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We aimed to evaluate the impact of hormone replacement, melatonin, or exercise alone or their combination on oxidative damage and functional status of heart, brain, and aorta of ovariectomized (OVX) rats and to determine whether the signaling pathway is dependent on sirtuin-1 (SIRT1). Ovariectomized Sprague Dawley rats were orally given either a hormone replacement therapy (1 mg/kg/day,17β estradiol; HRT) or melatonin (4 mg/kg/day) or HRT + melatonin treatments or tap water, while each group was further divided into sedentary and exercise (30 min/5 days/week) groups. After the heart rate measurements and memory tests were performed, trunk blood was collected at the end of the 10th week to determine metabolic parameters in serum samples. Tissue samples of abdominal aorta, heart, and brain were taken for biochemical measurements and histopathological evaluation. Heart rates and memory performances of the OVX rats were not changed significantly by none of the applications. Melatonin treatment or its co-administration with HRT upregulated the expressions of IL-10 and SIRT1, reduced the expressions of IL-6 and TNF-α, and reduced DNA damage in the hearts and thoracic aortae of non-exercised rats. Co-administration of melatonin and HRT to exercised OVX rats reduced inflammatory response and upregulated SIRT1 expression in the aortic and cardiac tissues. The present study suggests that melatonin treatment, either alone or in combination with exercise and/or HRT, upregulates SIRT1 expression and alleviates oxidative injury and inflammation in the hearts and aortas of OVX rats. Melatonin should be considered in alleviating cardiovascular disease risk in postmenopausal women., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A new series of 2-pyrazoline derivatives starting from substituted benzodioxole chalcones were designed and synthesized. IR and 1H NMR spectral data and elemental analysis were used to characterize the structures of the synthesized compounds. The cytotoxic activities on HeLa, MCF-7 cancer cell lines and NIH-3T3 for these compounds were tested by using MTT assay. Among the synthesized compounds 2d, 2j, 3j and 3n against MCF-7 cells, and 3c against HeLa exhibited significant cytotoxic activity with IC50 between 10.08 and 27.63 μM. Compound 3f showed the most potent anticancer activity against both cancer cells with good selectivity (IC50 = 11.53 μM on HeLa with SI = 81.75 and IC50 = 11.37 μM on MCF-7 with SI = 82.90). Furthermore, in silico ADMET analyses were performed and the drug-likeness properties of the compounds were investigated.

Objective: To investigate the levels of C-reactive protein, procalcitonin, calprotectin, interleukin 1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) in both saliva and serum in children with community-acquired pneumonia and to compare the saliva response with the systemic response., Methods: Forty hospitalized children with community-acquired pneumonia aged between 1 mo and 15 y; and 40 healthy controls were included. Both serum and saliva samples were collected on admission and at the time of discharge., Results: Calculated differences between values for each serum and salivary parameter on admission and before discharge named delta (Δ) values were used for correlation analysis. Salivary Δ values of each parameter were moderately/strongly correlated with their corresponding serum Δ levels [IL-1β ÷ (r = 0.554, p < 0.001); IL-6 ÷ (r = 0.484, p = 0.002); PCT ÷ (r = 0.737, p < 0.001); TNF-α ÷ (r = 0.587, p < 0.001); CRP ÷ (r = 0.703, p < 0.001); and calprotectin ÷ (r = 0.774, p < 0.001)]., Conclusions: This study will evaluate the reflection of systemic changes in saliva and the efficacy of saliva in pediatric patients with pneumonia. Results will highlight saliva potential use as a biofluid for systemic monitoring in this patient group., (© 2021. Dr. K C Chaudhuri Foundation.)

The green method of nanoparticle synthesis, which is an environment and living-friendly method, is an updated subject that has appeared as an alternative to conventional methods such as physical and chemical synthesis. In this presented study, the green synthesis of magnetic iron oxide nanoparticles (IONPs) from iron (III) chloride by using Brassica oleracea var. capitata sub.var. rubra aqueous peel extract has been reported. The prepared IONPs were characterized with fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-VIS), zeta potential, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The cytotoxic effects of IONPs on MCF-7 breast cancer cell line were studied by MTT assay, and migrative effect of its were carried out by the wound healing assay. It was found that the mean particle size of IONPs was 675 ± 25 nm, and the polydispersity index was 0.265 PDI. It was also determined that these nanoparticles had an anti-proliferative impact on the MCF-7 breast cancer cell line depending on the dosage. Characterization results support the successful synthesis of nanoparticles, and the dose-dependent cytotoxic effects of nanoparticles on MCF-7 cells also make it a potential chemotherapeutic agent for breast cancer treatment., Competing Interests: CONFLICT OF INTEREST: none declared, (Copyright © 2021 The Author(s).)

The aim of this study is to examine the possible benefits of exercise and caloric restriction (CR) on cardiovascular hemodynamics, erectile function, and antioxidant system in metabolic syndrome (MS). Sixty male Spraque-Dawley rats were divided into five groups; control, MS, MS + CR, MS + exercise (EXC), and MS + CR + EXC. To induce MS, 10% fructose solution was applied for 3 months. Thereafter, in CR groups calorie was restricted 40% and in EXC groups swimming was performed for 6 weeks. Body weight, blood glucose, and blood pressure (BP) levels were measured before and after MS induction and at the end of the experiment. After decapitation, tumor necrosis factor (TNF)-α, adiponectin (ADP), and plasminogen activator inhibitor (PAI)-1 levels were investigated in blood, oxidative stress parameters were examined in heart, aorta, and corpus cavernosum (CC) tissues. Isometric contraction in isolated tissue bath was studied in aorta and CC tissues. Animals subjected to exercise and CR had decreased BP and blood glucose levels. Impaired contraction-relaxation responses in MS group were improved with exercise and CR. MS-induced increase in TNF-α, PAI-1, malondialdehyde (MDA), and decrease in ADP, glutathione (GSH), and superoxide dismutase (SOD) were normalized with exercise and CR. Exercise and CR may be beneficial against changes in cardiovascular hemodynamics caused by MS., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

A new series of N-(4-(1-Phenyl-5-aryl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-4-substitutedbenzamide derivatives were designed and synthesized from new chalcone derivatives. All newly synthesized compounds were determined by using IR, 1 H-NMR, 13 C-NMR spectroscopic methods, elemental analysis and evaluated for their in vitro antiproliferative activities on HeLa, MCF-7, MKN-45 cancer cell lines and NIH-3T3 cell line using MTT assay. Expression of Bax and Bcl-2 proteins was detected by Western-blot analysis and caspase-3 enzyme activity was measured. Notably, compounds 1f and 2f showed a significant cytotoxic effect in all three cancer cells and did not display cytotoxicity on NIH-3T3 normal cells. (IC 50  = 26.66 ± 2.73 μM on HeLa, IC 50  = 9.41 ± 2.19 μM on MCF-7, IC 50  = 5.17 ± 3.54 μM on MKN-45 for 1f. IC 50  = 17.96 ± 3.34 μM on HeLa, IC 50  = 0.69 ± 0.13 μM on MCF-7, IC 50  = 0.88 ± 0.16 μM on MKN-45 for 2f.) Moreover, 1f and 2f upregulated protein expression level of Bax and downregulated protein expression level of Bcl-2 in cells. Similarly, caspase-3 activity was increased in cells via 1f and 2f. It can be concluded that 1f and 2f activated apoptosis by inducing mitochondrial apoptotic proteins in HeLa, MCF-7, MKN-45. This could be potentially new anti-cancer derivatives and used to contribute to new therapeutic development., Competing Interests: Declaration of Competing Interest The authors 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 © 2020 Elsevier Inc. All rights reserved.)

In trying to develop new anticancer agents, a series of sulfonylhydrazones were synthesized. All synthesized compounds were checked for identity and purity using elemental analysis, TLC and HPLC and were characterized by their melting points, FT-IR and NMR spectral data. All synthesized compounds were evaluated for their cytotoxic activity against prostate cancer (PC3), breast cancer (MCF-7) and L929 mouse fibroblast cell lines. Among them, N'-[(2-chloro-3-methoxyphenyl)methylidene]-4-methylbenzenesulfonohydrazide (3k) showed the most potent anticancer activity against both cancer cells with good selectivity (IC 50  = 1.38 μM on PC3 with SI = 432.30 and IC 50  = 46.09 μM on MCF-7 with SI = 12.94). Further investigation confirmed that 3k displayed morphological alterations in PC3 and MCF-7 cells and promoted apoptosis through down-regulation of the Bcl-2 and upregulation of Bax expression. Additionally, compound 3k was identified as the most potent COX-2 inhibitor (91% inhibition) beside lower COX-1 inhibition. Molecular docking of the tested compounds represented important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme. Overall, the lead compound 3k deserves further development as a potential anticancer agent. Sulfonylhydrazones was synthesized and N'-[(2-chloro-3-methoxyphenyl)methylidene]-4- methylbenzenesulfonohydrazide (3k) was identified as the most potent anticancer agent and COX-2 inhibitor. In addition, this compound docked inside the active site of COX-2 succesfully.

The aim of this study is to investigate the therapeutic potential of adipose-derived mesenchymal stem cell (AD-MSC) from brown adipose tissue on erectile dysfunction (ED) in experimentally induced spinal cord injury in rats. 24 male Wistar rats were divided into 3 groups; control, spinal cord injury (SCI) + vehicle, and SCI + AD-MSC. To induce SCI, a standard weight-drop method that induced a moderate to severe injury (100 g/cm force) at T7-T10, was used. AD-MSC (3 × 105 cells /5 μL) was applied by local transplantation into the region of injury. At the end of four-weeks, rats underwent neurological examinations and then intracavernosal and mean arterial pressures (ICP and MAP) measurements. After decapitation, spinal cord and cavernosal tissue samples were taken to analyze neuronal nitric oxide synthase (n-NOS), proto-oncogene protein c-FOS and nerve growth factor (NGF). Tissues were also examined histologically. Spinal cord injury caused decrease on NGF and n-NOS levels while c-FOS was increased. The ICP/MAP value in vehicle-treated SCI rats was found to be significantly higher than the control group. On the other hand, in SCI + AD-MSC group, all these parameters were reversed back to control levels. AD-MSC therapy may be beneficial against erectile dysfunction in experimentally induced SCI by ameliorating neuronal damage.

Aims: The purpose of the present study was to investigate the potential antioxidant, anti-apoptotic and sperm function-preserving effects of estrogen, estrogen receptor (ER)α and ERβ agonists in a rat model of testis torsion-detorsion (T/D)., Main Methods: Under anesthesia, 6-8-week-old male Sprague-Dawley rats underwent sham-operation or testicular torsion by fixing left testis rotated at 720° for 2 h. After detorsion, rats were treated with ERα agonist (1 mg/kg/day, subcutaneously, sc) or ERβ agonist (1 mg/kg/day, sc) or estradiol (E 2 , 1 mg/kg/day, in drinking water) or vehicle on the following two days. On the third day, testicular blood-flow was recorded and then left testes were extracted for molecular and histochemical analysis., Key Findings: The findings showed that reduced testicular blood-flow following torsion was partially restored on the 3rd day of detorsion, while treatments with either of the ER agonists or E 2 returned blood flow fully back to the control levels. When the testis-torsioned rats were given ERβ agonist during the detorsion period, tubular injury was lessened, sperm count and motility were increased, while the production of reactive oxygen metabolites and apoptosis in the testis tissues were totally suppressed. Although a down-regulated expression of androgen receptor (AR) along with a reduction in serum testosterone level was observed in the vehicle-treated T/D group, all three treatments up-regulated the expressions of AR and its mRNA, while ERα agonist and E 2 suppressed the testosterone level., Significance: ERβ receptor activation during the post-ischemic period may be beneficial in protection against torsion-related oxidant testicular injury and infertility., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Testicular torsion causes ischemia-reperfusion injury and an increased risk of infertility. Nesfatin-1 is a novel peptide with antioxidant, anti-inflammatory and anti-apoptotic properties. In the present study, we aimed to investigate the putative beneficial effects of nesfatin-1 on oxidative injury and impaired testicular function induced by testis torsion. Under anesthesia, male Sprague-Dawley rats (180-230 g; n = 24) had sham-operation or they underwent testicular torsion by rotating the left testis 720° and fixing it for 2 h, followed by a 2-h detorsion. Rats in each group were treated intraperitoneally with either nesfatin-1 (0.3 μg/kg) or saline prior to the torsion or sham-torsion. At the end of the 4-h experimental period, tissue samples were removed for evaluation of spermatozoa, molecular and histochemical analyses. In saline-treated torsion/detorsion group, a high percentage of abnormal spermatozoa with head defects was observed, which was abolished in nesfatin-1-treated torsion/detorsion group. The levels of 8-OHdG, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, caspase-3 were increased in the saline-treated torsion/detorsion group as compared to sham-operated group, while nesfatin-1 pre-treatment significantly decreased the expressions of the pro-inflammatory cytokines, depressed apoptosis, and also reduced the tubular degeneration. In addition, nesfatin-1 in torsion/detorsion group elevated expressions of transforming growth factor (TGF)-beta and reduced expressions of protein kinase B (AKT) and cAMP response element binding protein (CREB) in the testis tissue. The present findings show that nesfatin-1, by regulating AKT and CREB signaling pathways and pro-inflammatory/anti-inflammatory cytokine balance, preserves the spermatogenic cells and ameliorates torsion-detorsion-induced tubular degeneration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The present study aimed to investigate the effects of Roux-en-Y gastric bypass (RYGB) and prosthesis placement on gastric emptying rate in conjunction with serum ghrelin-obestatin-leptin responses in non-obese rats with intact or denervated afferent innervation., Methods: Under anesthesia, male Sprague-Dawley rats underwent either sham operation, RYGB, prosthesis, and/or Gregory cannula placement. Three weeks later, liquid or solid gastric emptying tests were performed and serum ghrelin, leptin and obestatin levels were measured., Results: Both prosthesis placement and RYGB surgery delayed non-nutrient liquid emptying; while solid nutrient emptying was delayed only by RYGB. Nutrient-dependent (acid, hyperosmolal and peptone) delay in liquid emptying was abolished in rats with prosthesis. By vagal afferent denervation, delayed liquid emptying was abolished, while solid emptying was further delayed in rats with prosthesis. Ghrelin and obestatin levels were depressed in prosthesis-placed rats, but RYGB surgery had no impact on both levels. Leptin level was elevated in solid-food-given rats with prosthesis, but not changed in RYGB group, while it was reduced following liquid meal. All the changes observed in ghrelin, obestatin, or leptin levels in response to meal ingestion were reversed with vagal afferent denervation., Conclusions: Both RYGB and prosthesis placement had delaying effects on gastric emptying rate of non-obese rats. Our results indicate that the short-term changes in gastric motility and hormone responses induced by volume reduction are reversed by afferent denervation, suggesting that sparing the vagal innervation could be essential for reaching optimum motility and hormone changes expected after bariatric surgery.

A series of diflunisal 4-thiazolidinones were synthesized. Some selected compounds were determined at one dose towards the full panel of 60 human cancer cell lines by National Cancer Institute. 2',4'-Difluoro-4-hydroxy-N-[4-oxo-2-(thiophen-2-yl)-1,3-thiazolidin-3-yl]biphenyl- 3-carboxamide (4a) demonstrated the most marked effect on K-562 cancer cell line with 58.59 % growth inhibition at 10 μM. Compound 4a was evaluated in vitro using the MTT colorimetric method against human leukemia cell line K-562 and mouse embryonic fibroblasts cell line NIH- 3T3 at different doses for cell viability and growth inhibition. Compound 4a exhibited anticancer activity with IC50 value of 5.2 μM against K-562 cells and did not display cytotoxicity towards NIH-3T3 cells compared with diflunisal. In addition, this compound could be an interesting prototype as an antiproliferative agent.

It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 µg/kg) or atropine (50 μg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1β and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1β and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1β and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Spinal cord injury (SCI) leads to an inflammatory response that generates substantial secondary damage within the tissue besides the primary damage. Leukotrienes are biologically active 5-lipoxygenase products of arachidonic acid metabolism that are involved in the mediation of various inflammatory disorders including SCI. In this study, we investigated the possible protective effects of montelukast, a leukotriene receptor blocker, on SCI-induced oxidative damage. Wistar albino rats (n=24) were divided randomly as control, vehicle- or montelukast (10mg/kg, ip)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury at T10 was used. Vehicle or montelukast were administered to the injured animals 15 min after injury. At seven days post-injury, neurological examination was performed and rats were decapitated. Blood samples were taken to evaluate leukotriene B4 levels, and pro-inflmamatory cytokines (TNF-α, IL-1β) while in spinal cord and urinary bladder samples malondialdehyde (MDA), glutathione (GSH), luminol chemiluminescence (CL) levels and myeloperoxidase (MPO) and caspase-3 activities were determined. Tissues were also evaluated histologically. SCI caused significant decreases in tissue GSH, which were accompanied with significant increases in luminol CL and MDA levels and MPO and caspase-3 activities, while pro-inflammatory cytokines in the plasma were elevated. On the other hand, montelukast treatment reversed these parameters and improved histological findings. In conclusion, SCI caused oxidative tissue injury through the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues, and the neuroprotective and antiapoptotic effects of montelukast are mediated by the inhibition of lipid peroxidation, neutrophil accumulation and pro-inflammatory cytokine release. Moreover, montelukast does not only exert antioxidant and antiapoptotic effects on the spinal cord, but it has a significant impact on the bladder tissue damage secondary to SCI., (Copyright © 2012 Elsevier Inc. All rights reserved.)