The corrective role of superparamagnetic iron oxide nanoparticles for the genes controlling hypothalamus-pituitary-testis-axis in male obesity-associated secondary hypogonadism.

Background: Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be an advanced favorable trend in multiple biomedical fields. Aim: In this study, we explore the therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat). Methods: 42 male albino rats split into 7 equal groups: 1-negative control: nonobese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for a period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30 mg/kg); 4-obese given CMC-SPIONs (25 mgFe/kg); 5-obese given CMC-SPIONs (50 mgFe/kg); 6-obese given CMC-SPIONs(25 mgFe/kg) + Orlistat (30 mg/kg), 7-obese given CMC-SPIONs (50 mgFe/kg) + Orlistat (30 mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular, and adipose tissues were collected for biochemical and biomolecular assessments. Results: The HFHF diet for 12 weeks resulted in a significant upsurge in body weight, body mass index, serum fasting glucose, insulin resistance, TAG, total cholesterol, and LDL-c; HDL-c was dropped. Serum FSH, LH, and testosterone values declined. A significant disorder in expression levels of genes regulating the hypothalamic-pituitary-testicular-axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1, and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3, and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25-50 mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility. Conclusion: CMC-SPIONs act as an incoming promising contender for obesity and MOSH disorders management, and need more studies on their mechanisms.

The ameliorative role of Aloe vera-loaded chitosan nanoparticles on Staphylococcus aureus induced acute lung injury: Targeting TLR/NF-κB signaling pathways.

Background: Acute lung injury (ALI) is a severe condition distinguished by inflammation and impaired gas exchange in the lungs. Staphylococcus aureus, a common bacterium, can cause ALI through its virulence factors. Aloe vera is a medicinal plant that has been traditionally used to treat a variety of illnesses due to its anti-inflammatory properties. Chitosan nanoparticles are biocompatible and totally biodegradable materials that have shown potential in drug delivery systems. Aim: To explore the antibacterial activity of Aloe vera-loaded chitosan nanoparticles (AV-CS-NPs) against S. aureus in vitro and in vivo with advanced techniques. Methods: The antibacterial efficacy of AV-CS-NPs was evaluated through a broth microdilution assay. In addition, the impact of AV-CS-NPs on S. aureus-induced ALI in rats was examined by analyzing the expression of genes linked to inflammation, oxidative stress, and apoptosis. Furthermore, rat lung tissue was scanned histologically. The rats were divided into three groups: control, ALI, and treatment with AV-CS-NPs. Results: The AV-CS-NPs that were prepared exhibited clustered semispherical and spherical forms, having an average particle size of approximately 60 nm. These nanoparticles displayed a diverse structure with an uneven distribution of particle sizes. The maximum entrapment efficiency of 95.5% ± 1.25% was achieved. The obtained findings revealed that The minimum inhibitory concentration and minimum bactericidal concentration values were determined to be 5 and 10 ug/ml, respectively, indicating the potent bactericidal effect of the NPs. Also, S. aureus infected rats explored upregulation in the mRNA expression of TLR2 and TLR4 compared to healthy control groups. AV-CS-NP treatment reverses the case where there was repression in mRNA expression of TLR2 and TLR4 compared to S. aureus-treated rats. Conclusion: These NPs can serve as potential candidates for the development of alternative antimicrobial agents.

Effects of Dietary Microbial Muramidase on the Growth, Liver Histoarchitecture, Antioxidant Status, and Immunoexpression of Pro-Inflammatory Cytokines in Broiler Chickens.

The impact of microbial muramidase (MMUR) addition to broiler chicken rations was evaluated through growth parameters, liver histoarchitecture, antioxidant status, biochemical analysis, and expression of pro-inflammatory cytokines for 35 days. Four hundred three-day-old chicks (97.68 ± 0.59 g) were distributed to four distinct groups with ten duplicates each (100 chicks/group) consisting of: group 1 (G1): a basal diet without MMUR (control group); G2: a basal diet + 200 mg MMUR kg-1 G3: a basal diet + 400 mg MMUR kg-1; and G4: a basal diet + 600 mg MMUR kg-1. The results showed that the final body weight and total weight gain were increased (p = 0.015) in birds fed with diets supplemented with MMUR at 600 mg kg-1. The feed conversion ratio (FCR) was improved in all treatment groups compared with the control group. Birds fed with a diet supplemented with 600 mg MMUR kg-1 showed the highest body weight gain and improved FCR. The values of thyroxin hormones and growth hormones were increased in all MMUR-supplemented groups. Dietary MMUR increased the activities of antioxidant enzymes (total antioxidant activity, catalase, and superoxide dismutase) and decreased the activity of malondialdehyde (p < 0.05). In addition, it increased the values of interleukin 1 beta and interferon-gamma compared with the control group. Furthermore, dietary MMUR increased the expression of transforming growth factor-beta immunostaining in the liver and spleen tissues. Our results show that supplementing broilers' diets with 600 mg MMUR kg-1 could enhance the chicken growth rate and improve their antioxidant, inflammatory, and anti-inflammatory responses.

Evaluation of Spray-Dried Bovine Hemoglobin Powder as a Dietary Animal Protein Source in Nile Tilapia, Oreochromis niloticus.

The present study evaluated the potential effects of dietary inclusion of spray-dried bovine hemoglobin powder (SDBH) on the growth, gene expression of peptide and amino acid transporters, insulin growth factor-1 (IGF-1) and myostatin, digestive enzymes activity, intestinal histomorphology and immune status, immune-related gene expression, and economic efficiency in Nile tilapia, Oreochromis niloticus. Two hundred twenty-five fingerlings (32.38 ± 0.05 g/fish) were distributed into five treatments with five dietary inclusion levels of SDBH: 0, 2.5, 5, 7.5, and 10% for a ten-week feeding period. Dietary inclusion of SDBH linearly increased the final body weight (FBW), total weight gain (TWG), specific growth rate (SGR), and protein efficiency ratio (PER). Additionally, a linear decrease in feed conversion ratio (FCR) and daily feed intake relative to the daily BW was reported in the highest inclusion levels (7.5 and 10%). Dietary inclusion of SDBH was associated with a significant increase in the intestinal villous height (VH), villous width (VW), villous height: crypt depth ratio (VH: CD), and muscle coat thickness (MCT), with the highest values reported in SDBH7.5 group. Increased serum growth hormone levels and decreased serum leptin hormone levels were also reported by increasing the SDBH level. The serum glucose level was decreased in the SDBH7.5 and SDBH10 groups. The digestive enzymes' activity (amylase and protease) was increased by increasing the SDBH inclusion level. An up-regulation in the expression of peptide and amino acid transporters, IGF-1, and down-regulation of myostatin was reported in the SDBH2.5 to SDBH7.5 groups. Spleen sections showed more lymphoid elements, especially in the SDBH2.5 and SDBH7.5 groups. The SDBH inclusion increased the serum lysozyme activity, nitric oxide (NO), and complement 3 (C3) levels, with the highest values recorded in the SDBH5 group. The phagocytic % and the phagocytic index were increased by increasing the SDBH inclusion %. The expressions of immune-related genes (transforming growth factor-beta (TGF-ß), Toll-like receptor 2 (TLR2), and interleukin 10 (IL10)) were up-regulated by SDBH inclusion with the highest expression in the SDBH5 group. Economically, the feed costs and feed costs/kg gain were linearly decreased in the SDBH7.5 and SDBH10 diets. In conclusion, spray-dried bovine hemoglobin powder could be used as a protein source for up to 10% of the diets of Nile tilapia for better growth and immune status of fish.

Modulating the Growth, Antioxidant Activity, and Immunoexpression of Proinflammatory Cytokines and Apoptotic Proteins in Broiler Chickens by Adding Dietary Spirulina platensis Phycocyanin.

This study investigated the dietary effect of Spirulina platensis phycocyanin (SPC) on growth performance (body weight (BW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR)) at starter, grower, and finisher stages, intestinal histomorphology, serum biochemical parameters, inflammatory and antioxidant indices, and proinflammatory cytokines (tumor necrosis factor-α and caspase-3) immune expression in broiler chickens. In total, 250 one-day-old chicks (Ross 308 broiler) were randomly allotted to five experimental groups (5 replicates/group, 10 chicks/replicate) and fed basal diets supplemented with five levels of SPC (0, 0.25, 0.5, 0.75, and 1 g kg-1 diet) for 35 days. Compared with SPC0 treatment, different SPC levels increased the overall BW and BWG without affecting the total feed consumption. However, the FCR decreased linearly with an increase in supplementation level. The serum levels of total proteins, albumin, globulins, and growth hormone increased linearly by increasing levels of SPC supplementation. Further, SPC supplementation increased the thyroxin hormones without affecting serum glucose and leptin levels. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) values decreased in broilers fed SPC0.250 and SPC1 diets. Triglycerides (TG) decreased in SPC0.25-, SPC0.75-, and SPC1-treated groups. Though antioxidant enzyme activities (total antioxidant capacity, catalase, and superoxide dismutase) increased linearly and quadratically, malondialdehyde (MDA) decreased linearly by increasing the SPC level. There was no effect on serum proinflammatory cytokines IL1ß levels. Immunolabelling index of caspase-3 and tumor necrosis factor-α (TNF-α) were downregulated by SPC supplementation. The intestinal histomorphology is represented by increased villus height, the villus height to crypt depth ratio, and numbers of goblet cells in different sections of the small intestine. In conclusion, SPC supplementation is beneficial in broiler chicken diets due to its growth-promoting, antioxidant, and anti-inflammatory properties.

Exosomes Derived from BM-MSCs Mitigate the Development of Chronic Kidney Damage Post-Menopause via Interfering with Fibrosis and Apoptosis.

The rate of chronic kidney disease (CKD) is increasing globally, and it is caused by continuous damage to kidney tissue. With time the renal damage becomes irreversible, leading to CKD development. In females, post-menopause lack of estrogen supply has been described as a risk factor for CKD development, and studies targeting post-menopause CKD are scarce. In the present study, we used exosomes isolated from bone marrow mesenchymal stem/stromal cells (BM-MSCs) to test their therapeutic potential against the development of CKD. At first, the menopause model was achieved by surgical bilateral ovariectomy in female albino rats. After that, 100 µg of exosomes was given to ovariectomized rats, and the study continued for 2 months. Changes in urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), kidney antioxidant parameters (SOD, GPx and CAT), histological changes, immunohistochemical levels of caspase 3, and the gene expression of NGAL (related to kidney damage), TGFß1 and αSMA (related to fibrosis and EMT), and caspase 3 (related to apoptosis) were studied. After the ovariectomy, the occurrence of CKD was confirmed in the rats by the drastic reduction of serum estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, reduced GPx SOD, and CAT in kidney tissue, degenerative and fibrotic lesions in the histopathological examination, higher immunohistochemical expression of caspase 3 and increased expression of all studied genes. After exosomes administration, the entire chronic inflammatory picture in the kidney was corrected, and a near-normal kidney structure and function were attained. This study shows for the first time that BM-MSCs exosomes are potent for reducing apoptosis and fibrosis levels and, thus, can reduce the chronic damage of the kidneys in females that are in their menopause period. Therefore, MSCs-derived exosomes should be considered a valuable therapy for preserving postmenopausal kidney structure and function and, subsequently, could improve the quality of females' life during menopause.