Ameliorating Effects of Bioactive Peptides Extracted from Litopenaeus vannamei Wastes on Oxidative Stress, Glucose Regulation, and Autophagy Gene Expression in Nonalcoholic Fatty Liver-Induced Rats.

This study aimed to investigate the effect of bioactive peptides from Litopenaeus vannamei on oxidative stress, glucose regulation, and autophagy gene expression in the induced nonalcoholic fatty liver rats. Bioactive peptides used in the current study were extracted in a progressive rise in temperature (40-60°C) (GP). For this purpose, twenty-four healthy male rats (initial weight, 230.1 ± 22 g) were divided in four experimental groups including control (standard diet), HFD (high-fat diet), HFD + GP20, and 300 (high-fat diet + 20, 300 mg peptides/kg body weight). After 70 days, the results indicated that experimental treatments did not affect the body and liver weight (P > 0.05), although the higher liver weight was seen in HFD treatment. Based on these results, the use of GP peptides improved antioxidant enzymes and decreased MDA concentration, and a significant difference was observed between peptide treatments and HFD (P < 0.05). In comparison to the HFD group, significantly lower liver enzymes (ALT and AST) were seen in peptide treatments (P < 0.05). Also, the results indicated that the lowest amylase, alkaline phosphatase, glucose, insulin, HOMA-IR, and inflammation cytokines (TNF-ɑ and IL-6) were seen in peptide groups. The autophagy gene expression was measured in the liver cells, and the results showed that, unlike HFD treatment, the use of GP peptides decreased Beclin 1, Atg7, and P62 expression in male rat's livers. Overall, the results of the current study demonstrated that the use of GP peptides at low concentration shows significant hypoglycemia and antioxidant properties in nonalcoholic fatty liver-induced rats.

Improved Executive Functions and Reduced Craving in Youths with Methamphetamine Addiction: Evidence from Combined Transcranial Direct Current Stimulation with Mindfulness Treatment.

OBJECTIVE: Transcranial direct current stimulation (tDCS) and mindfulness practices have been proposed as a potential approach to improve executive functions (EFs) and reduce craving in persons with substance use disorders. Based on the neural mechanisms of action of each of these interventions, the combination of both non-pharmacological interventions might have additive effects. In the current study, the effects of tDCS combined with mindfulness-based substance abuse treatment (MBSAT) to improve EFs and reduce craving were investigated in early abstinent methamphetamine abuse. METHODS: Eighty (youths aged between 18 and 21) early-abstinent methamphetamine users were randomly assigned to the research groups (tDCS group [n = 20], mindfulness group [n = 20], combined mindfulness-tDCS group [n = 20], and sham group [n = 20]). Active tDCS (1.5 mA,20 min, 12 sessions) or sham tDCS was appliedover the left dorsolateral prefrontal cortex and the MBSAT protocol was used over twelve 50-min sessions. RESULTS: Both in the post-test phase (immediately after the intervention) and follow-up phase (one month after the intervention), performance in most EFs tasks significantly improved in the combination group which received real tDCS ＋ MBSAT, as compared to baseline values and sham stimulation group. Similarly, a significant reduction in craving was observed after intervention inall treatment groups, but not the sham stimulation group. Interestingly, the increase in EFs and the reduction in craving post versus pre tDCS ＋ MBSAT intervention were correlated. CONCLUSION: Findings from the current study provide initial support for the clinical effectiveness of combination tDCS ＋ MBSAT, possibly influencing cognitive/affective processes.

Balance-based Attentive Rehabilitation of Attention Networks (BARAN) improves executive functions and ameliorates behavioral symptoms in children with ADHD.

INTRODUCTION: Balance as a motor activity requires integrating different sensory information to maintain the center of gravity above the base of support through proper motor strategies in the light of cognitive processing. METHODS: In the present study, twenty-nine children with attention deficit- hyperactivity disorder (ADHD) were recruited in a random clinical trial design in two intervention and active control groups. The N-Back, Wisconsin Card Sorting, Go/No-Go tasks, and Conners' Teacher and Parent Rating Scales were performed in baseline, post-intervention, and follow-up sessions. The intervention group received balance-based attentive rehabilitation of attention (BARAN), and the active control group received aerobic exercise and running in 12-15 sessions. RESULTS: BARAN improves working memory (P < .05), cognitive flexibility (P < .01), and inhibitory control (P < .05) and ameliorates ADHD symptoms at home (P < .01) and school (P < .05). CONCLUSION: Dual-balance and cognitive tasks improve executive functions and ameliorate symptoms in children with ADHD.

Royal jelly protects male rats from heat stress-induced reproductive failure.

Royal jelly (RJ) as an antioxidant has been shown to have attenuated oxidative stress damages in reproductive organs. The objective was carried out the effects of RJ on sperm characteristics, sperm malondialdehyde (MDA) concentration and in vitro fertilisation (IVF) outcome in heat stress (HS) exposed male rats. Forty-eight male rats were randomly divided into eight groups; group 1 received normal saline, group 2 received RJ (100 mg kg-1  day-1 ; PO), groups 3, 4 and 5 were heat-stressed (43, 39 and 37°C for 20 min per day respectively) and groups 6, 7 and 8 were heat-stressed along with RJ (43, 39 and 37°C for 20 min per day, respectively, plus RJ at a dose of 100 mg kg-1  day-1 ; PO). The HS was induced through immersion of experimental rat scrotums in a water bath. After 48 days, the HS induced remarkable diminish in sperm motility, viability and fertilising potential along with reduced blastulation rate and enhanced sperm chromatin abnormality, MDA levels and DNA damage. Nevertheless, RJ co-administration improved sperm characteristics and early embryo development as well as sperm lipid peroxidation level. Our data suggest that RJ can effectively ameliorate the experimental HS-induced infertility in rats through MDA concentration restoration and sperm characteristics and pre-implantation embryo development improvement.

Selenium-Enriched Saccharomyces cerevisiae Reduces the Progression of Colorectal Cancer.

Colorectal cancer is one of the most common causes of mortality in the world while malnutrition is responsible for one third of the problem. Selenium has been recommended for prevention of colorectal cancer. The present study was conducted to investigate the effect of selenium-enriched Saccharomyces cerevisiae in reducing colorectal cancer progression in rats. Five groups of 170-200-g weight rats (n = 40) including healthy and cancer controls, Saccharomyces cerevisiae, selenium, and selenium-enriched Saccharomyces cerevisiae-treated groups were examined. All animals except healthy control group received 40 mg 1,2-dimethylhydrazine (DMH) per kilogram weight of rat twice a week. The healthy group received normal saline, and synchronously, selenium group received soluble selenium (4 mg/mL), Saccharomyces cerevisiae and selenium-enriched groups received yeast with the density of 5 × 108 CFU/mL by daily gavage. All treatments were carried out for 5 weeks after the last injection. Animals were autopsied, and aberrant crypt foci (ACF) of ejected colon were studied in the 40th week. Microscopic sections were prepared for hematoxylin and eosin. Furthermore, immunohistochemical staining of CD31, BCL2, and P53 antibodies was performed. Macroscopic and microscopic evaluations showed that DMH had the least destructive effect in selenium-enriched Saccharomyces cerevisiae group compared to other groups. Selenium-enriched Saccharomyces cerevisiae reduces colorectal cancer progression by various mechanisms such as reduction in the number and size of ACF and alteration in the function of the proteins such as P53, BCL2, and CD31.

Royal Jelly Promotes Ovarian Follicles Growth and Increases Steroid Hormones in Immature Rats.

BACKGROUND: Royal jelly (RJ) is a complementary diet widely prescribed by traditional medicine specialists for treatment of infertility. The aim of present study was to evaluate the effects of RJ on a set of reproductive parameters in immature female rats. MATERIALS AND METHODS: In this experimental study, thirty two immature female rats (30-35 g) were divided into four groups (n=8/group): three experimental groups and one control. The experimental groups received 100, 200 and 400 mg/kg/body weight doses of RJ daily for 14 days, and the control group received 0.5 ml distilled water interaperitonealy (i.p). The treated rats were sacrificed and their ovaries were dissected for histological examination. The serum levels of ovarian hormones, nitric oxide (NO) and ferric reducing antioxidant power (FRAP) were evaluated, and the ratios of the ovarian and uterine weight to body weight were calculated. One-way ANOVA was used for data analysis. RESULTS: The body weights were significantly different (P=0.002) among the rat groups, with an increase in all RJ treated animals. Uterine and ovarian weights and the serum levels of progesterone (P=0.013) and estradiol (P=0.004) were significantly increased in experimental groups compared to the control group. In addition, a significant increase in the number of mature follicles and corpora lutea (P=0.007) was seen in RJ recipients compared to the controls. A significant increase in the serum levels of FRAP (P=0.009) and a significant decrease in NO level (P=0.013) were also observed. CONCLUSION: RJ promotes folliculogensis and increases ovarian hormones. This product can be considered as a natural growth stimulator for immature female animals.

Ameliorative effect of omega-3 on spermatogenesis, testicular antioxidant status and preimplantation embryo development in streptozotocin-induced diabetes in rats.

PURPOSE: The present study was done to determine the ameliorative effect of polyunsaturated fatty acid omega-3 against experimental diabetes-induced damages on testicular tissue, sperm parameters and preimplantation embryo development in rat model. METHODS: Thirty-two mature male rats were divided into two control and test groups. The experimental diabetes (50 mg kg-1 streptozotocin, ip) was induced in test group and subdivided into non-treated diabetic, 300 and 600 mg kg-1 omega-3-treated (orally by gavage) groups. The rats in control group received 0.5 ml saline using intra-gastric gavage. Following 45 days, general histopathological changes, serum level of testosterone, inhibin B, glucose, and sperm parameters, testicular total antioxidant capacity (TAC) and malondialdehyde (MDA) content were analyzed. The mitochondria-dependent apoptosis was investigated by assessing the Bcl-2 and caspase-3 expression as well as DNA fragmentation. Finally, the in vitro fertilization (IVF) potential was examined by evaluating preimplantation embryo developing. RESULTS: The omega-3 significantly ameliorated the diabetes-induced histological damages, diminished serum level of glucose, testicular MDA content, and enhanced the serum testosterone, inhibin B and testicular TAC. The animals in omega-3-treated groups exhibited a significant (p < 0.05) up-regulation in Bcl-2, as well as remarkable (p < 0.05) down-regulation in caspase-3 expression compared to non-treated diabetic rats. Moreover, the omega-3 maintained DNA integrity, improved sperm quality as well as preimplantation embryo development. CONCLUSION: Our data showed that the omega-3 (especially at 600 mg kg-1 dose level) effectively ameliorates the experimental diabetes-induced infertility in rats by up-regulating the testicular endocrine and antioxidant statuses, preventing mitochondria-dependent apoptosis pathway and potentially improving the sperm quality.

Treatment of undifferentiated colorectal cancer cells with fish-oil derived docosahexaenoic acid triggers caspase-3 activation and apoptosis.

BACKGROUND: The effectiveness of chemotherapy is often limited by the side effects on normal tissues. Consequently, the search for new therapeutic agents with minimal toxicity is of particular interest in cancer management. Many studies have shown that docosahexaenoic acid (DHA) have cytotoxic effects against different kinds of cancer cells. However, little attention has been paid to explore the effect of DHA on undifferentiated colorectal cancer cells. In this study, the effects of DHA on LS174T cells as an early stage of tumor initiation were investigated. MATERIALS AND METHODS: Tumor cells were treated to various concentrations of DHA and proliferation, survivin expression, caspase-3 activation, and apoptosis were evaluated by different cellular and molecular techniques. RESULTS: Following 48 h treatment, proliferation was measured to be 73 ± 4.5% (P = 0.000), 53 ± 5.7% (P = 0.000) and 26.3 ± 3.5% (P = 0.000) for 50, 100, and 150 µM DHA, respectively compared to untreated cells. This molecule induced 63% (P = 0.001) and 46% (P = 0.000) decrease in survivin messenger ribonucleic acid (mRNA) level as well as 1.8 (P = 0.001) and three-fold (P = 0.000) increase in caspase-3 activation for 50 and 100 µM DHA, respectively compared to untreated cells. Our evidence showed that survivin mRNA is expressed at the early stage of colorectal cancer cells and DHA-treated cells expressed markedly a lower survivin mRNA compared to untreated cells. CONCLUSIONS: DHA is an attractive repressor of survivin expression, increases caspase-3 and apoptosis in colorectal cancer cells and may provide a novel approach to the treatment of colorectal cancer at the early stage of tumor initiation.

Treatment of LS174T colorectal cancer stem-like cells with n-3 PUFAs induces growth suppression through inhibition of survivin expression and induction of caspase-3 activation.

PURPOSE: Colorectal cancer stem cells (CCSCs) are thought to contribute to tumor initiation, progression, metastasis, chemo-resistance and therapy failure. Therefore, assessment of the effectiveness of agents with anti-proliferative activities against CCSCs is warranted. Several studies have shown that different tumorigenic steps, ranging from initiation to metastasis, can be affected by n-3 polyunsaturated fatty acids (PUFAs). Here, we evaluated the effects of the PUFA components docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), alone or in combination, on LS174T cells that serve as a model for colorectal cancer initiating cells with stem cell-like properties. METHODS: LS174T cells were treated with 50, 100 and 150 µM DHA and EPA, or equal mixtures of DHA/EPA (i.e., 25/25, 50/50 and 75/75 µM), after which cell number, viability, growth inhibition, survivin expression, caspase-3 activation and apoptotic rate were evaluated. RESULTS: We found that treatment of LS174T cells with increasing PUFA concentrations significantly increased growth inhibition in a dose- and time-dependent manner. After a 72 h treatment with 150 µM DHA and EPA, or their combination (75/75 µM), growth rates were inhibited by 80.3 ± 5.5%, 79.3 ± 5% and 71.1 ± 1%, respectively, compared to untreated cells. We also found that treatment for 48 h with 100 µM DHA and EPA, or their combination (50/50 µM), resulted in 2.9-, 3- and 2.6-fold increases in caspase-3 activation, as well as 54, 62.4 and 100% decreases in survivin mRNA expression levels, respectively, compared to untreated cells. Low survivin mRNA levels combined with high caspase-3 activity levels were found to correlate with a higher growth inhibition in PUFA-treated cells. DHA appears to be a more potent growth inhibitor than EPA and the DHA/EPA combination. An increase in the number of apoptotic cells (early + late), ranging from 12.9 to 44.7%, was observed with increasing DHA doses. CONCLUSION: From our data we conclude that PUFAs induce growth inhibition via targeting survivin expression in LS174T cells, which serve as a model for CCSCs.

Antioxidant effect of aqueous extract of sumac (Rhus coriaria L.) in the alloxan-induced diabetic rats.

In this experimental study, 30 adult male Wistar rats divided into 5 groups (n=6). Experimental rats were treated with one intraperitoneal injection of 120 mg/kgbw Alloxan monohydrate alone or in combination with 28 days of oral administration with aqueous extract of Rhus coriaria (50, 100 and 250 mg/kgbw) while the control rats received normal saline. At the end of the study, blood glucose, malondialdehyde concentration and catalase activities of kidney and liver tissues were determined. Treatment with Rhus coriaria extract resulted in a significant reduction in blood glucose, and the liver and kidney tissue contents of malondialdehyde in comparison to diabetic group (P<0.05). Furthermore, diabetic group treated with extract showed a significant increase in catalase activities of the liver and kidney (P<0.05). The present study showed that Rhus coriaria could be effective in decreasing diabetic complication and this effect is attributed to the antioxidant activity of the plant.

Hydro-methanolic extract of cornus MAS L. And blood glucose, lipid profile and hematological parameters of male rats.

BACKGROUND: Cornus mas L, an olive-shaped red-colored single-seeded fruit, is used in traditional medicine in different parts of Europe and Asia. OBJECTIVES: In the present study, 40 male Wistar rats were randomly divided into five groups, and the effects of 21 days of intraperitoneally (IP) administration of 50, 200 and 400 mg/kg body weight of C. mas hydro-methanolic extract on the rats hematological and biochemical parameters were investigated. The experimental study was carried out in Tabriz, Iran. MATERIALS AND METHODS: The hematology and biochemical tests were performed by the Technicon H1 Hematology Analyzer and enzymatic methods, respectively. RESULTS: The results indicated that all doses of the extract caused significant (P < 0.05) decreases in the hemoglobin distribution width (HDW) (2.3 ± 0.2 vs. 2.5 ± 0.2, P = 0.049) and platelet distribution width (PDW) (56.5 ± 1.8 vs. 63.9 ± 3.6, P = 0.001) of the treated groups vs. control group, whereas only high doses caused significant elevation in the mean corpuscular hemoglobin concentration (MCHC) (30.3 ± 0.8 vs. 28.6 ± 0.6, P = 0.047), mean platelet volume (MPV) (5.0 ± 0.6 vs. 4.1 ± 0.3, P = 0.002), total platelet mass (PCT) (0.33 ± 0.07 vs. 0.26 ± 0.01, P = 0.050), and significant decrease in the red cell distribution width (RDW) (13.8 ± 0.4 vs. 14.7 ± 1.3, P = 0.048) of the treated groups vs. control group. CONCLUSIONS: Decreasing effect of the extract on platelet activity might classify it as an alternative for antiplatelet therapy in cardiovascular diseases (CVD). The results of this study suggested that further investigations with higher doses of C. mas fruit extract are necessary to obtain significant protective and nonprotective changes in hematological and biochemical parameters.

Antihyperglycemic and Antihyperlipidemic Effects of Fruit Aqueous Extract of Berberis integerrima Bge. in Streptozotocin-induced Diabetic Rats.

Use of medicinal plants for attenuation of hyperglycemia and restoration of lipids disorder to normal level is clinically very important. The aim of present study was to evaluate the effects of Berberis integerrima Bge. fruit aqueous extract (BIFAE) on blood glucose and lipid profile in streptozotocin (STZ) - induced diabetic rats. The STZ-induced diabetic rats were treated by fruit aqueous extract of Berberis integerrima Bge. at doses (250 and 500 mg/Kg bw) and glibenclamide (0.6 mg/Kg bw) for 42 days by gavage. Blood glucose levels and body weights of rats were measured on weeks 0, 2, 4 and 6. Total lipid levels were determined in normal and STZ-induced diabetic rats after administration of the BIFAE and glibenclamide for 42 days. STZ-induced diabetic rats showed a significant (P<0.001) increases in the levels of blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C) while body weight and high density lipoprotein HDL-cholesterolan (HDL-C) were significantly(P<0.001) decreased compared to normal rats. Daily administration of BIFAE did not possess the hypoglycemic and hypolipidaemic activity in STZ- diabetic rats during 6-week treatment period. Results indicate the usage of BIFAE in traditional medicine for the treatment of diabetes may need more investigation.

The effect of Equisetum arvense L. (Equisetaceae) in histological changes of pancreatic beta-cells in streptozotocin-induced diabetic in rats.

In view of alleged, the methanolic extract of Equisetum arvense was analysed for its antidiabetic activity in streptozotocin-induced diabetic rats. The blood glucose lowering activity of the methanolic extract was determined in streptozotocin-induced (50 mg kg(-1), i.p.; dissolved in normal saline) diabetic rats, after oral administration in doses of 50 and 250 mg kg(-1) daily for 5 weeks. The data was compare statistically using one-way ANOVA tukey test. The results showed methanolic extract of Equisetum arvense produced a significant antidiabetic activity at doses 50 and 50 mg kg(-1)/b.wt. Concurrent histological studies of the pancreas of these animals showed comparable regeneration by methanolic extract which were earlier, necrosed by streptozotocin.