Fabrication and evaluation of anticancer potential of diosgenin incorporated chitosan-silver nanoparticles; in vitro, in silico and in vivo studies.

The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 µg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer.

Identification of potential agonist-like molecules for α2-adrenergic receptor by multi-layer virtual screening to combat sinusitis.

Sinusitis is one of the most common respiratory inflammatory conditions and a significant health issue that affects millions of people worldwide with a global prevalence of 10-15%. The side effects of available drug regimens of sinus infection demand the urgent development of new drug candidates to combat sinusitis. With the aim of identifying new drug-like candidates to control sinus, we have conducted multifold comprehensive screening of drug-like molecules targeting α2-adrenergic receptor (α2-AR), which serve as the primary drug target in sinusitis. By structure-based virtual screening of in-house compound's database, ten molecules (CP1-CP10) with agonistic effects for α2-AR were selected, and their binding mechanism with critical residues of α2-AR and their physicochemical properties were studied. Moreover, the process of receptor activation by these compounds and the conformational changes in α2-AR caused by these molecules, were further explored by molecular dynamic simulation. The MM-PBSA estimated free energies of compounds are higher than that of reference agonist (ΔGTOTAL = -39.0 kcal/mol). Among all, CP2-CP3, CP7-CP8 and CP6 have the highest binding free energies of -78.9 kcal/mol, -77.3 kcal/mol, -75.60 kcal/mol, -64.8 kcal/mol, and -61.6 kcal/mol, respectively. While CP4 (-55.0 kcal/mol), CP5 (-49.2 kcal/mol), CP9 (-54.8 ± 0.07 kcal/mol), CP10 (-56.7 ± 0.10 kcal/mol) and CP1 (-46.0 ± 0.08 kcal/mol) also exhibited significant binding free energies. These energetically favorable binding energies indicate strong binding affinity of our compounds for α2-AR as compared to known partial agonist. Therefore, these molecules can serve as excellent drug-like candidates for sinusitis.

Effect of dietary inclusion of mealworm frass on growth, hematology, and serum biochemistry of sheep.

Frass is the main component of worm by-product which exhibit anti-microbial and anti-pathogenic properties. In the present study, we assessed the possibility of mealworm frass in sheep feeding regime and evaluated its effect on health and growth performance of sheep. A total of 09 experimental sheep (18-24 months of age) were grouped into three categories (T1, T3, and T3); each group comprised 3 animals including 2 males and 1 female. Group T1 was considered control, group T2 contains 75% commercial feed and 25 mealworm frass, and T3 was 50:50 of commercial feed and mealworm frass. The sheep in group T2 showed average weight gain of 2.9 kg; however, when the dietary inclusion increased up to 50% of mealworm frass or decreased up to 50% of concentrate feed, the average weight gain decreased up to 2.01 kg (group T3). Moreover, the sheep fed with 25% mealworm frass exhibited the lowest feed refusal percentage (6.33%) in total duration of the dietary period (6 weeks). The highest volume of RBC was found in blood collected from sheep fed within group T2 (10.22 1012/L ± 0.34), followed by sheep fed in group T3 (8.96 × 1012/L ± 0.99) (P < 0.05). Significantly (P < 0.05) highest MCV volume in fL (femtoliter) was found in group T2 (32.83 ± 0.44) followed by group T3 (31.23 ± 0.23). The animals in group T3 showed significantly (P < 0.05) highest MCHC volume (40.47 g/dL ± 0.62) followed by group T2 (38.77 ± 0.97). Similar trend was found in MPV (fL); significantly (P < 0.05) highest MPV volume was found in group T3 (12.63 ± 0.09) followed by group T2 (12.53 ± 0.33). Significantly (P < 0.05) high serum phosphorous (P) (6.00 ± 0.29), TG (60.03 ± 3.11), and TP (7.63 g/dL ± 0.23) levels were found in group T3, followed by animals in group T2. We can conclude that inclusion of mealworm frass to replace 25% commercial concentrate feed improved the growth rate and overall health status of the sheep. The present study laid a foundation for the utilization of the mealworm frass (waste product) in ruminant feeding.

Genetic variants of TORC1 gene promoter and their association with carcass quality and body measurement traits in Qinchuan beef cattle.

In the present study, sequencing of TORC1 prompter region explored three SNPs at loci g.80G>T, g.93A>T, and g.1253G>A. The SNP1 produced GG, GT and TT, SNP2 AA, AT and TT, and SNP3 produced GG, GA and AA genotypes. Allelic and genotypic frequencies analysis exhibited that SNP1 is within Hardy-Weinberg equilibrium (HWE). All three SNPs were found highly polymorphic as PIC value (0.25 < PIC < 0.50). At loci g.80G>T the cattle with genotype GG showed significantly (P <0.01) larger body length (BL), Wither height (WH), Hip height (HH), Rump length (RL), Hip width (HW), Chest depth (CD), and Chest circumference (CC). The genotype AA at g.93A>T showed significantly (P< 0.01 and 0.05) Larger body length (BL), Wither height (WH), Hip height, Rump length (RL), Hip width (HW), Chest depth (CD), and Chest circumference (CC). Interestingly, the carcass quality parameters such as Ultrasound loin area (ULA) and Intramuscular fat percentage (IF%) was highest in genotype GG at loci g.1253G>A. These findings conclude that genotype GG at loci g.80 G>T and AA at loci g.93A>T could be used as genetic markers for body measurement and genotype GG at loci g.1253G>A for carcass quality traits of TORC1 gene in Qinchuan beef cattle.

Antifungal and immunomodulatory potentials of propolis nanoparticles against Fusarium solani in Swiss Albino mice.

The nanotechnology has an important role in improving the efficacy and safety in therapy. The present study explains the antifungal and the immunomodulatory potency of propolis nanoparticles (PNPs) against Fusarium solani in Albino Mice. Disc diffusion method was used for antifungal efficacy of PNPs. Moreover, PNPs exhibited a progressive decrease in the % of viable Vero cells and suppressed the virulence factors of Fusarium saloni including adhesion and biofilm formation. In animal experiments, lymphoid cell, peritoneal phagocytes, red blood cell RBCs and white blood cell WBCs counts and the activities of T and B-lymphocytes were determined. In addition, T-cell mitogenesis cells, serum level of interleukin 2 (IL-2) and haemoglobin Hb concentration were measured. PNPs exhibited high inhibition zone with most of Fusarium solani isolates. The results indicated that treatment of mice by PNPs showed a marked rise in the number of cells from thymus, spleen, mesenteric lymph nodes and bone marrow. Furthermore, PNPs caused statistically significant raised in Hb concentration and WBCs count. These results confirmed that many biological activities attributed to PNPs and is as an adjuvant for immune enhancement.

Antifungal potency of Nigella sativa seeds extract against Rhizopus stolonifer and their effect of immunomodulatory against aflatoxin-fed mice.

The present study describes the antifungal potency of Nigella sativa seeds extract and the effect of immunomodulatory of N. sativa against aflatoxin- fed mice. Disc diffusion method was used for antifungal efficacy of aqueous extract of N. sativa. In animal experiments, lymphoid cell count, total and differential counts of PEC, the phagocytic activity of PEC and detection of the plaque-forming were determined. E-rosette-forming cells (RFC), T-cell mitogenesis assay cells, ALT and AST were detected. The aqueous extract of N. sativa (50%) exhibited high inhibition zone with most of isolates of R. stolonifera.The results indicated that treatment of mice by using N. sativa showed marked rise in the number of cells from thymus and PLN with dose 0.50 g and absolute number and comparative ratio of macrophages (P < 0.01) with the doses 0.40 and 0.50 g. There is gradually rise in the scavenger activity of PEC with the dose 0.50 g at 60 min. Serum level of ALT was markedly reduced with dose 0.50 g as compared with a control group. These results indicated that N. sativa is promising modifier of biological response.