cd group (15 mg/kg/day orally for 5 days and Cd 0.025 mmol/kg by intraperitoneal injection on the fifth day). All the rats in the study were anesthetized with ketamine at the end of the sixth day, blood was taken from their hearts, and then the rats were decapitated. The values in the control and LTB group were usually close to each other. White blood cell (WBC), neutrophil %, and C-reactive protein (CRP) levels increased in the Cd and LTB + Cd groups while lymphocyte and monocyte levels decreased in a statistically significant manner, in comparison to the other groups. It was determined that the levels of red blood cells (RBCs), hematocrit (Htc), and hemoglobin (Hb) did not change in the groups. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the Cd and LTB + Cd groups significantly increased, in comparison to the other groups, while the glucose, alkaline phosphatase (ALP), albumin (ALB), and total protein (TP) levels decreased. According to histopathological findings in the control and LTB groups, the liver and kidney tissues were found to have normal histological structures. In the Cd group, severe necrotic hemorrhagic hepatitis, mild steatosis, and mononuclear cell infiltration were detected in the liver. In the LTB + Cd group, degeneration and mild mononuclear cell infiltration were found in the liver. Regarding the kidney tissue in the Cd group, severe intertubular hyperemia in both kidney cortex and medulla, as well as degeneration and necrosis in the tubulus epithelium, was observed. In the LTB + Cd group, mild interstitial hyperemia and mononuclear cell infiltration was detected. Resultantly, it can be said that LTB at this dose has non-toxic effects and some beneficial effects for liver and kidney damage caused by acute Cd toxicity.

Explosive welding is a solid state welding process, which uses a controlled explosive detonation to force two metals together at high pressure. The process has been fully developed with large-scale applications in the manufacturing industry. The explosive bonding technique has an ability to bond a variety of similar and dissimilar materials, and has been applied to fabricate the clad materials and some composites such as multilayered and wire-reinforced materials. In this study, aluminum plates were explosively welded by placing a steel wire mesh between them in order to produce wire mesh reinforced composite materials. The steel wire meshes were placed at two different orientations (45 degrees and 90 degrees). The wire mesh was used to improve the mechanical properties of the explosively welded aluminum plates. Hardness, tensile strength, toughness, bending and microstructure of the explosively welded composite materials were evaluated. The tensile and toughness tests results showed that the 45 wire mesh reinforced composites exhibited higher strength than unreinforced explosively bonded Al plates. No separation was observed in the interface of the welded composite materials after three-point bending. The highest hardness value was measured for the area near the joining interface. (C) 2015 Politechnika Wroclawska. Published by Elsevier Sp. z o.o. All rights reserved.

Congenital cranial teratomas are usually characterized by complete loss of the normal intracranial architecture. In the majority of reports, the tumors are associated with stillbirth, perinatal death, or significant morbidity after surgical resection. The few reported attempts at total or subtotal tumor resection have had poor outcomes, although there are rare reports of prolonged survival up to 3.5 years following resection of smaller tumors. Neonatal teratomas are rarely located in the scalp. In the literature, there were only a few patients who underwent surgery during the neonatal period with a good outcome; however, all such patients survived. In this paper, we present a neonatal case of huge congenital extracranial immature teratoma on the scalp extending to the orbita, ears, and brain. Examination of the patient revealed a large craniofacial mass and head circumference that was bigger than normal; there were no other neurological deficits. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a multiloculated, heterogeneous cystic mass that was larger than the patient's head, displacing and distorting anatomical structures. MRI showed mass with calcifications, soft tissue, fat, and fluid components. There was deformity and remodeling of the adjacent calvaria. A total surgical excision was performed and histopathological examination showed immature teratoma. The patient's early postoperative course was uneventful. Postoperative CT and MRI were normal. To date, the patient has survived for 6 months without neurological deficit. We conclude that acceptable functional outcomes in the context of massive congenital craniofacial teratomas can be achieved by early radical resection.

The management of mammary hypertrophy is a developing process. The common surgical options for reduction mammaplasty include amputation with free nipple graft as well as the bipedicled, inferior pedicle and vertical pedicle techniques. All techniques are used widely. Disadvantages of these procedures include nipple areola necrosis, insensitivity, hypopigmentation, and poor breast projection. Even with the standard modifications of the original techniques, the resultant breast and nipple may be wide and flat. The purpose of this study was to assess whether combined inferior pyramidal pedicle and superior glandular pedicle reduction mammaplasty can optimize nipple and breast projection. Attention will focus on the viability and sensation of the nipple areola complex. Nine patients with mammary hypertrophy were studied. The change in nipple position ranged from 7 to 13 cm. The amount of tissue removed from each breast ranged from 500 to 1150 g. Nipple/ areola sensation was retained in all cases with the exception of one breast. Nipple/areola necrosis or hypopigmentation were not observed. Optimal central breast projection was maintained in all patients, and postoperative evaluation was carried out at 12 and 22 months. The patient satisfaction was very high.

Smoking causes various aero-digestive neoplasms, some cardiovascular diseases, respiratory pathologies, and cardiovascular disorders. Surgeons have observed an association between impaired wound healing and smoking. In plastic surgery, cigarette smoking should be forbidden before and after surgery to prevent poor surgical results. In this retrospective study, we presented four major complications related with continuous smoking immediately after surgery. Although we have strongly forbidden smoking for every patient, 4 patients did not follow our advice and continued to smoke. One of them had a breast reconstruction with a pedicled transverse rectus abdominis musculocutaneous flap. Another patient had an abdominoplasty. The third and fourth patients had digital replantation and they were chronic smokers. After their poor surgical outcomes, these heavy smokers received close supervision, but managed to smoke, anyway. Education, psychologic consultation, and sometimes refusing to perform aesthetic or reconstructive surgery are required to minimize postoperative complications.