Interaction of estradiol and renin-angiotensin system with microRNAs-21 and -29 in renal fibrosis: focus on TGF-ß/smad signaling pathway.

Kidney fibrosis is one of the complications of chronic kidney disease (CKD (and contributes to end-stage renal disease which requires dialysis and kidney transplantation. Several signaling pathways such as renin-angiotensin system (RAS), microRNAs (miRNAs) and transforming growth factor-ß1 (TGF-ß1)/Smad have a prominent role in pathophysiology and progression of renal fibrosis. Activation of classical RAS, the elevation of angiotensin II (Ang II) production and overexpression of AT1R, develop renal fibrosis via TGF-ß/Smad pathway. While the non-classical RAS arm, Ang 1-7/AT2R, MasR reveals an anti-fibrotic effect via antagonizing Ang II. This review focused on studies illustrating the interaction of RAS with sexual female hormone estradiol and miRNAs in the progression of renal fibrosis with more emphasis on the TGF-ß signaling pathway. MiRNAs, especially miRNA-21 and miRNA-29 showed regulatory effects in renal fibrosis. Also, 17ß-estradiol (E2) is a renoprotective hormone that improved renal fibrosis. Beneficial effects of ACE inhibitors and ARBs are reported in the prevention of renal fibrosis in patients. Future studies are also merited to delineate the new therapy strategies such as miRNAs targeting, combination therapy of E2 or HRT, ACEis, and ARBs with miRNAs mimics and antagomirs in CKD to provide a new therapeutic approach for kidney patients.

Video game addiction is associated with early stage of inhibitory control problems: An event-related potential study using cued Go/NoGo task.

Video game addiction (VGA) is associated with cognitive problems, particularly deficits in inhibitory control. The present study aimed to investigate behavioural responses and event-related potential associated with specific response inhibition using the cued Go/NoGo task to examine the effects of VGA on brain activity related to response inhibition. Twenty-five individuals addicted to video games (action video games) and 25 matched healthy controls participated in the study. The results showed that the VGA group had significantly more commission error in the NoGo trials and faster reaction time in the Go trials compared with the control group. The event-related potential analyses revealed significant reductions in amplitudes of N2 cue and N2 NoGo in the VGA group. While there was no significant difference between the N2 amplitudes of the Go and NoGo trials in the VGA group, the control group had a larger N2 amplitude in the NoGo trials. These results indicate that VGA subjects have difficulties in the early stages of response inhibition, as well as some level of impairment in proactive cognitive control.

Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training.

BACKGROUND: Type 2 diabetes (T2D) leads to serious respiratory problems. This study investigated the effectiveness of high-intensity interval training (HIIT) on T2D-induced lung injuries at histopathological and molecular levels. METHODS: Forty-eight male Wistar rats were randomly allocated into control (CTL), Diabetes (Db), exercise (Ex), and Diabetes + exercise (Db + Ex) groups. T2D was induced by a high-fat diet plus (35 mg/kg) of streptozotocin (STZ) administration. Rats in Ex and Db + Ex performed HIIT for eight weeks. Tumor necrosis factor-alpha (TNFα), Interleukin 10 (IL-10), BAX, Bcl2, Lecithin, Sphingomyelin (SPM) and Surfactant protein D (SPD) levels were measured in the bronchoalveolar lavage fluid (BALF) and malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured in lung tissue. Lung histopathological alterations were assessed by using H&E and trichrome mason staining. RESULTS: Diabetes was significantly associated with imbalance in pro/anti-inflammatory, pro/anti-apoptosis and redox systems, and reduced the SPD, lecithin sphingomyelin and alveolar number. Performing HIIT by diabetic animals increased Bcl2 (P < 0.05) and IL10 (P < 0.01) levels as well as surfactants components and TAC (P < 0.05) but decreased fasting blood glucose (P < 0.001), TNFα (P < 0.05), BAX (P < 0.05) and BAX/Bcl2 (P < 0.001) levels as well as MDA (P < 0.01) and MDA/TAC (P < 0.01) compared to the diabetic group. Furthermore, lung injury and fibrosis scores were increased by T2D and recovered in presence of HIIT. CONCLUSION: These findings suggested that the attenuating effect of HIIT on diabetic lung injury mediated by reducing blood sugar, inflammation, oxidative stress, and apoptosis as well as improving pulmonary surfactants components.

High-intensity intermittent training ameliorates methotrexate-induced acute lung injury.

Inflammation and oxidative stress are recognized as two primary causes of lung damage induced by methotrexate, a drug used in the treatment of cancer and immunological diseases. This drug triggers the generation of oxidants, leading to lung injury. Given the antioxidant and anti-inflammatory effects of high-intensity intermittent training (HIIT), our aim was to evaluate the therapeutic potential of HIIT in mitigating methotrexate-induced lung damage in rats. Seventy male Wistar rats were randomly divided into five groups: CTL (Control), HIIT (High-intensity intermittent training), ALI (Acute Lung Injury), HIIT+ALI (pretreated with HIIT), and ALI + HIIT (treated with HIIT).HIIT sessions were conducted for 8 weeks. At the end of the study, assessments were made on malondialdehyde, total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (Gpx), myeloperoxidase (MPO), interleukin 10 (IL-10), tumor necrosis factor-alpha (TNF-α), gene expression of T-bet, GATA3, FOXP3, lung wet/dry weight ratio, pulmonary capillary permeability, apoptosis (Caspase-3), and histopathological indices.Methotrexate administration resulted in increased levels of TNF-α, MPO, GATA3, caspase-3, and pulmonary edema indices, while reducing the levels of TAC, SOD, Gpx, IL-10, T-bet, and FOXP3. Pretreatment and treatment with HIIT reduced the levels of oxidant and inflammatory factors, pulmonary edema, and other histopathological indicators. Concurrently, HIIT increased the levels of antioxidant and anti-inflammatory factors.

Inhalation of Spray-Dried Extract of Salvia rosmarinus Spenn Alleviates Lung Inflammatory, Oxidative, and Remodeling Changes in Asthmatic Rats.

INTRODUCTION: For centuries, Salvia rosmarinus Spenn has been applied as folk medicine to cure different diseases due to its anti-inflammatory, antibacterial, antioxidant, antifungal, and antitumor effects. To find bioactive medicinal herbs exerting a protective effect on airway inflammation and remodeling, we assessed the anti-oxidative and anti-inflammatory effects of an aqueous spray-dried extract of Salvia rosmarinus Spenn. (rosemary) in an ovalbumin-induced asthmatic rat model. METHODS: Rats were randomly divided into normal control (control), asthma, asthma+rosemary extract (RE) (13 mg/kg), asthma+RE (50 mg/kg), and asthma+budesonide groups. After 50 days, animals were anesthetized, and then blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for subsequent serological and pathological studies. Histopathology of lung tissues was evaluated by H&E staining. The oxidative stress parameters and airway inflammation factors in BALF and lung tissue were explored. RESULTS: Using thin layer chromatography, the presence of rosmarinic acid was confirmed in aqueous extract of rosemary. Furthermore, RE markedly decreased immunoglobulin E levels (50 mg/kg; p < 0.001 vs. asthma group) and inflammatory cytokines (50 mg/kg; p < 0.001 vs. asthma group) and increased antioxidant enzymes (50 mg/kg, p < 0.001 vs. asthma group). Furthermore, RE at a concentration of 50 mg/kg obviously reduced the number of inflammatory cells, goblet cells, and pathological changes compared to the asthma group. CONCLUSION: The results showed that RE administration might prevent or alleviate allergic asthma-related pathological change, probably via antioxidant and anti-inflammatory mechanisms.

Comparison of preventive and therapeutic effects of continuous exercise on acute lung injury induced with methotrexate.

Methotrexate (Mtx) is used to treat various diseases, including cancer, arthritis and other rheumatic diseases. However, it induces oxidative stress and pulmonary inflammation by stimulating production of reactive oxygen species and cytokines. Considering the positive effects of physical activity, our goal was to investigate the preventive and therapeutic role of continuous training (CT) on Mtx-induced lung injury in rats. The rats were divided into five groups of 14 animals: a control group (C); a continuous exercise training group (CT; healthy rats that experienced CT); an acute lung injury with Mtx group (ALI); a pretreatment group with CT (the rats experienced CT before ALI induction), and a post-treatment group with CT (the rats experienced CT after ALI induction). One dose of 20 mg/kg Mtx intraperitoneal was administered in the Mtx and training groups. Forty-eight hours after the last exercise session all rats were sacrificed. According to our results, the levels of tumour necrosis factor-α (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO), GATA binding protein 3 (GATA3) and caspase-3 in the ALI group significantly increased compared to the control group, and the levels of superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), interleukin-10 (IL-10), forkhead box protein 3 (FOXP3), and T-bet decreased. In contrast, compared to the acute lung injury group, pretreatment and treatment with CT reduced TNF-α, MDA, MPO, GATA3 and caspase-3 and increased SOD, GPX, TAC, IL-10, FOXP3 and T-bet levels. The effects of CT pretreatment were more significant than the effects of CT post-treatment. Continuous exercise training effectively reduced oxidative stress and inflammatory cytokines and ameliorated Mtx-induced injury, and the effects of CT pretreatment were more significant than the effects of CT post-treatment. NEW FINDINGS: What is the central question of this study? Considering the high prevalence of lung injury in society, does exercise as a non-pharmacological intervention have ameliorating effects on lung injury? What is the main finding and its importance? Exercise can have healing effects on the lung after pulmonary injury through reducing inflammation, oxidative stress and apoptosis. Considering the lower side effects of exercise compared to drug treatments, the results of this study may be useful in the future.

Myrtenol Ameliorates Recognition Memories' Impairment and Anxiety-Like Behaviors Induced by Asthma by Mitigating Hippocampal Inflammation and Oxidative Stress in Rats.

INTRODUCTION: Asthma is related to neurochemical alterations which affect brain functions and lead to anxiety and cognitive dysfunctions. Myrtenol has sparked considerable interest due to its pharmacological effects, especially for the remediation of chronic disorders. Thus, the present research was designed to evaluate the impacts of myrtenol on anxiety-like behaviors, cognitive declines, inflammation, and oxidative stress in the hippocampus of asthmatic rats. METHODS: Rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Asthma was elicited in the rats by ovalbumin, and the animals were then exposed to myrtenol inhalation. Anxiety-like behavior and memory were assessed by elevated plus maze (EPM) and novel object and location recognition tests. Interleukins (interleukin-6, -17, and -10), tumor necrosis factor α (TNF-α), and oxidative stress biomarkers such as malondialdehyde (MDA), superoxide dismutase (SOD), Glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in the hippocampus were assessed by the ELISA method. RESULTS: The levels of IL-6, IL-17, TNF-α, and MDA decreased, but GPX, SOD, and TAC levels increased in the hippocampus of asthmatic animals due to myrtenol inhalation. CONCLUSION: Myrtenol diminished asthma-induced anxiety-like behaviors and cognitive deficits in asthmatic rats; these effects might have been typically mediated by a reduction in inflammation and oxidative stress.

The Role of Inhaled Estradiol and Myrtenol, Alone and in Combination, in Modulating Behavioral and Functional Outcomes Following Traumatic Experimental Brain Injury: Hemodynamic, Molecular, Histological and Behavioral Study.

BACKGROUND: Traumatic brain injury (TBI) is an important and growing cause of disability worldwide, and its cognitive consequences may be particularly significant. This study assessed the neuroprotective impacts of estradiol (E2), myrtenol (Myr), and the combination of the two on the neurological outcome, hemodynamic parameters, learning and memory, brain-derived neurotrophic factor (BDNF) level, phosphoinositide 3-kinases (PI3K/AKT) signaling, and inflammatory and oxidative factors in the hippocampus after TBI. METHODS: Eighty-four adult male Wistar rats were randomly divided into 12 groups with seven rats in each (six groups to measure intracranial pressure, cerebral perfusion pressure, brain water content, and veterinary coma scale, and six groups for behavioral and molecular studies): sham, TBI, TBI/vehicle, TBI/Myr, TBI/E2, and TBI/Myr + E2 (Myr 50 mg/kg and E2 33.3 µg/kg via inhalation for 30 min after TBI induction). Brain injury was induced by using Marmarou's method. Briefly, a 300-g weight was dropped down from a 2-m height through a free-falling tube onto the head of the anesthetized animals. RESULTS: Veterinary coma scale, learning and memory, brain water content, intracranial pressure, and cerebral perfusion pressure were impaired following TBI, and inflammation and oxidative stress were raised in the hippocampus after TBI. The BDNF level and PI3K/AKT signaling were impaired due to TBI. Inhalation of Myr and E2 had protective effects against all negative consequences of TBI by decreasing brain edema and the hippocampal content of inflammatory and oxidant factors and also by improving BDNF and PI3K/AKT in the hippocampus. Based on these data, there were no differences between alone and combination administrations. CONCLUSIONS: Our results propose that Myr and E2 have neuroprotective effects on cognition impairments due to TBI.

Investigating the effects of Citrullus colocynthis on cognitive performance and anxiety-like behaviors in STZ-induced diabetic rats.

Background: Diabetes can impair cognitive performance and lead to dementia. Patients with type 1 diabetes mellitus (T1DM) are reported with different levels of cognitive dysfunctions in various cognitive domains ranging from general intellectual testing to specific deficits with visuospatial abilities, motor speed, writing, attention, reading, and psychomotor efficiency. The present study aimed to investigate the effect of Citrullus colocynthis on cognitive functions.Methods: A total of 42 male Wistar rats (3-4 months old and weighing 200-250 g) were tested in the current study. Rats were randomly allocated into 3 groups of control, Diabetes, and Diabetes + Drug. The diabetic rats received Citrullus colocynthis extraction orally. The behavioral tests included the open field, elevated plus maze (EPM), novel object recognition (NOR), passive avoidance tests, and Morris Water Maze (MWM) tests. Data were analyzed using student and paired t-tests via SPSS software version 16.Results: Our results showed the protective effects of Citrullus colocynthis administration against cognitive impairments. This is followed by STZ-induced diabetes in the MWM, novel object recognition, and passive avoidance tasks. Also, it was found that Citrullus colocynthis improved anxiety in diabetic rats.Conclusion According to the findings of this study, the administration of 200 mg/kg C. colocynthis once per day for 40 days can lead to ameliorated cognitive impairments and antidiabetic effects such as increasing body weight and decreasing FBS.

Trehalose Attenuates Learning and Memory Impairments in Aged Rats via Overexpression of miR-181c.

MicroRNAs have been recognized as important regulators of the aging process. Trehalose, a natural disaccharide, displays protective effects against neuronal impairment through several mechanisms. However, little is known about the interactive effects of aging and trehalose on behavioral function and underlying miRNA expression patterns in the hippocampus of young and old rats. Male Wistar rats were divided into four groups. Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution for 30 days. Two other groups of aged and young rats received regular tap water. At the end of treatment, rats were assessed for cognitive behavior using the Morris water maze test. The expression level of miR-181c and mir-34c was also measured by qRT-PCR. We found that trehalose treatment reduced learning and memory impairment in old rats compared to control old animals (p < 0.05). In contrast, cognitive performance was not significantly improved in trehalose-treated young rats in comparison with young controls (p > 0.05). We also showed that the expression level of miR-181c was significantly increased in trehalose-treated rats (p < 0.01). However, analysis of miR-34c expression level indicated no significant difference between trehalose-treated old rats and non-treated old animals (p > 0.05). Our results indicated that trehalose treatment improved learning and memory function in aged rats by targeting miR-181c. Therefore, trehalose administration may provide a therapeutic strategy to ameliorate age-associated cognitive impairment.

The Combination Effects of Resveratrol and Swimming HIIT Exercise on Novel Object Recognition and Open-field Tasks in Aged Rats.

INTRODUCTION: Resveratrol, a natural polyphenol abundant in grapes and red wine, has been reported to exert numerous beneficial health effects in the body. High-Intensity Interval Exercise (HIIT) is a form of interval training that provides improved athletic capacity and has a protective effect on health. The purpose of this study was to investigate the interactive effects of swimming HIIT and Resveratrol supplementation on behavioral function in Novel object recognition and open-field tests in aged rats. METHODS: A total of 45 aged male Wistar rats with an age of 20 months were randomly assigned into five groups of control (C), swimming HIIT (SW-HIIT), swimming HIIT with Resveratrol supplementation (SW-HIIT-R), Resveratrol supplementation (R), and solvent of Resveratrol supplementation (SR). There was also another group that included young animals (2-month-old) and was used to compare with older animals. Swimming HIIT and Resveratrol supplementation groups performed the exercise and received Resveratrol (10 mg/kg/day, gavage) for six weeks. Novel object recognition and open-field tests were used for evaluating the behavioral functions in animals. RESULTS: The results showed that HIIT and Resveratrol significantly improved recognition memory compared to old animals. Moreover, it seems that HIIT and Resveratrol partly could modulate anxiety-like behaviors compared to old animals in the open-field test.

The effects of high intensity exercise on learning and memory impairments followed by combination of sleep deprivation and demyelination induced by etidium bromide.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Cognitive impairments occurs in MS patients including learning and memory impairments. More than 50% of MS patients suffer from sleep problems. It has been suggested that in animal models exercise has direct neuroprotective effects on MS and sleep deprivation (SD). In this research, MS impairments were induced using a demyelination model as an indicator of MS disease. Also induction of SD was done using multiple platform. In order to focus on the research question, combination of MS model with SD was studied. In this study, the impact of treadmill exercise on learning and memory impairments was investigated. Material and methods: Male wistar rats were used in the present study. Exercise groups exercised daily for 1 h/day for 10 consecutive days with treadmill (speed: 18 m/min and inclination: 25°). The multiple platform method was applied for the induction of a 72 h SD. The cognitive functions were evaluated using Morris water maze (MWM) and open field tests. Animals were anaesthetized with a certain dose of ketamine and xylazin. After full anesthesia, the rat was placed on rat stereotaxic instrument in the skull-flat position. Demyelination was induced bilaterally by direct single injection of 3 µl of 0.01% ethidium bromide in sterile 0.9% saline at the rate of 1 µl/min into the hippocampal formation. The dose was injected using appropriate stereotaxic coordinates. Results: All of the learning and memory indices in the MWM task showed that SD and hippocampal demyelination destroy learning and memory. It seems that exercise can modulate the destructive effects of SD and demyelination on learning and memory at the behavioral level.

The effect of high-intensity interval training on type 2 diabetic muscle: A metabolomics-based study.

Background: This study aimed to investigate the effect of eight weeks of high-intensity interval training (HIIT) on muscle metabolism in rats with type 2 diabetes (T2D) using metabolomics approaches. Methods: 20 male Wistar rats at the age of 8 weeks-were assigned to four groups of five, each in the group randomly: control (CTL), type 2 diabetes (DB), HIIT (EX), and type 2 diabetes + HIIT (DBX). T2D was induced by two months of a high-fat diet plus a single dose of streptozotocin (35 mg/kg). Rats in the EX and DBX groups performed eight weeks of HIIT (running at 80-100 % of Vmax, 4-10 intervals). NMR spectroscopy was used to determine the changes in the muscle metabolome profile after training. Results: Changes in metabolite abundance following exercise revealed distinct clustering in multivariate analysis. The essential metabolite changes between the DB and CTL groups were arginine metabolism, purine metabolism, phosphate pathway, amino sugar metabolism, glutathione metabolism, and aminoacyl-tRNA biosynthesis. However, Arginine biosynthesis, pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism were altered between the DBX and DB groups. Conclusion: These results suggest that eight weeks of HIIT could reverse metabolic changes induced by T2D in rat muscles, contributing to reduced FBG and HOMA-IR levels.

An Updated Comprehensive Review of Plants and Herbal Compounds with Antiasthmatic Effect.

Background: Asthma is a common disease with rising prevalence worldwide, especially in industrialized countries. Current asthma therapy with traditional medicines lacks satisfactory success, hence the patients' search for alternative and complementary treatments for their diseases. Researchers have conducted many studies on plants with antiallergic and antiasthmatic effects in recent decades. Many of these plants are now used in clinics, and searching for their mechanism of action may result in creating new ideas for producing more effective drugs. Purpose: The goal of this review was to provide a compilation of the findings on plants and their active agents with experimentally confirmed antiasthmatic effects. Study Design and Method. A literature search was conducted from 1986 to November 2023 in Scopus, Springer Link, EMBASE, Science Direct, PubMed, Google Scholar, and Web of Science to identify and report the accumulated knowledge on herbs and their compounds that may be effective in asthma treatment. Results: The results revealed that 58 plants and 32 herbal extracted compounds had antiasthmatic activity. Also, 32 plants were shown to have anti-inflammatory and antioxidative effects or may act as bronchodilators and potentially have antiasthmatic effects, which must be investigated in future studies. Conclusion: The ability of herbal medicine to improve asthma symptoms has been confirmed by clinical and preclinical studies, and such compounds may be used as a source for developing new antiasthmatic drugs. Moreover, this review suggests that many bioactive compounds have therapeutic potential against asthma.

ATP releasing channels and the ameliorative effects of high intensity interval training on diabetic heart: a multifaceted analysis.

Type 2 diabetes (T2D) can cause severe cardiac complications at functional, histologic and molecular levels. These pathological complications could be mediated by ATP-releasing channels such as Panx1 and ATP receptors, in particular P2X7. The aim of our study was to investigate the effect of high-intensity interval training (HIIT) on T2D-induced cardiac complications at the functional, histopathological and molecular levels, with a particular focus on ATP-releasing channels. 48 male Wistar rats at the age of 8 weeks were randomly allocated into four groups: control (Con), Diabetes (T2D), Training (TR), and Diabetes + Training (T2D + TR). T2D was induced by a high-fat diet plus a low dose (35 mg/kg) of STZ administration. Rats in the TR and T2D + TR groups underwent an 8-weeks training program involving intervals ranging from 80 to 100% of their maximum running speed (Vmax), with 4-10 intervals per session. Protein expression of Interleukin 1ß (IL1ß), Interleukin 10 (IL-10), Pannexin 1 (Panx1), P2X7R (purinergic P2X receptor 7), NLRP1 (NLR Family Pyrin Domain Containing 1), BAX, and Bcl2 were measured in the heart tissue. Additionally, we assessed heart function, histopathological changes, as well as insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR). In contrast to the T2D group, HIIT led to increased protein expression of Bcl2 and IL-10 in the heart. It also resulted in improvements in systolic and diastolic blood pressures, heart rate, ± dp/dt (maximum and minimum changes in left ventricular pressure), while reducing protein expression of IL-1ß, Panx1, P2X7R, NLRP1, and BAX levels in the heart. Furthermore, left ventricular diastolic pressure (LVDP) was reduced (P ≤ 0.05). Moreover, heart lesion scores increased with T2D but decreased with HIIT, along with a reduction in fibrosis percentage (P ≤ 0.05). The results of this study suggest that the cardioprotective effects of HIIT on the diabetic heart may be mediated by the modulation of ATP-releasing channels. This modulation may lead to a reduction in inflammation and apoptosis, improve cardiac function, and attenuate cardiac injury and fibrosis.

Myrtenol ameliorates inflammatory, oxidative, apoptotic, and hyperplasic effects of urethane-induced atypical adenomatous hyperplasia in the rat lung.

Lung atypical adenomatous hyperplasia (AAH) is a forerunner of pulmonary adenocarcinoma. The drugs being utilized in the remediation of this type of hyperplasia have some adverse impacts. The present research focused on the potential anti-hyperplasia effect of myrtenol, an herbal terpenoid, on urethane-induced lung AAH in rats. Rats were injected with urethane (1.5 g/kg) thrice at 48 h intervals, and 20 weeks later, the animals were treated with 50 mg/kg myrtenol intraperitoneally once a day for 1 week. The ELISA method was used to measure inflammatory cytokines and oxidative parameters in the lung tissue and bronchoalveolar lavage fluid (BALF). The expression of NFκB and apoptotic/antiapoptotic factors (P53/Bcl-2) was evaluated by western blot and immunohistochemistry, respectively. H&E staining was performed for histopathological investigation. Histopathology confirmed the anti-hyperplasia effect of myrtenol, which was evidenced by the reduction of bronchoalveolar wall thickness and inflammation score. It also decreased hyperplasia progression by reducing Bcl-2, IL-10, p53, and Ki67. Compared with the urethane group, myrtenol normalized the activity of the oxidative stress markers malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Moreover, it showed an anti-inflammatory effect by decreasing lung and BALF IL-1ß levels and NFκB expression. Myrtenol may have a promising effect on lung cancer treatment by counteracting lung hyperplasia via modulation of inflammation, oxidative stress, and apoptosis.

Preparation and Evaluation of Preventive Effects of Inhalational and Intraperitoneal Injection of Myrtenol Loaded Nano-Niosomes on Lung Ischemia-Reperfusion Injury in Rats.

INTRODUCTION: Ischemia-reperfusion injury (IRI) is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled and intraperitoneal niosomal form, compared to its simple form, on lung ischemia reperfusion injury (LIRI). MATERIAL AND METHOD: Wistar rats were divided into ten groups. Simple and niosomal forms of myrtenol were inhaled or intraperitoneally injected daily for one week prior to LIRI. We evaluated oxidative stress, apoptotic, and inflammatory indices, nitric oxide, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and histopathological indices. RESULTS: Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the indices of pulmonary edema, pro-inflammatory cytokines and proteins, oxidant agents, nitric oxide, iNOS, apoptotic proteins, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli. Furthermore, myrtenol increased anti-inflammatory cytokines, anti-oxidants agents, eNOS, anti-apoptotic proteins and the survival time of animals. The niosomal form of myrtenol showed a more ameliorative effect than its simple form. CONCLUSION: The results showed the superior protective effect of the inhalation of myrtenol niosomal form against LIRI compared to its simple form and systemic use.

Myrtenol Inhalation Mitigates Asthma-Induced Cognitive Impairments: an Electrophysiological, Behavioral, Histological, and Molecular Study.

Asthma is an inflammatory disorder with significant health problems. It generally affects the lungs but can also impact brain performance via several mechanisms. Some investigations have proposed that asthma impairs cognition. This study assessed the impacts of myrtenol as a monoterpene on cognitive disorders following asthma at behavioral, molecular, and synaptic levels. Asthma was induced by injection and inhalation of ovalbumin (OVA). Male Wistar rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Myrtenol (8 mg/kg) or budesonide (160 µg/kg) was administered through inhalation once a day for 1 week, and at the end of the inhalation period, behavioral tests (MWM and Open Field), field potential recording, hippocampal brain-derived neurotrophic factor (BDNF), IL1ß (ELISA), and NFκB measurement (Western blot) were performed to evaluate cognitive performance. Moreover, H&E (hematoxylin and eosin) staining was used for hippocampus histological evaluation. Myrtenol improved spatial learning, memory, LTP (long-term potentiation) impairments, and anxiety-like behaviors following asthma. Myrtenol inhalation increased the BDNF level and decreased the IL1ß level and NFκB expression in the hippocampus of the asthmatic rats. The neuronal damage in the hippocampus following allergic asthma was alleviated via myrtenol administration. Myrtenol, as an herbal extract, protects the hippocampus from asthma consequences. Our observations revealed that myrtenol can improve spatial learning, memory, synaptic plasticity impairments, and anxiety-like behaviors following asthma. We believe that these ameliorating effects of myrtenol can be attributed to inflammation suppression and increased BDNF in the hippocampus.

The Diabetic Lung Can Be Ameliorated by Citrullus colocynthis by Reducing Inflammation and Oxidative Stress in Rats with Type 1 Diabetes.

Background: Diabetes impacts various organs in the body and some reports showed that the lung is also affected by diabetes, and an imbalance of inflammation and oxidative stress may participate to diabetic lung impairments. The present study is conducted to assess the impacts of Citrullus colocynthis (CC) on some aspects of these impairments. Methods: Frothy two male Wistar rats (3-4 months old and weighing 200-250 g) were used in the present research. Animals were divided into 3 groups of control, Diabetes, and Diabetes + Drug. CC was administered to diabetic rats orally. The lung tissue and BALF oxidative stress and inflammatory indices including the MDA, TAC, SOD, Gpx, TNFα, IL-6, IL-17, and IL-10 were evaluated by the ELISA method. Results: Our observations disclosed the ameliorative impacts of CC administration against oxidative stress and inflammation imbalance. Also, it was found that CC improved body weight and fasting blood sugar in rats with diabetes. Conclusion: We can conclude that the administration of CC can be effective in improving diabetic lungs in rats.

Adiponectin receptor 1 could explain the sex differences in molecular basis of cognitive improvements induced by exercise training in type 2 diabetic rats.

Adipokines dysregulation, the main reason for cognitive impairments (CI) induced by diabetes, shows a sex-dependent pattern inherently and in response to exercise. This study aimed to compare the attenuating effect of 8-week high intensity-interval training (HIIT) on type 2 diabetes (T2D)-induced CI between male and female rats with a special focus on adiponectin and leptin. 28 male & 28 female Wistar rats with an average age of 8 weeks were randomly assigned into four groups: control (Con), exercise (EX), Diabetes (T2D), and Type 2 diabetes + exercise (T2D + Ex). Rats in EX and T2D + EX groups performed HIIT for eight weeks (80-100% Vmax, 4-10 intervals). T2D was induced by 2 months of a high-fat diet and a single dose of STZ (35 mg/kg) administration. Leptin and adiponectin levels in serum were measured along with hippocampal expression of leptin and adiponectin receptors, AMP-activated protein kinase (AMPK), dephosphorylated glycogen synthase kinase-3 beta (Dep-GSK3ß), Tau, and beta-amyloid (Aß). Homeostasis model assessments (HOMAs) and quantitative insulin-sensitivity check index (QUICKI) indices were calculated. Our results showed that following T2D, serum levels of APN, and hippocampal levels of adiponectin receptor 1 (APNR1) were higher and HOMA-IR was lower in female than male rats (P < 0.05). However, after 8 weeks of HIIT, hippocampal levels of APNR1 and AMPK as well as QUICKI were lower and hippocampal levels of GSK, Tau, and Aß were higher in females compared to male rats (P < 0.05). While the risk of CI following T2D was more in male than female rats HIIT showed a more ameliorating effect in male animals with APN1 as the main player.