The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations.

This study was aimed at probing the modulatory influence of polyflavonoids extracted from Citrus aurantifolia, lemon peel extract (LPE-polyflavonoids), on attenuating diabetes mellitus (DM) and its complications. HPLC investigations of the LPE exhibited the incidence of five flavonoids, including diosmin, biochanin A, hesperidin, quercetin, and hesperetin. The in silico impact on ligand-phosphatidylinositol 3-kinase (PI3K) interaction was investigated in terms of polyflavonoid class to explore the non-covalent intakes and binding affinity to the known protein active site. The drug likeness properties and pharmacokinetic parameters of the LPE-polyflavonoids were investigated to assess their bioavailability in relation to Myricetin as a control. Remarkably, the molecular docking studies demonstrated a prominent affinity score of all these agents together with PI3K, implying the potency of the extract to orchestrate PI3K, which is the predominant signal for lessening the level of blood glucose. To verify these findings, in vivo studies were conducted, utilizing diabetic male albino rats treated with LPE-polyflavonoids and other groups treated with hesperidin and diosmin as single flavonoids. Our findings demonstrated that the LPE-polyflavonoids significantly ameliorated the levels of glucose, insulin, glycogen, liver function, carbohydrate metabolizing enzymes, G6Pd, and AGEs compared to the diabetic rats and those exposed to hesperidin and diosmin. Furthermore, the LPE-polyflavonoids regulated the TBARS, GSH, CAT, TNF-α, IL-1ß, IL-6, and AFP levels in the pancreatic and hepatic tissues, suggesting their antioxidant and anti-inflammatory properties. In addition, the pancreatic and hepatic GLUT4 and GLUT2 were noticeably increased in addition to the pancreatic p-AKT in the rats administered with the LPE-polyflavonoids compared to the other diabetic rats. Remarkably, the administration of LPE-polyflavonoids upregulated the expression of the pancreatic and hepatic PI3K, AMPK, and FOXO1 genes, emphasizing the efficiency of the LPE in orchestrating all the signaling pathways necessitated to reduce the diabetes mellitus. Notably, the histopathological examinations of the pancreatic and hepatic tissues corroborated the biochemical results. Altogether, our findings accentuated the potential therapeutic role of LPE-polyflavonoids in controlling diabetes mellitus.

Therapeutic potential of two formulated novel chitosan derivatives with prominent antimicrobial activities against virulent microorganisms and safe profiles toward fibroblast cells.

The development of new antimicrobial agents has been drawing considerable attention due to the extreme escalation of multi-drug resistant microorganisms. We thus sought to ameliorate the antimicrobial activities of the chitosan (Cs) biopolymer by coupling chitosan with cyclohexanone and 2-N-methyl pyrrolidone, synthesizing two novel Schiff bases (CsSB1 and CsSB2), respectively. FT-IR, TGA, DSC, SEM, and potentiometric titration were employed to characterize the formulated chitosan derivatives. The findings exposed that the degrees of deacetylation were 88.12% and 89.98% for CsSB1 and CsSB2, respectively. The antimicrobial capacities of CsSB1 and CsSB2 were substantially enhanced compared with prime chitosan. Furthermore, the CsSB1 and CsSB2 demonstrated minimum inhibitory concentrations (MIC) of 50 µg/ml in relation to all studied microorganisms, whereas chitosan revealed MIC value of 50 µg/ml only for E. coli. Furthermore, CsSB1 with a concentration of 250 µg/ml manifested the highest antibacterial activity against Gram-positive bacteria. Correspondingly, CsSB2 revealed a comparable trend of microbial hindrance with lower activities. Besides, the two derivatives could thwart the growth of Candida albicans (C. albicans). The cytotoxicity assay of the biomaterials accentuated their biocompatibility with fibroblasts. Collectively, the two formulated chitosan derivatives could competently rival the native chitosan, particularly for future applications in wound healing.

Effect on physiological parameters and semen quality upon oral administration of fresh onion juice to V-line rabbit buck during severe heat stress.

Severe heat stress is recognized as a factor that severely influences the semen quality and antioxidant status of rabbits. In this context, fresh onion juice (FOJ) may be a safe and useful option to improve reproductive performance. This research was designed to evaluate the anti-stress effects of FOJ on physiological and semen parameters in heat-stressed bucks. Thirty-six V-line rabbit bucks were randomly distributed into three groups. The bucks received FOJ orally at different doses [0 (water), 1.5, and 3 ml/kg live body weight] every 2 days over a period of 2 months, with 3 weeks as an adaptation period. FOJ treatments significantly improved semen characteristics, such as libido, mass and individual sperm motility, semen concentration, sperm viability, and acrosome reaction with increased initial seminal fructose, via the oral administration of 1.5 and 3 mL FOJ/kg body weight, compared with the findings in control bucks. Seminal plasma antioxidant status was significantly enhanced by FOJ treatments. It was concluded that the oral administration of FOJ under severe heat stress can improve bucks' semen characteristics and sex hormone concentrations except for testosterone, and it is considered a good strategy for improving the heat resistance of rabbit bucks, possibly due to its antioxidant activity.

Development of Polyvinyl Alcohol/Kaolin Sponges Stimulated by Marjoram as Hemostatic, Antibacterial, and Antioxidant Dressings for Wound Healing Promotion.

The predominant impediments to cutaneous wound regeneration are hemorrhage and bacterial infections that lead to extensive inflammation with lethal impact. We thus developed a series of composite sponges based on polyvinyl alcohol (PVA) inspired by marjoram essential oil and kaolin (PVA/marjoram/kaolin), adopting a freeze-thaw method to treat irregular wounds by thwarting lethal bleeding and microbial infections. Microstructure analyses manifested three-dimensional interconnected porous structures for PVA/marjoram/kaolin. Additionally, upon increasing marjoram and kaolin concentrations, the pore diameters of the sponges significantly increased, recording a maximum of 34 ± 5.8 µm for PVA-M0.5-K0.1. Moreover, the porosity and degradation properties of PVA/marjoram/kaolin sponges were markedly enhanced compared with the PVA sponge with high swelling capacity. Furthermore, the PVA/marjoram/kaolin sponges exerted exceptional antibacterial performance against Escherichia coli and Bacillus cereus, along with remarkable antioxidant properties. Moreover, PVA/marjoram/kaolin sponges demonstrated significant thrombogenicity, developing high thrombus mass and hemocompatibility, in addition to their remarkable safety toward fibroblast cells. Notably, this is the first study to our knowledge investigating the effectiveness of marjoram in a polymeric carrier for prospective functioning as a wound dressing. Collectively, the findings suggest the prospective usage of the PVA-M0.5-K0.1 sponge in wound healing for hemorrhage and bacterial infection control.

Biochemical characterisation and application of keratinase from Bacillus thuringiensis MT1 to enable valorisation of hair wastes through biosynthesis of vitamin B-complex.

This study reports on the exploitation of keratinous hydrolysate by keratinase enzymes to produce vitamin B-complex. Toward this end, keratinase enzyme was produced by Bacillus thuringiensis strain MT1, newly isolated from cattle-yard utilising donkey hairs. Scanning electron microscope (SEM) and Fourier transform infrared spectrophotometer (FTIR) analyses demonstrated hairs disintegration and the disruption of the disulphide bonds of the keratin structure, respectively. The biochemical characterisation of the produced enzyme exhibited optimal activity of 422 U/ml at 50 °C and pH 9 with a molecular mass of 80 kDa. The enzyme activity was entirely deactivated by Ethylenediaminetetraacetic acid (EDTA), implying the existence of a metallokeratinase group. Donkey hairs were thus treated with metallokeratinase, emancipating eight essential and eight more non-essential amino acids, which were identified employing amino acid analyser. These amino acids were subsequently utilised by Saccharomyces cerevisiae strain ATCC 64712, at different concentrations, to produce vitamin B-complex. High-performance liquid chromatography (HPLC) analysis revealed the synthesis of vitamins B1, B2, and B12 at various levels associated with concentrations of supplemented amino acids. This report thus highlights the feasible application of keratinase enzyme as an eco-friendly approach to managing hair waste, and concurrently promotes the implementation of hair-based hydrolysate in vitamin B-complex biosynthesis.

Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats.

The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16h-fasted rats were intraperitoneally injected with STZ at dose of 50mg/kg body weight (b. w.), 15min after the intraperitoneal administration of NA (120mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor ß-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue.

Intralipid supplementation in women with recurrent spontaneous abortion and elevated levels of natural killer cells.

OBJECTIVE: To investigate the efficacy of intralipid supplementation in women with recurrent spontaneous abortion (RSA) and elevated natural killer cell activity undergoing in vitro fertilization/intracytoplasmic sperm injection. METHODS: Between February 10, 2013, and April 30, 2015, a double-blind randomized controlled study was conducted at a center in Egypt. Women with unexplained secondary infertility, RSA, and elevated levels of natural killer cells (>12%) were enrolled and randomly assigned to receive intralipid (2mL diluted at 20% in 250mL saline) or saline (250mL) infusion on the day of oocyte retrieval using random numbers and sealed envelopes. Patients and attending physicians were masked to group assignment. The infusions were repeated within 1week of a positive pregnancy test and then every 2weeks until the end of the first trimester. The primary outcome was chemical pregnancy 14days after embryo transfer. Analyses were by intention-to-treat. RESULTS: Overall, 296 women were enrolled. Chemical pregnancy was recorded for 84 (58.3%) of 144 women in the intralipid group and 76 (50.0%) of 152 in the control group (P=0.129). CONCLUSION: Intralipid supplementation did not increase frequency of chemical pregnancy. However, findings related to ongoing pregnancy and live birth should be investigated further. ClinicalTrials.gov:NCT01788540.

Protective role of omega-3 polyunsaturated fatty acid against lead acetate-induced toxicity in liver and kidney of female rats.

The present study was conducted to investigate the protective role of Omega-3 polyunsaturated fatty acids against lead acetate-induced toxicity in liver and kidney of female rats. Animals were divided into four equal groups; group 1 served as control while groups 2 and 3 were treated orally with Omega-3 fatty acids at doses of 125 and 260 mg/kg body weight, respectively, for 10 days. These groups were also injected with lead acetate (25 mg/kg body weight) during the last 5 days. Group 4 was treated only with lead acetate for 5 days and served as positive control group. Lead acetate increased oxidative stress through an elevation in MDA associated with depletion in antioxidant enzymes activities in the tissues. Moreover, the elevation of serum enzymes activities (ALT, AST, ALP, and LDH) and the levels of urea and creatinine were estimated but total proteins were decreased. Also, lead acetate-treatment induced hyperlipidemia via increasing of lipid profiles associated with decline in HDL-c level. Significant changes of Hb, PCV, RBCs, PLT, and WBCs in group 4 were recorded. The biochemical alterations of lead acetate were confirmed by histopathological changes and DNA damage. The administration of Omega-3 provided significant protection against lead acetate toxicity.