Neuroprotective properties of Betulin, Betulinic acid, and Ursolic acid as triterpenoids derivatives: a comprehensive review of mechanistic studies.

Cognitive deficits are the main outcome of neurological disorders whose occurrence has risen over the past three decades. Although there are some pharmacologic approaches approved for managing neurological disorders, it remains largely ineffective. Hence, exploring novel nature-based nutraceuticals is a pressing need to alleviate the results of neurodegenerative diseases, such as Alzheimer's disease (AD) and other neurodegenerative disorders. Some triterpenoids and their derivates can be considered potential therapeutics against neurological disorders due to their neuroprotective and cognitive-improving effects. Betulin (B), betulinic acid (BA), and ursolic acid (UA) are pentacyclic triterpenoid compounds with a variety of biological activities, including antioxidative, neuroprotective and anti-inflammatory properties. This review focuses on the therapeutic efficacy and probable molecular mechanisms of triterpenoids in damage prevention to neurons and restoring cognition in neurodegenerative diseases. Considering few studies on this concept, the precise mechanisms that mediate the effect of these compounds in neurodegenerative disorders have remained unknown. The findings can provide sufficient information about the advantages of these compounds against neurodegenerative diseases.

Inhibition of TLR4, NF-κB, and INOS pathways mediates ameliorative effect of syringic acid in experimental ulcerative colitis in rats.

OBJECTIVE: Numerous therapeutics and pharmacological properties have been reported in syringic acid (SA). In this study, we aimed to evaluate effect of SA in ulcerative colitis (UC) in rats considering effect on TLR4, NF-κB, and INOS pathways. MATERIALS AND METHODS: 48 Wistar rats were randomly designated into six groups (n = 8). UC was induced via intra-rectal administration of 7% acetic acid (0.8 ml). SA at doses of 10, 25, 50 mg/kg was administrated through gavage, and dexamethasone (2 mg/kg) administrated intra-peritoneally for 5 consecutive days. The macroscopic and histopathological damages as well as expression of inflammatory and apoptotic genes along with superoxide dismutase (SOD) and catalase (CAT) activities, total antioxidant capacity (TAC), nitric oxide (NO), and malondialdehyde (MDA) levels in the colon tissue were assessed. RESULTS: UC led to an increase in the apoptotic and inflammatory genes, NO and MDA levels as well as decrease in TAC level, and SOD and CAT activities (p < 0.05). UC also caused severe damage, edema, inflammation, and necrosis in the colon. SA significantly reduced gene expressions of INOS, TLR4, IL-6, IL-1ß, NF-κB, Caspase-3, Caspase-8, and Bax. SA ameliorated negative macroscopic and histopathologic effects of UC. SA significantly reduced MDA and NO levels, and increased TAC level and CAT activity in the colon tissue in comparison to the UC rats without treatment (p < 0.05). CONCLUSION: SA via attenuation of the TLR4-NF-κB, NF-κB-INOS-NO pathways, oxidative stress, inflammation, and apoptosis of UC in rats.

Design, synthesis, and characterization of novel system xC- transport inhibitors: inhibition of microglial glutamate release and neurotoxicity.

Neuroinflammation appears to involve some degree of excitotoxicity promulgated by microglia, which release glutamate via the system xC- (SxC-) cystine-glutamate antiporter. With the aim of mitigating this source of neuronal stress and toxicity, we have developed a panel of inhibitors of the SxC- antiporter. The compounds were based on L-tyrosine, as elements of its structure align with those of glutamate, a primary physiological substrate of the SxC- antiporter. In addition to 3,5-dibromotyrosine, ten compounds were synthesized via amidation of that parent molecule with a selection of acyl halides. These agents were tested for the ability to inhibit release of glutamate from microglia activated with lipopolysaccharide (LPS), an activity exhibited by eight of the compounds. To confirm that the compounds were inhibitors of SxC-, two of them were further tested for the ability to inhibit cystine uptake. Finally, these agents were shown to protect primary cortical neurons from the toxicity exhibited by activated microglia. These agents may hold promise in reducing the neurodegenerative effects of neuroinflammation in conditions, such as encephalitis, traumatic brain injury, stroke, or neurodegenerative diseases.

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.

Associations between empirically derived dietary patterns and oxidative stress and inflammation in adults with primary hypothyroidism: a case-control study.

BACKGROUND: Primary hypothyroidism is a common endocrine disorder caused by impaired production of thyroid hormones. Recent studies have shown that dietary habits, oxidative stress, and inflammation may play roles in thyroid hypofunction. Thus, the present article aimed to determine the relationship between major dietary patterns and oxidative stress and inflammation in primary hypothyroid patients and healthy people in Iranian adults. METHODS: This matched case-control study was conducted on 200 participants (100 cases and 100 controls). The presence of primary hypothyroidism was determined by endocrinologists based on American Thyroid Association (ATA) criteria. Dietary intake was assessed using a validated 168-item, semi-quantitative food frequency questionnaire (FFQ). The principal component analysis (PCA) method was used to derive major dietary patterns. Statistical analysis was performed using logistic regression analysis, and the findings were reported using odds ratios (ORs) with 95% CIs. RESULTS: We identified 2 major dietary patterns (i.e., healthy and Western dietary patterns). After adjusting for confounding variables, participants in the highest tertile of the healthy eating pattern had lower odds of primary hypothyroidism. Also, there was a significant relationship between total antioxidant capacity (TAC) levels and thyroid hypofunction; however, no significant correlation was seen between the Western dietary pattern and malondialdehyde (MDA) and C-reactive protein (CRP) with hypothyroidism. CONCLUSIONS: There were statistically direct associations between healthy dietary patterns (loaded with vegetables, nuts and seeds, fruits, dried fruits, olives, garlic, black pepper, starchy vegetables, low-fat dairy, and legumes) and increased TAC levels with a decreased risk of thyroid hypofunction. However, Western dietary patterns and MDA and CRP levels did not associate with an underactive thyroid.

Diabetes as one of the long-term COVID-19 complications: from the potential reason of more diabetic patients' susceptibility to COVID-19 to the possible caution of future global diabetes tsunami.

According to recent researches, people with diabetes mellitus (type 1 and 2) have a higher incidence of coronavirus disease 2019 (COVID-19), which is caused by a SARS-CoV-2 infection. In this regard, COVID-19 may make diabetic patients more sensitive to hyperglycemia by modifying the immunological and inflammatory responses and increasing reactive oxygen species (ROS) predisposing the patients to severe COVID-19 and potentially lethal results. Actually, in addition to COVID-19, diabetic patients have been demonstrated to have abnormally high levels of inflammatory cytokines, increased virus entrance, and decreased immune response. On the other hand, during the severe stage of COVID-19, the SARS-CoV-2-infected patients have lymphopenia and inflammatory cytokine storms that cause damage to several body organs such as ß cells of the pancreas which may make them as future diabetic candidates. In this line, the nuclear factor kappa B (NF-κB) pathway, which is activated by a number of mediators, plays a substantial part in cytokine storms through various pathways. In this pathway, some polymorphisms also make the individuals more competent to diabetes via infection with SARS-CoV-2. On the other hand, during hospitalization of SARS-CoV-2-infected patients, the use of some drugs may unintentionally lead to diabetes in the future via increasing inflammation and stress oxidative. Thus, in this review, we will first explain why diabetic patients are more susceptible to COVID-19. Second, we will warn about a future global diabetes tsunami via the SARS-CoV-2 as one of its long-term complications.

Adherence to the Mediterranean Diet Association with Serum Inflammatory Factors Stress Oxidative and Appetite in COVID-19 Patients.

Background and Objectives: The Mediterranean diet's bioactive components are suggested to strengthen the immune system and to exert anti-inflammatory actions. This study investigated the association between adherence to the Mediterranean diet with serum inflammatory factors, total antioxidant capacity, appetite, and symptoms of COVID-19 patients. Materials and Methods: This cross-sectional study was conducted among 600 Iranian COVID-19 patients selected by a simple random method. The ten-item Mediterranean diet adherence questionnaire was used to assess diet adherence. At the beginning of the study, 5 cc of blood was taken from all patients for measurement of serum interleukin 1ß) IL-1ß), tumor necrosis factor (TNF-α), malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP) and total antioxidant capacity (TAC). A human ELISA kit with serial number 950.090.096 produced by the Diaclone Company was used to test this cytokine using the sandwich ELISA method. Results: One hundred and five patients presented a high adherence and 495 patients presented a low adherence to the Mediterranean diet. The incidence of fever, cough, diarrhea, taste changes, and pneumonia severity index were significantly lower in patients who adhered to the Mediterranean diet more than other patients. Serum levels of tumor necrosis factor (5.7 ± 2.1 vs. 6.9 ± 2.8 p = 0.02), interleukin 1 beta (3.2 ± 0.02 vs. 4.9 ± 0.01 p = 0.02), high-sensitivity C-reactive protein (17.08 ± 4.2 vs. 19.8 ± 2.5 p = 0.03), and malondialdehyde (5.7 ± 0.2 vs. 6.2 ± 0.3 p = 0.02) were significantly lower in patients who adhered more to the Mediterranean diet than other patients. Conclusion: The Mediterranean diet can improve the symptoms and elevated serum inflammatory factors in COVID-19 patients, so clinical trial studies are suggested to confirm this effect.

Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury.

BACKGROUND: Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. METHODS: First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. RESULTS: Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1ß (IL-1ß) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. CONCLUSION: Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

Significant reduction of long non-coding RNAs expression in bipolar disorder.

Long non-coding RNAs (lncRNAs) have been recently emerged as critical modulators of oxidative stress pathway. Likewise, rising evidence currently highlights dysfunction of oxidative stress pathways in bipolar disorder (BD) patients.In the current study, we evaluated the expression levels of H19, SCAL1 (LUCAT1), RMST, MEG3 and MT1DP lncRNAs in the PBMC from 50 patients with BD and 50 control subjects (male/female ratio in each group: 70%/30%). Expression levels of SCAL1, RMST and MEG3 but not H19 and MT1DP were considerably decreased in BD patients compared with healthy individuals. Such significant decrease in the expression of MEG3, RMST and SCAL1 was only reported in male BD patients compared with male controls. Substantial pairwise correlations were observed between expression levels of these lncRNAs in BD subjects. The area under curve values for RMST, MEG3 and SCAL1 were 0.70, 0.63 and 0.61 respectively. On the basis of this finding, RMST had the best efficiency in the discrimination of disease status between BD patients and controls. Taken together, the current results suggest a role for MEG3, RMST and SCAL1 lncRNAs in the pathogenesis of BD. In addition, peripheral expression levels of these lncRNAs might serve as potential peripheral markers for BD.

The comparison of the effect of Origanum vulgare L. extract and vitamin C on the gentamycin-induced nephrotoxicity in rats.

The gentamicin renal toxicity has been the focal point for much discussion. The objective of this study was to investigate the impacts of Origanum vulgare L. extract and vitamin C on gentamicin dose-dependent toxicity in rats' kidney. The present study was conducted on 60 male Wistar rats divided into ten experimental groups: control (untreated), G1, G2, G3 (100, 200, 300 mg/kg gentamicin), M1, M2 and M3 (500 mg/kg marjoram extract) + 100, 200 and 300 gentamicin, V1, V2 and V3 (Vitamin C 500 mg/kg) + 100, 200 and 300 of gentamicin. On the last day, the serum was separated from heart blood and the kidney tissues were extracted to measure the biochemical and oxidative stress parameters and histological changes. Kidney damage was confirmed as dose-dependent gentamicin by biochemical and pathological parameters. Urea, Blood Urea Nitrogen (BUN), and creatinine showed a significant increase in the G3 group compared to the control, M1, and V1 groups (p < 0.01). Catalase (CAT), Glutathione peroxidase (GPx), and Superoxide dismutase (SOD) showed a significant reduction in renal tissue in the G3 group compared to the other groups (p < 0.001). Malondialdehyde (MDA) concentration in the kidney tissue of the G3 group also showed a significant increase compared to other groups (p < 0.001). Furthermore, TNFα and IL-1 levels were the highest in the G3 group, and serum total antioxidant capacity (TAC) concentration had the lowest amount compared to other groups. Moreover, histopathological lesions of the kidney showed significant statistical differences among the groups that received gentamicin with the control and M1 group. Marjoram extract at the dose of 500 mg/kg had a desirable effect on controlling gentamicin damage in the kidneys compared with vitamin C. In particular, controlling gentamicin-induced oxidative stress and inflammation by the consumption of marjoram extract and vitamin C plays an important role in protecting the kidneys.

Randomized double-blind clinical trial examining the Ellagic acid effects on glycemic status, insulin resistance, antioxidant, and inflammatory factors in patients with type 2 diabetes.

Oxidative stress can worsen glycemic status. Considering the antioxidant properties of Ellagic acid (EA), this study was designed to evaluate the effect of EA on glycemic indices, lipid profile, oxidative stress, and inflammation status in type 2 diabetic patients. Overall, 44 patients were recruited and were randomly allocated consumed 180 mg of EA per day (n = 22) or placebo (n = 22) for 8 weeks. The blood sugar (BS), insulin, insulin resistance (IR), hemoglobin A1c (HbA1 c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total antioxidant capacity (TAC), malondialdehyde (MDA), the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), C-reactive protein (CRP), TNF-α and interleukin 6 (IL-6) were measured at the beginning and end of the study. At the end of the study, the mean of BS, insulin, IR, HbA1 c, TC, TG, LDL, MDA, CRP, TNF-α, and IL-6 were significantly decreased in the intervention group (p < .05). Also, the mean of TAC (+0.8 ± 0.01) and activity of GPx (+10.26 ± 0.22) and SOD enzymes (+459.6 ± 9.76) significantly increased in the intervention group (p < .05). EA supplementation can be helpful as a diet supplement in patients with type 2 diabetes through improvement in chronic adverse effects.

The ameliorating effects of Vitamin E on hepatotoxicity of ecstasy.

BACKGROUND: The production of stress oxidative condition in body which is caused by consumption of ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) leads to a liver damage. As an antioxidant, Vitamin E can protect cells and tissues against the deleterious effects of free radicals. This study evaluates the protective effects of Vitamin E on MDMA induced liver toxicity. MATERIALS AND METHODS: Twenty-eight male albino mice were randomly assigned to four equal groups. Group 1 received saline (control), Group 2 received MDMA and saline, Group 3 received MDMA, and Vitamin E and Group 4 received Vitamin E. MDMA was injected with single daily dose, three sequential days/week for 5 weeks. At the end of the period, blood samples were collected for a biochemical analysis and then the mice were sacrificed by cervical dislocation for histopathological and biochemical examinations of liver. RESULTS: The administration of Vitamin E attenuated the increased levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase enzymes in serum. Vitamin E treatments significantly restored endogenous antioxidant enzymes (reduced glutathione and superoxide dismutase enzyme) activities as compared with MDMA-treated animals. Histological examination of liver revealed significant morphological tissue injuries in hepatocytes after MDMA being used, but in coadministration of vitamin E and MDMA, these morphological alterations reduced. CONCLUSION: The study showed that MDMA administration has adverse effects on the liver. Vitamin E lessened the deleterious impact considerably.

Particulate Matter Exposure and Stress Hormone Levels: A Randomized, Double-Blind, Crossover Trial of Air Purification.

BACKGROUND: Exposure to ambient particulate matter (PM) is associated with a number of adverse health outcomes, but potential mechanisms are largely unknown. Metabolomics represents a powerful approach to study global metabolic changes in response to environmental exposures. We therefore conducted this study to investigate changes in serum metabolites in response to the reduction of PM exposure among healthy college students. METHODS: We conducted a randomized, double-blind crossover trial in 55 healthy college students in Shanghai, China. Real and sham air purifiers were placed in participants' dormitories in random order for 9 days with a 12-day washout period. Serum metabolites were quantified by using gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-mass spectrometry. Between-treatment differences in metabolites were examined using orthogonal partial least square-discriminant analysis and mixed-effect models. Secondary outcomes include blood pressure, corticotropin-releasing hormone, adrenocorticotropic hormone, insulin resistance, and biomarkers of oxidative stress and inflammation. RESULTS: The average personal exposure to PMs with aerodynamic diameters ≤2.5 µm was 24.3 µg/m3 during the real purification and 53.1 µg/m3 during the sham purification. Metabolomics analysis showed that higher exposure to PMs with aerodynamic diameters ≤2.5 µm led to significant increases in cortisol, cortisone, epinephrine, and norepinephrine. Between-treatment differences were also observed for glucose, amino acids, fatty acids, and lipids. We found significantly higher blood pressure, hormones, insulin resistance, and biomarkers of oxidative stress and inflammation among individuals exposed to higher PMs with aerodynamic diameters ≤2.5 µm. CONCLUSIONS: This study suggests that higher PM may induce metabolic alterations that are consistent with activations of the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes, adding potential mechanistic insights into the adverse health outcomes associated with PM. Furthermore, our study demonstrated short-term reductions in stress hormone following indoor air purification. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02712333.

Impact of intestinal mannitol on hyperammonemia, oxidative stress and severity of hepatic encephalopathy in the ED.

Hyperammonemia results from hepatic inability to remove nitrogenous products generated by protein metabolism of intestinal microbiota, which leads to hepatic encephalopathy (HE) in chronic liver disease (CLD). In ammonium neurotoxicity, oxidative stress (OxS) plays a pathogenic role. Our objective was to evaluate if intestinal mannitol is as effective and safe as conventional treatment for diminishing hyperammonemia, OxS, and HE in patients with CLD. MATERIAL AND METHODS: We included 30 patients with HE classified by "Haven Criteria for Hepatic Encephalopathy". They were randomized into two groups: 1) Mannitol Group (MG) with mannitol 20% administered into the intestine by an enema, 2) conventional group (CG) with lactulose 40 g enema both substances were diluted in 800 mL of double distilled solution every 6 h; all patients received neomycin. We evaluated ammonia concentration, plasma oxidative stress, HE severity, intestinal discomfort and adverse effects. RESULTS: Hyperammonemia (171 ±â€¯104 vs 79 ±â€¯49 µmol ammonia/L, p < 0.01), and oxidative stress (MDA 29 vs 27%, formazan 15 vs 11%, carbonyls 16 vs 9% and dityrosines 10 vs 5%) were reduced in MG and CG respectively. The HE severity decreased by two degrees compared to baseline values in both groups. Intestinal discomfort and electrolyte plasma alterations were less frequent (p < 0.05) in MG than CG. CONCLUSIONS: Intestinal mannitol is as effective and safe as conventional treatment for reducing hyperammonemia, oxidative stress, and hepatic encephalopathy of CLD patients in the emergency room. Likewise, mannitol is better tolerated than conventional treatment.

Overview of Nrf2 as Therapeutic Target in Epilepsy.

Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2), which plays a central role in the regulation of antioxidant response elements (ARE) and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy.

Comparative Effect of Chemical and Green Zinc Nanoparticles on the Growth, Hematology, Serum Biochemical, Antioxidant Parameters, and Immunity in Serum and Mucus of Goldfish, Carassius auratus (Linnaeus, 1758).

Recently, nano feed supplement research has great attention to improving healthy aquatic production and improving the aquatic environment. With the aims of the present study, chemical and green synthesized nanoparticles are characterized by various instrumentation analyses, namely UV-Vis spectrophotometry (UV-Vis), X-ray diffraction (XRD), Fourier transform infra-red (FTIR) spectroscopy, and scanning electron microscope (SEM). After characterization analysis of these nanoparticles utilized in aquatic animals, the composition ratio is as follows: controls (without ZnO-NPs (0 mg/L)), T1 (0.9 mg/L ZnO-NPs), T2 (1.9 mg/L ZnO-NPs), T3 (0.9 mg/L GZnO-NPs), T4 (1.9 mg/L GZnO-NPs). SEM investigation report demonstrates that the structure of the surface of green synthesized zinc oxide nanoparticles (GZnO-NPs) was conical shape and the size ranging was from 60 to 70 nm. Concerning hematological parameters, the quantity of hemoglobin increased in different doses of green zinc nanoparticles, but the values of MCV and MCH decreased somewhat. However, this decrease was the highest in the T2 group. Total protein and albumin decreased in T2 and triglyceride, cholesterol, glucose, cortisol, creatinine, and urea increased, while in T3 and T4 groups, changes in biochemical parameters were evaluated as positive. Mucosal and serum immunological parameters in the T2 group showed a significant decrease compared to other groups. In zinc nanoparticles, with increasing dose, oxidative damage is aggravated, so in the T2 group, a decrease in antioxidant enzymes and an increase in MDA were seen compared to other groups. In this regard, the concentration of liver enzymes AST and ALT increased in the T2 group compared with control and other groups. This can confirm liver damage in this dose compared with control and other groups. This research work suggests that green synthesized form of zinc nanoparticles in higher doses have less toxic effects in comparison to the chemical form of zinc nanoparticles and can act as suitable nutrient supplements in aquatic animals.

The oxidative stress-associated long non-coding RNAs in pancreatic cancer.

PURPOSE: A lot of people are dying from pancreatic cancer (PC) annually. The early detection of this cancer is particularly challenging due to the fact that symptoms tend to appear in advanced stages. It has been suggested that oxidative stress may play a role in the development of PC. Several genes regulate this process, including long noncoding RNAs (lncRNAs). There is no comprehensive study on the expression pattern of lncRNAs related to oxidative stress in PC patients. In the present case-control study, we quantified levels of oxidative stress-associated lncRNAs in PC patients versus healthy controls. PATIENTS AND METHODS: In the present study, we investigated the expression levels of lincRNA-p21, LUCAT, RMST, FOXD3-AS1, and MT1DP lncRNAs in the peripheral blood mononuclear cells (PBMCs) of 53 â€‹PC patients and 50 healthy controls. The association between lncRNA expression and clinical and pathological characteristics was also evaluated. RESULTS: The expression of lincRNA-P21 and rhabdomyosarcoma 2-associated transcript (RMST) lncRNAs in PC patients has significantly decreased. Expression of lncRNA RMST was significantly higher in TNM stage III-IV patients in comparison to TNM stage I-II patients. In addition, a significant positive association was recognized between candidate lncRNA expression, and finally, the AUC values of the expression levels of lincRNA-p21 and RMST were 0.60 and 0.61, respectively. CONCLUSIONS: Altogether, our study suggests a possible role of lincRNA-p21 and RMST lncRNAs in the etiology of PC pathobiology, and their biomarker role may be understood in future studies.

Efficacy of melatonin in alleviating disorders arising from repeated exposure to sevoflurane in males and females of the Wistar rats during preadolescence.

Pediatricians use sevoflurane due to its fast action and short recovery time. However, studies have shown that repeated exposure to anesthesia can affect learning and memory. Melatonin, an indole-type neuroendocrine hormone, has significant anti-inflammatory, and neuroprotective properties. Melatonin's impact on cognitive behavior in sevoflurane-anesthetized males and females of the Wistar rats during preadolescence was examined in this research. The cognitive function was evaluated by shuttle box and morris water maze tests, while interleukin-10, Catalase (CAT), Malondialdehyde (MDA), and Tumor Necrosis Factor-α (TNF-α) were evaluated using ELISA kits. The expression levels of the apoptosis-linked proteins, Bax, Bcl-2, and caspase-3, were determined using the western blotting technique. The learning and memory latencies of the rats were more significant in the sevoflurane groups than in the control group; however, the latencies were significantly shorter in the sevoflurane and melatonin groups than in the control group. The levels of MDA, TNF-α, Bax, and caspase-3 were significantly higher in the sevoflurane groups than in the control group. We also found that the levels of CAT and Bcl-2 were significantly reduced in the sevoflurane groups compared to the control group. Increasing levels of CAT, Bcl-2, and decreasing levels of MDA, TNF-α, Bax, and caspase-3 in response to melatonin indicate a possible contribution to the recovery from the sevoflurane impairment. Melatonin shows neuroprotective effects in male and female rats with sevoflurane-induced cognitive impairment. This suggests melatonin could be a valuable treatment for learning and memory deficits resulting from repeated exposure to sevoflurane, possibly by controlling apoptosis, oxidative stress, and inflammation.

Radioprotective effect of Cerebrolysin in the Rat's Brain Tissues.

AIM: The aim of this study is to evaluate radioprotective effects of Cerebrolysin (CBL) in rats' brain tissues after local irradiation. BACKGROUND: CBL has demonstrated antioxidant, anti-inflammatory, and tissue repair properties. In this study, the radioprotective effects of CBL in the brain tissues of rats after Irradiation (IR) (50 mg/ kg) were evaluated. OBJECTIVE: The levels of different oxidative stress markers, including malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were examined after treatment with radiation and CBL. METHODS: First, 20 male adult Wistar rats weighing 180-200 g were used. The animals were exposed to a single fraction of 15Gy using a linear accelerator unit at a dose rate of 200 cGy/mine. In this study, to check the amount of oxidative stress following the IR, the level of four markers MDA, NO, GPx, CAT, and SOD were examined and measured using the spectrophotometric method and purchased kits. RESULTS: The results showed that compared to the IR group, the administration of CBL increases the levels of GPX and SOD significantly (p < 0.05). CONCLUSION: Our finding suggests that CBL has radioprotective effects on the brain by enhancing antioxidant defense mechanisms.

The Interactive Effects of The Aerobic Exercise and Vitamin E Supplementation on Parkinson's Rat Model.

OBJECTIVE: In Parkinson's disease (PD), mitochondrial defects and oxidative stress cause an increase in free radicals and the death of dopaminergic neurons in the substantia nigra. By preventing lipid peroxidation and protecting against peroxide radicals, vitamin E is the most important antioxidant of biological membranes that can neutralize free radicals. Also, the improvement of the functional status of mitochondria can be influenced by exercise, which can be partially the result of changes in the mitochondrial mitophagy and dynamics system. This study aimed to investigate the interactive effects of six weeks of vitamin E (VE) consumption and training on the mitochondrial function [Cytochrome C (Cyt-C), Adenosine triphosphate (Atp) synthase, optical atrophy1 mitochondrial dynamics like guanosine triphosphatase (GTPase), 8-Oxodequanosin and Pten induced kinase 1 (Pink1) is a protein coding gene] in the hippocampus tissue of PD rats. MATERIALS AND METHODS: In this experimental study, 4-6-month-old Sprague-Dawley rats (mean weight 250 ± 30 g) were given parkinsonism with reserpine (2 mg/kg) and were categorized into different groups, including healthy (H), PD, VE solvent+PD (Sham), aerobic exercise+PD (AE+PD), VE+PD, AE+VE+PD. The aerobic training program was carried out for six weeks and 5 sessions per week and each session lasted 15-22 minutes. VE was also taken orally at 30 mg/kg daily. RESULTS: A six-week regimen of VE supplement along with the AE significantly reduced the Cyt-C gene expression level, also we observed a significant increase in gene expression level of the Pink1, Atp synthase and Opa1 (P<0.05). There is no significant difference was found in the level of 8-Oxog detected in hippocampal tissue samples (P>0.05). CONCLUSION: The consumption of VE along with AE may provide therapeutic effects on mitochondrial damage in PD rats.