β-Cell Autophagy Pathway and Endoplasmic Reticulum Stress Regulating-Role of Liposomal Curcumin in Experimental Diabetes Mellitus: A Molecular and Morphometric Study

Background: Autophagy can confer protection to pancreatic β-cells from the harmful effects of metabolic stress by delaying apoptosis. Curcumin (CUR) alleviates oxidative and endoplasmic reticulum (ER) stress, activates autophagy, reduces inflammation, and decreases β-cell damage in type I diabetes. Liposomal CUR (LPs-CUR) has a higher therapeutic value and better pharmacokinetics than CUR. Objectives: We determined LPs-CUR’s ability to alleviate stress, reduce β-cell damage and unraveled the mechanism underlying its protective effect using a streptozotocin (STZ)-induced type I diabetic rat model. Methods: Sprague–Dawley rats were grouped into vehicle control, STZ-diabetic (STZ 65 mg/kg), STZ-diabetic-3-MA (3-methyladenine [3-MA] 10 mg/kg b.wt), STZ. diabetic-LPs-CUR (LPs-CUR 10 mg/kg b.wt), and STZ diabetic-LPs-CUR-3-MA (LPs-CUR 10 mg/kg b.wt; 3-MA 10 mg/kg b.wt). Results: LPs-CUR significantly reduced blood glucose, oxidative stress, and cellular inflammation in the pancreatic tissue (p < 0.001). ER stress-dependent genes included ATF-6, eIF-2, CHOP, JNK, BiP, and XBP LPs-CUR significantly suppressed fold changes, while it upregulated the autophagic markers Beclin-1 and LC3-II. Conclusions: LP-CUR ameliorates β-cell damage by targeting the autophagy pathway with the regulatory miRNAs miR-137 and miR-29b, which functionally abrogates ER stress in β-cells. This study presents a new therapeutic target for managing type I diabetes using miR-137 and miR-29b

Changing dietary n-6:n-3 ratio using different oil sources affects performance, behavior, cytokines mRNA expression and meat fatty acid profile of broiler chickens

Typical formulated broiler diets are deficient in n-3 poly-unsaturated fatty acids (PUFA) due to widening n-6:n-3 PUFA ratio which could greatly affect performance, immune system of birds and, more importantly, meat quality. This study was conducted to evaluate the effect of modifying dietary n-6:n-3 PUFA ratio from plant and animal oil sources on performance, behavior, cytokine mRNA expression, antioxidative status and meat fatty acid profile of broiler chickens. Birds (n = 420) were fed 7 diets enriched with different dietary oil sources and ratios as follows: sunflower oil in control diet (C); fish oil (FO); 1:1 ratio of sunflower oil to FO (C1FO1); 3:1 ratio of sunflower oil to fish oil (C3FO1); linseed oil (LO); 1:1 ratio of sunflower oil to linseed oil (C1LO1); 3:1 ratio of sunflower oil to linseed oil (C3LO1), resulting in dietary n-6:n-3 ratios of approximately 40:1, 1.5:1, 4:1, 8:1, 1:1, 2.5:1 and 5:1, respectively. The best final body weight, feed conversion ratio as well as protein efficiency ratio of broilers were recorded in the C1FO1 and C1LO1 groups. Compared with the control group, the dressing percentage and breast and thigh yield were highest in the C1FO1 and C1LO1 groups. Narrowing the dietary n-6:n-3 ratio increased (P < 0.05) n-3 PUFA content of breast meat. Moreover, the breast meat contents of eicosapentaenoic acid and docosahexaenoic acid increased (P < 0.05) with increasing dietary FO whereas α-linolenic acid content was higher with LO supplementation. Also, enriching the diets with n-3 PUFA from FO and LO clearly decreased (P < 0.05) serum total cholesterol, triglycerides and very low-density lipoproteins and enhanced antioxidative status. The feeding frequency was decreased (P < 0.05) in the C1FO1 and C1LO1 groups. Likewise, n-3 PUFA-enriched diets enhanced the frequency of preening, wing flapping and flightiness. Animal oil source addition, compared to plant oil, to broiler diets enhanced the relative mRNA expression of interferon gamma, interleukin-1 beta, interleukin-2 and interleukin-6 genes, especially at low n-6:n-3 ratios. This study has clearly shown that narrowing n-6:n-3 ratio through the addition of FO or LO improved performance and immune response of broilers and resulted in healthy chicken meat, enriched with long chain n-3 PUFA. Keywords: Broiler, n-6:n-3 PUFA ratio, Performance, Antioxidant status, Meat, Immunit

Effect of Dietary Modulation of Selenium Form and Level on Performance, Tissue Retention, Quality of Frozen Stored Meat and Gene Expression of Antioxidant Status in Ross Broiler Chickens

This study compares between different selenium forms (sodium selenite; SeS, selenomethionine; Met-Se or nano-Se) and levels on growth performance, Se retention, antioxidative potential of fresh and frozen meat, and genes related to oxidative stress in Ross broilers. Birds (n = 450) were randomly divided into nine experimental groups with five replicates in each and were fed diets supplemented with 0.3, 0.45, and 0.6 mg Se/kg as (SeS, Met-Se), or nano-Se. For overall growth performance, dietary inclusion of Met-Se or nano-Se significantly increased (p &lt; 0.05) body weight gain and improved the feed conversion ratio of Ross broiler chicks at the level of 0.45 and 0.6 mg/kg when compared with the group fed the same level of SeS. Se sources and levels significantly affected (p &lt; 0.05) its concentrations in breast muscle, liver, and serum. Moreover, Se retention in muscle was higher (p &lt; 0.05) after feeding of broiler chicks on a diet supplemented with Met-Se or nano-Se compared to the SeS group, especially at 0.6 mg/kg. Additionally, higher dietary levels from Met-Se or nano-Se significantly reduced oxidative changes in breast and thigh meat in the fresh state and after a four-week storage period and increased muscular pH after 24 h of slaughter. Also, broiler&rsquo;s meat in the Met-Se and nano-Se groups showed cooking loss and lower drip compared to the SeS group (p &lt; 0.05). In the liver, the mRNA expression levels of glutathione peroxidase, superoxide dismutase, and catalase were elevated by increasing dietary Se levels from Met-Se and nano-Se groups up to 0.6 mg/kg when compared with SeS. Therefore, dietary supplementation with 0.6 mg/kg Met-Se and nano-Se improved growth performance and were more efficiently retained than with SeS. Both sources of selenium (Met-Se and nano-Se) downregulated the oxidation processes of meat during the first four weeks of frozen storage, especially in thigh meat, compared with an inorganic source. Finally, dietary supplementation of Met-Se and nano-Se produced acceptable Se levels in chicken meat offered for consumers

The Antioxidant Role of a Taurine-Enriched Diet in Combating the Immunotoxic and Inflammatory Effects of Pyrethroids and/or Carbamates in Oreochromis niloticus

Indiscriminate use of insecticides is a major concern due to its ubiquitous occurrence and potential toxicity to aquatic animals. This study investigated the adverse effects of lambda-cyhalothrin (LCT; C23H19ClF3NO3) and methomyl (MTM; C5H10N2O2S) on immune system modulations and growth performance of juvenile fishes. The supportive role of a taurine (TUR; C2H7NO3S)-supplemented diet was also evaluated. Juvenile O. niloticus fishes were exposed to LCT (0.079 µg/L), MTM (20.39 µg/L), or both in water and were fed on a basal diet only or taurine-supplemented basal diet. Exposure to LCT and MTM retarded growth and increased mortality rate. LCT and MTM reduced antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and innate and humoral immunity but upregulated interleukin and chemokine expressions. Moreover, exposure to LCT and MTM elevated 8-OHdG levels and increased the mortality of Oreochromis niloticus after the experimental bacterial challenge. The TUR-enriched diet enhanced antioxidant enzymes and acted as a growth promoter and anti-inflammatory agent. TUR can modify innate and adaptive immune responses. Furthermore, TUR supplementation is a beneficial additive candidate for mitigating LCT and MTM toxicities mixed with O. niloticus aquafeed

Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. Results: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC&alpha;) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. Conclusions: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM

Promising Role of Growth Hormone-Boosting Peptide in Regulating the Expression of Muscle-Specific Genes and Related MicroRNAs in Broiler Chickens

Appropriate skeletal muscle development in poultry is positively related to increasing its meat production. Synthetic peptides with growth hormone-boosting properties can intensify the effects of endogenous growth hormones. However, their effects on the mRNA and miRNA expression profiles that control muscle development post-hatching in broiler chicks is unclear. Thus, we evaluated the possible effects of synthetic growth hormone-boosting peptide (GHBP) inclusion on a chicken’s growth rate, skeletal muscle development-related genes and myomiRs, serum biochemical parameters, and myofiber characteristics. A total of 400 one-day-old broiler chicks were divided into four groups supplied with GHBP at the levels of 0, 100, 200 and 300 μg/kg for 7 days post-hatching. The results showed that the highest levels of serum IGF-1 and GH at d 20 and d 38 post-hatching were found in the 200 μg/kg GHBP group. Targeted gene expression analysis in skeletal muscle revealed that the GHBP effect was more prominent at d 20 post-hatching. The maximum muscle development in the 200 μg/kg GHBP group was fostered by the upregulation of IGF-1, mTOR, myoD, and myogenin and the downregulation of myostatin and the Pax-3 and -7 genes compared to the control group. In parallel, muscle-specific myomiR analysis described upregulation of miR-27b and miR-499 and down-regulation of miR-1a, miR-133a, miR-133b, and miR-206 in both the 200 and 300 μg/kg GHBP groups. This was reflected in the weight gain of birds, which was increased by 17.3 and 11.2% in the 200 and 300 μg/kg GHBP groups, respectively, when compared with the control group. Moreover, the maximum improvement in the feed conversion ratio was achieved in the 200 μg/kg GHBP group. The myogenic effects of GHBP were also confirmed via studying myofiber characteristics, wherein the largest myofiber sizes and areas were achieved in the 200 μg/kg GHBP group. Overall, our findings indicated that administration of 200 μg/kg GHBP for broiler chicks could accelerate their muscle development by positively regulating muscle-specific mRNA and myomiR expression and reinforcing myofiber growth

Therapeutic Potential of Quercetin Loaded Nanoparticles: Novel Insights in Alleviating Colitis in an Experimental DSS Induced Colitis Model

Oxidative stress is considered the main etiologic factor involved in inflammatory bowel disease (IBD). Integration of nanocarriers for natural therapeutic agents with antioxidant and anti-inflammatory potential is a novel promising candidate for curing IBD. Herein, the colonic antioxidant and anti-inflammatory effects of different concentrations of quercetin nanoparticles (QT-NPs) were evaluated using a dextran sulfate sodium (DSS)-induced colitis model. Following colitis induction, the efficacy and mechanistic actions of QT-NPs were evaluated by assessing lesion severity, molecular aids controlling oxidative stress and inflammatory response, and histopathological and immunohistochemistry examination of colonic tissues. Administration of QT-NPs, especially at higher concentrations, significantly reduced the disease activity index and values of fecal calprotectin marker compared to the colitic group. Colonic oxidant/antioxidant status (ROS, H2O2, MDA, SOD, CAT, GPX and TAC) was restored after treatment with higher concentrations of QT-NPs. Moreover, QT-NPs at levels of 20 mg/kg and, to a lesser extent, 15 mg/kg reduced Nrf2 and HO-1 gene expression, which was in line with decreasing the expression of iNOS and COX2 in colonic tissues. Higher concentrations of QT-NPs greatly downregulated pro-inflammatory cytokines; upregulated genes encoding occludin, MUC-2 and JAM; and restored the healthy architectures of colonic tissues. Taken together, these data suggest that QT-NPs could be a promising alternative to current IBD treatments

Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring

In the advanced stages of type 2 diabetes mellitus (T2DM), diabetic liver damage is a common complication that can devastate a patient’s quality of life. The present study investigated the ability of liposomal berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM) and the possible pathways by which it does so. Liver tissue microarchitectures and immunohistochemical staining were applied during the study. The rats were divided into a control non-diabetic group and four diabetic groups, which are the T2DM, T2DM-Lip-BBR (10 mg/kg b.wt), T2DM-Vildagliptin (Vild) (10 mg/kg b.wt), and T2DM-BBR-Vild (10 mg/kg b.wt + Vild (5 mg/kg b.wt) groups. The findings demonstrated that Lip-BBR treatment could restore liver tissue microarchitectures, reduce steatosis and liver function, and regulate lipid metabolism. Moreover, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats. Lip-BBR also activated the GLP-1 expression, which stimulated insulin biosynthesis. It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation. Collectively, Lip-BBR ameliorated diabetic liver injury in a T2DM rat model with its promotion activity of AMPK/mTOR-mediated autophagy and limiting ER stress

β-Cell Autophagy Pathway and Endoplasmic Reticulum Stress Regulating-Role of Liposomal Curcumin in Experimental Diabetes Mellitus: A Molecular and Morphometric Study

Background: Autophagy can confer protection to pancreatic β-cells from the harmful effects of metabolic stress by delaying apoptosis. Curcumin (CUR) alleviates oxidative and endoplasmic reticulum (ER) stress, activates autophagy, reduces inflammation, and decreases β-cell damage in type I diabetes. Liposomal CUR (LPs-CUR) has a higher therapeutic value and better pharmacokinetics than CUR. Objectives: We determined LPs-CUR’s ability to alleviate stress, reduce β-cell damage and unraveled the mechanism underlying its protective effect using a streptozotocin (STZ)-induced type I diabetic rat model. Methods: Sprague–Dawley rats were grouped into vehicle control, STZ-diabetic (STZ 65 mg/kg), STZ-diabetic-3-MA (3-methyladenine [3-MA] 10 mg/kg b.wt), STZ. diabetic-LPs-CUR (LPs-CUR 10 mg/kg b.wt), and STZ diabetic-LPs-CUR-3-MA (LPs-CUR 10 mg/kg b.wt; 3-MA 10 mg/kg b.wt). Results: LPs-CUR significantly reduced blood glucose, oxidative stress, and cellular inflammation in the pancreatic tissue (p < 0.001). ER stress-dependent genes included ATF-6, eIF-2, CHOP, JNK, BiP, and XBP LPs-CUR significantly suppressed fold changes, while it upregulated the autophagic markers Beclin-1 and LC3-II. Conclusions: LP-CUR ameliorates β-cell damage by targeting the autophagy pathway with the regulatory miRNAs miR-137 and miR-29b, which functionally abrogates ER stress in β-cells. This study presents a new therapeutic target for managing type I diabetes using miR-137 and miR-29b

Impact of Omega-3 Fatty Acids Nano-Formulation on Growth, Antioxidant Potential, Fillet Quality, Immunity, Autophagy-Related Genes and <i>Aeromonas hydrophila</i> Resistance in Nile Tilapia (<i>Oreochromis niloticus</i>)

In modern aquaculture, enriching Nile tilapia’s diet with omega-3 poly-unsaturated fatty acids (PUFAs) not only plays an important role in its general health but also fortifies its fillet with omega-3-PUFAs. However, the major challenge affecting their delivery is their high instability due to oxidative deterioration. Thus, the prospective incorporation of omega-3-PUFAs into nanocarriers can enhance their stability and bioactivity. In this regard, the effect of reformulated omega-3-NPs was investigated on Nile tilapia’s performance, flesh antioxidant stability, immunity, and disease resistance. Four fish groups supplemented with omega-3-PUFAs-loaded nanoparticles (omega-3 NPs) at levels of 0, 1, 2, and 3 g/kg diet and at the end of feeding trial fish challenged with Aeromonas hydrophila. Fish performance (weight gain and feed conversion) was improved in groups supplemented with omega-3-NPs (2 and 3 g/kg diet). The deposition of omega-3-PUFAs in fish flesh elevated with increasing dietary omega-3-NPs. Simultaneously the oxidative markers (H2O2, MDA, and reactive oxygen species) in fish flesh were reduced, especially with higher omega-3-NPs. Post-challenge, downregulation of IL-1β, IL-6, IL-8, TNF-α, and caspase-1 were noticed after dietary supplementation of omega-3-NPs. Moreover, mRNA expression of autophagy-related genes was upregulated while the mTOR gene was downregulated with higher omega-3 NPs levels. Lower expression of A. hydrophila ahyI and ahyR genes were detected with omega-3 NPs supplementation. In conclusion, omega-3-NPs application can fortify tilapia flesh with omega-3-PUFAs and augment its performance, immunity, and disease resistance against Aeromonas hydrophila