The role of gender differences in the outcome of juvenile social isolation: Emphasis on changes in behavioral, biochemical and expression of nitric oxide synthase genes alteration.

Social isolation can cause serious problem in performance of individuals in community. As gender differences may cause variation results in the severity of depressive behavior and response of patients to therapy, the impact of gender and the interaction of the level of endocrine secretion in depression were investigated in this study. Wistar rats of both sexes were subjected to post-weaning social isolation (PWSI) conditions and, together with the control group, experienced several behavioral tests including open-field Test (OFT), elevated plus maze (EPM), force swimming test (FST), splash test and novel object recognition test (NOR). Hippocampal tissue was isolated to measure biochemical factors such as nitric oxide level, FRAP amount, MDA level. In addition, real-time-PCR test was used to quantify the genes expression level of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). On the other hand, sexual hormone levels in blood were measured. Both cognitive and behavioral f unctions were declined as the result of PWSI induction in male and diestrus female rats. The consequent surge of estradiol during estrous phase seems to suppress the accumulation of reactive oxygen species (ROS), and modulate iNOS and nNOS expression. In conclusion, while the pattern of PWSI in surge cellular antioxidants, raising cellular ROS level is gender-specific, this alleviation was in relation with the drop of estradiol and unrelated with testosterone level.

Injectable, antibacterial, and oxygen-releasing chitosan-based hydrogel for multimodal healing of bacteria-infected wounds.

Bacterial infection is one of the main challenges of wound healing. It imposes financial and healthcare costs. The emergence of antibiotic-resistant bacteria has increased concerns about this challenge, and made finding alternative solutions a crucial aim. We created a new, antibacterial, multifunctional hydrogel with synergistic chemodynamic and photothermal features for wound-healing applications. We fabricated a chitosan (CT)-based hydrogel containing tannic acid (TA), Fe, and MnO2 nanosheets (CT-TA-Fe-MnO2) via a simple method and characterized it. The antibacterial features (resulting from the production of reactive oxygen species within bacterial cells) and healing ability (via anti-inflammatory and hemostatic features) of the hydrogel were confirmed in vitro. In vivo results revealed the effectiveness of the CT-TA-Fe-MnO2 hydrogel in decreasing the hemostatic time, improving anti-inflammatory effects, and promoting wound healing during 14 days by enhancing the deposition and maturation of collagen fibers without affecting the vital organs. The fabricated CT-TA-Fe-MnO2 hydrogel could be a promising candidate with antibacterial and anti-inflammatory activities suitable for wound-healing applications.

Engineering a platelet-rich plasma-based multifunctional injectable hydrogel with photothermal, antibacterial, and antioxidant properties for skin regeneration.

Wound healing remains a significant challenge worldwide, necessitating the development of new wound dressings to aid in the healing process. This study presents a novel photothermally active hydrogel that contains platelet-rich plasma (PRP) for infected wound healing. The hydrogel was formed in a one pot synthesis approach by mixing alginate (Alg), gelatin (GT), polydopamine (PDA), and PRP, followed by the addition of CaCl2 as a cross-linker to prepare a multifunctional hydrogel (AGC-PRP-PDA). The hydrogel exhibited improved strength and good swelling properties. PDA nanoparticles (NPs) within the hydrogel endowed them with high photothermal properties and excellent antibacterial and antioxidant activities. Moreover, the hydrogels sustained the release of growth factors due to their ability to protect PRP. The hydrogels also exhibited good hemocompatibility and cytocompatibility, as well as high hemostatic properties. In animal experiments, the injectable hydrogels effectively filled irregular wounds and promoted infected wound healing by accelerating re-epithelialization, facilitating collagen deposition, and enhancing angiogenesis. The study also indicated that near-infrared light improved the healing process. Overall, these hydrogels with antibacterial, antioxidant, and hemostatic properties, as well as sustained growth factor release, show significant potential for skin regeneration in full-thickness, bacteria-infected wounds.

Edaravone Improves Streptozotocin-Induced Memory Impairment via Alleviation of Behavioral Dysfunction, Oxidative Stress, Inflammation, and Histopathological Parameters.

Alzheimer's disease (AD), as the main cause of dementia, has a progressive and neurodegenerative pattern with number of cases increasing over the next decades. Therefore, discovering an effective treatment with the ability to invert memory impairment and pathophysiological events of AD seems to be required. The present study performed to investigate the probable effects of Edaravone (EDV) in AD-like disorder induced by intracerebroventricular streptozotocin (ICV-STZ) administration in mice. This study also compares the two different methods of ICV-STZ in the memory impairment induction. NMRI male mice were administrated with 3 mg/kg of STZ for two times during 48 hours span, and after 24 hours, animals were treated with EDV (5 and 10 mg/kg), Donepezil, and Memantine for 14 days. After behavioral tests regarding memory and cognitive function, animals were sacrificed, and the hippocampi were utilized for further analyses. Our results demonstrated that administration of STZ induced memory impairment in the Morris water maze (MWM) test and decreased the discriminative factor in novel object recognition (NOR). The biochemical output shows a significant decrease in ferric reducing antioxidant power (FRAP) and glutathione (GSH) levels followed by increase in malondialdehyde (MDA) and protein carbonylation (PCO) levels. The output showed no difference between the patterns of AD-like disorder induction. Following our treatment groups, administration of EDV (5 and 10 mg/kg), Donepezil, and Memantine significantly improved memory performance and discriminatory behavior. Aforementioned treatments managed to improve FRAP and GSH content of hippocampus, while significantly attenuating MDA, PCO, and nitric oxide overproduction. In addition, no significant difference has been observed between the effect of 5 and 10 mg/kg EDV application. It was supposed that EDV managed to ameliorate memory dysfunction, discriminatory behavior, oxidative stress, and cellular antioxidant power in a dose-independent pattern in mice.

Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery.

Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. In vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage.

Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model.

Background: Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Methods: Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. Results: HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Conclusions: Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.

Injectable Antibacterial Gelatin-Based Hydrogel Incorporated with Two-Dimensional Nanosheets for Multimodal Healing of Bacteria-Infected Wounds.

The design and development of multifunctional injectable hydrogels with high photothermal antibacterial activity and shape adaptability to accelerate bacteria-infected wound healing is of critical importance in clinical applications. In this study, a hybrid hydrogel composed of gelatin, iron, and MnO2 nanosheets was prepared by multiple interactions, including coordinative and hydrogen bonding as well as electrostatic attraction. The introduced MnO2 and Fe components made the hydrogels photothermally and chemodynamically active, thereby endowing them with potent antibacterial capabilities against both Gram-negative and Gram-positive bacteria. Because of the Fenton activity of the hydrogels, they could produce abandoned oxygen, which is highly crucial in the healing process of wounds. They also showed good cytocompatibility and hemocompatibility as well as high hemostatic properties. Moreover, the injectable hydrogels could fill irregular wounds and significantly accelerate bacteria-infected wound healing through decreasing the inflammatory response and increasing blood vessels. These features indicated the promising potential of the multifunctional hydrogel for healing infected full-thickness wounds.

Protective role of ellagic acid and taurine against fluoxetine induced hepatotoxic effects on biochemical and oxidative stress parameters, histopathological changes, and gene expressions of IL-1ß, NF-κB, and TNF-α in male Wistar rats.

PURPOSES: Hepatic bioactivation of fluoxetine (FXN) could increase free radicals' generation provoking hepatotoxicity. Therefore, the protective effects of ellagic acid (EA) and taurine (TAU) treatments against fluoxetine-induced liver damage in rats were examined. MATERIALS AND METHODS: Sixty four male Wistar rats were randomly assigned to 8 groups (n = 8). Group (1) Control, group (2) FXN, group (3) FXN + EA, group (4) FXN + TAU, group (5) FXN + EA + TAU, group (6) EA, group (7) TAU, and group (8) EA + TAU. Then, the serum and tissue parameters of the oxidative stress were examined. KEY FINDINGS: FXN significantly raised serum MDA, protein carbonyl, lipid profile, ALT, AST, ALP, total bilirubin, serum IL-1ß; and gene expressions of IL-1ß, NF-κB, and TNF-α. Moreover, it significantly decreased HDL-C, ferric reducing antioxidant power (FRAP), catalase activity, vitamin C, and SOD activity in the liver compared to group 1. When compared to group 2, EA and TAU treatment dramatically increased antioxidant capacity and lowered hepatotoxic biochemical markers and cellular inflammation. Results also showed a protective effect of treatment against oxidative damage caused by hepatocytes' cytoarchitecture. SIGNIFICANCE: Our study concluded the beneficial effects of EA and TAU on FXN-induced hepatotoxicity. These effects were derived from free radical scavenging properties and the anti-inflammatory effects related to IL-1ß, NF-κB, and TNF-α gene expression inhibition.

The effects of P. atlantica as a libido booster and sexual enhancer on the reproductive system of male rats.

Background and aim: Alongside the advancement of various modern treatments, attention has recently been focused on finding alternative infertility treatments based on diet and herbal medicine. Pistacia atlantica (wild pistachio; Baneh) is a plant species traditionally known as a libido booster and sexual enhancer. Experimental procedure: The study aim was to evaluate the effects of a P. atlantica-enriched diet on the functions of the reproductive system of male rats. Results and conclusion: Results revealed that the diet containing 20% P. atlantica doubled testosterone levels in the treatment group compared to the control. It decreased the total bodyweight, while significantly increased the ratios of the seminal vesicles, testis, and epididymis to the bodyweight of rats. The sperm count in the treatment group was 4.8 × 106/mL, which was significantly more than the control group (4.2 × 106/mL). Furthermore, the utilization of P. atlantica significantly raised HDL levels, though it reduced the LDL and TG levels and the concentration of testis MDA. Concerning other factors, the 20% of P. atlantica considerably increased the serum level of Zinc and vitamin D. Histomorphometric analysis revealed that the diet increased the testicular capsule thickness, whereas it did not cause any significant change in the diameter of the seminiferous tubule, the number of Leydig cells, and Sertoli cells. Additionally, the repopulation index, tubular differentiation index, and spermiogenesis index increased in the treatment group. Molecular analysis showed that the prescribed diet increased the expression of both oxytocin (OXT) and its receptor (OXTR) genes, improving the reproductive system function.

Acetylsalicylic acid-induced alterations in male reproductive parameters in Wistar rats and the effect of sprint interval training.

The present study investigated the effect of a 5-week ASA treatment on male reproductive parameters in Wistar rats; moreover, the potential benefits of a 4-week sprint interval training (SIT) on these measures following ASA treatment were investigated. A total of 25 male rats were obtained and randomly assigned to the control group (C, n = 10) and the ASA treatment group (EP, n = 15). After 5 weeks, five rats from each group were killed and the effect of ASA treatment on the reproductive parameters was assessed. Then, the ASA treatment terminated and the remaining 10 ASA-treated rats were divided into the non-treatment group (NT, n = 5) and the exercise training group (ET, n = 5), which performed SIT 3 sessions/week for 4 weeks. Five weeks of ASA treatment resulted in a statistically significant decrease in serum testosterone level, Leydig cell number, sperm count, sperm motility, sperm viability, TDI, SI and RI, and it resulted in a significant increase in sperm nucleus maturity and sperm DNA fragmentation (p Ë‚ 0.05). Furthermore, 4 weeks of SIT reversed all the ASA-induced changes in male reproductive parameters (p < 0.05), but not the number of seminiferous tubules and the sperm motility (p > 0.05). A subchronic dose of ASA could lead to adverse alterations in male reproductive parameters and SIT is beneficial in reversing those alterations.

Hepatoprotective effects of Lactobacillus plantarum 299v supplemented via drinking water against aflatoxin-induced liver damage.

The aim of this study was to examine the impact of intake of a lactic acid bacterium, Lactobacillus plantarum 299v (Lp299v) on aflatoxin-induced hepatotoxicity in broilers. For this, broilers were intoxicated with dietary aflatoxins and simultaneously treated with live Lp299v in drinking water. One-day-old male broilers were divided into eight groups (n = 10/group) as follows. Aflatoxin groups fed basal diet contaminated with aflatoxins (200 or 2000 ppb). The probiotic groups received drinking water enriched with live (Lp299v) (108 CFU/ml). A group of birds was given a commercial mycotoxin binder (2.5 g/kg feed). Control groups received basal diet without probiotic or aflatoxin binder. The growth performance was calculated for the entire period (0-42 days), and blood and liver specimens were processed for histology and determination of liver damage markers. Results showed extensive damage including bile duct hyperplasia, hepatocellular ballooning, and necrosis in chickens fed aflatoxin alone. However, liver lesions were limited to lobular inflammation and pyknosis in broilers treated with aflatoxins along with Lp299v. The histology of the liver tissues from the birds on aflatoxin-free diet + probiotic appeared to be normal when compared to the respective controls. Histopathological indices in different experimental groups were corroborated with the liver damage markers namely, serum ALT, AST, LD, and γ-GT. It is concluded that the improvement in the growth performance and prevention of aflatoxin-related liver lesions could be mainly assigned to the probiotic therapy for the entire period of breeding, although the aflatoxin-binding ability of the Lp299v in inactivation of aflatoxins cannot be ruled out.RESEARCH HIGHLIGHTS Aflatoxin-related liver damage progression was inhibited by probiotics in broilers.Aflatoxin inactivation by probiotics can be assessed by liver histopathology.Growth performance in broilers was improved following the intake of probiotics.