Biosynthesis of zinc oxide nanoparticles via neem extract and their anticancer and antibacterial activities.

In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-Vis), and dynamic light scattering (DLS). Then compare its efficacy as anticancer and antibacterial agents with chemically synthesized ZnO-NPs and the neem leaf extract used for the green synthesis of ZnO-NPs. The TEM, UV-vis, and particle size confirmed that the developed ZnO-NPs are nanoscale. The chemically and greenly synthesized ZnO-NPs showed their optical absorbance at 328 nm and 380 nm, respectively, and were observed as spherical particles with a size of about 85 nm and 62.5 nm, respectively. HPLC and GC-MS were utilized to identify the bioactive components in the neem leaf aqueous extract employed for the eco-friendly production of ZnO-NPs. The HPLC analysis revealed that the aqueous extract of neem leaf contains 19 phenolic component fractions. The GC-MS analysis revealed the existence of 21 bioactive compounds. The antiproliferative effect of green ZnO-NPs was observed at different concentrations (31.25 µg/mL-1000 µg/mL) on Hct 116 and A 549 cancer cells, with an IC50 value of 111 µg/mL for A 549 and 118 µg/mL for Hct 116. On the other hand, the antibacterial activity against gram-positive and gram-negative bacteria was estimated. The antibacterial result showed that the MIC of green synthesized ZnO-NPs against gram-positive and gram-negative bacteria were 5, and 1 µg/mL. Hence, they could be utilized as effective antibacterial and antiproliferative agents.

Multitargeted inhibitory effect of Mitoxantrone 2HCl on cervical cancer cell cycle regulatory proteins: a multitargeted docking-based MM\GBSA and MD simulation study.

Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof therapies. In early-stage cervical cancer may not show any symptoms, however, as the cancer progresses, some people may experience- abnormal vaginal bleeding, watery or bloody vaginal discharge, pain in the pelvis or lower back, pain during sex, and frequent and painful urination. In this study, we screened the complete FDA-approved drug library using a multitargeted inhibitory approach against four cervical cancer proteins, namely mitotic arrest deficient -2, DNA polymerase epsilon B-subunit, benzimidazole-related -1, and threonine-protein kinase-1 which crucially plays its role for the in its development process. We employed the HTVS, SP and XP algorithms for efficient filtering and screening that helped to identify Mitoxantrone 2HCl against all of them with docking and MM\GBSA scores ranging from - 11.63 to - 7.802 kcal/mol and - 74.38 to - 47.73 kcal/mol, respectively. We also evaluated the interaction patterns of each complex and the pharmacokinetics properties that helped gain insight into interactions. Subsequently, we performed multiscale MD simulations for 100 ns to understand the dynamic behaviour and stability of the Mitoxantrone 2HCl -protein complexes that revealed the formation of stable drug-protein complexes and provided insights into the molecular interactions that contribute to Mitoxantrone's inhibitory effects on these proteins and can be a better drug for cervical cancer. However, experimental studies of these findings could pave the way for therapies to combat cervical cancer effectively.

The Influence of a Nanoemulsion of Cardamom Essential Oil on the Growth Performance, Feed Utilization, Carcass Characteristics, and Health Status of Growing Rabbits under a High Ambient Temperature.

Recently, nanotechnology approaches have been employed to enhance the solubility, availability, and efficacy of phytochemicals, overcoming some industrial obstacles and natural biological barriers. In this regard, 120 clinically healthy growing V-line rabbits (5 weeks old) reared during the summer season were divided randomly into four equal experimental groups (30 rabbits each). The first group received a basal diet without the supplementation of the nanoemulsion of cardamom essential oil (NCEO) (0 g/kg diet) and served as a control (NCEO 0). The other groups were given diets containing NCEO at levels of 150 (NCEO 150), 300 (NCEO 300), and 600 (NCEO 600) mg/kg diet, respectively. The growth performance (higher LBW and ADG), feed utilization (lower FCR), dressing percentage, and relative weight of the liver were improved significantly in the NCEO-treated groups compared to the control group. Moreover, the dietary treatment significantly decreased the rectum temperature and respiration rate, minimizing the 350 and 325 mg NECO/kg diets. The erythrocyte count, hematocrit, and hemoglobin concentration were significantly increased (p < 0.05), while white blood cells were significantly diminished (p = 0.0200) in the NCEO300 and NCEO600 groups compared to the control group. Treatment with 300 or 600 mg NCEO/kg significantly increased the blood serum total protein and albumin compared to the control group. Meanwhile, the liver enzymes (AST and ALT), uric acid, and creatinine concentrations decreased significantly in the NCEO300 group compared to the control group. The concentrations of triglycerides and total cholesterol were reduced significantly by the dietary treatment. The total antioxidant capacity, dismutase activity, and glutathione concentration were significantly higher, while the malondialdehyde and protein carbonyl levels were significantly lower in the NCEO300 group than in the control. The inflammatory responses and immunity statuses were improved in the blood serum of the NCEO-treated rabbits compared to the control. Heat-stress-induced pathological perturbations in renal/hepatic tissues and NCEO co-treatment successfully re-established and recovered near-control renal-hepatic morphology. In conclusion, a dietary supplementation of NCEO (300 mg/kg) could effectively enhance growing rabbits' growth indices, feed efficiency, redox balance, immunity, and inflammatory responses during the summer.

Nanostructured Lipid Carriers to Enhance the Bioavailability and Solubility of Ranolazine: Statistical Optimization and Pharmacological Evaluations.

Chronic stable angina pectoris is the primary indication for ranolazine (RZ), an anti-anginal drug. The drug has an anti-ischemic action that is unaffected by either blood pressure or heart rate. Due to the first-pass effect, the drug has a reduced bioavailability of 35 to 50%. The study emphasized developing a novel transdermal drug delivery system of nanostructured lipid carriers (NLCs) for delivering RZ. Many pharmaceutical companies employ lipid nanoparticles as biocompatible carriers for medicinal, cosmetic, and biochemical uses. These carriers are appropriate for many applications, such as topical, transdermal, parenteral, pulmonary, and oral administration, because of the large variety of lipids and surfactants that are readily available for manufacturing. RZ NLCs were made using high-pressure homogenization. Statistical analysis was utilized to find the best formula by varying the concentrations of Precirol ATO 5 (X1), oleic acid (X2), and Tween 80 (X3). Variables such as entrapment effectiveness (EE) (Y1), particle size (Y2), polydispersity index (PDI) (Y3), and zeta potential (Y4) were tested. A variety of tests were performed on the new formulation to ascertain how well it would be absorbed in the body. These tests included in vivo absorption studies, skin permeability assessments, in vitro drug release assessments, and physicochemical analyses. The particle size of RZ-NLCs was shown to be very small (118.4 ± 5.94 nm), with improved EE (88.39 ± 3.1%) and low ZP and PDI (-41.91 ± 0.38 and 0.118 ± 0.028). SEM and TEM analysis confirmed the structure of the NLCs and showed a smooth, spherical surface. Improved RZ-NLCs were used to create NLC gel, which was then tested for elasticity both physically and rheologically. The formulation's elasticity was investigated. Optimized RZ-NLCs and NLCG were found to have transdermal fluxes of 48.369 g/cm2/h and 38.383 g/cm2/h, respectively. These results showed that the transdermal delivery of RZ distribution through NLC's transdermal gel had more significant potential. According to in vivo experiments, the drug's bioavailability in Wistar rats increased when it was delivered through NLCs. The findings demonstrated that NLCs loaded with RZ successfully transported the RZ to the designated site with no interruptions and that a quadratic connection existed between the independent and dependent variables.

Unveiling the multitargeted potency of Sodium Danshensu against cervical cancer: a multitargeted docking-based, structural fingerprinting and molecular dynamics simulation study.

Cervical Cancer (CC) is one of the most common types of cancer in women worldwide, with a significant number of deaths reported yearly. Despite the various treatment options available, the high mortality rate associated with CC highlights the need to develop new and effective therapeutic agents. In this study, we have screened the complete prepared FDA library against the Mitotic kinesin-like protein 1, Cyclin B1, DNA polymerase, and MCM10-ID using three glide-based molecular docking algorithms: HTVS, SP and XP to produce a robust calculation. All four proteins are crucial proteins that actively participate in CC development, and inhibiting them together can be a game-changer step for multitargeted drug designing. Our multitargeted screening identified Sodium (Na) Danshensu, a natural FDA-approved phenolic compound of caffeic acid derivatives isolated from Salvia miltiorrhiza. The docking score ranges from -5.892 to -13.103 Kcal/mol, and the screening study was evaluated with the pharmacokinetics and interaction fingerprinting to identify the pattern of interactions that revealed that the compound has bound to the best site it can be fitted to where maximum bonds were created to make the complex stable. The molecular dynamics simulations for 100 ns were then extended to validate the stability of the protein-ligand complexes. The results provide insight into the repurposing, and Na-danshensu exhibited strong binding affinity and stable complex formation with the target proteins, indicating its potential as a multitargeted drug against CC.Communicated by Ramaswamy H. Sarma.

Chondroprotective Effects of Grapefruit (Citrus paradisi Macfad.) Juice in a Complete Freund's Adjuvant Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is a common disorder that can affect any joint in the human body. This study aimed to examine the anti-arthritic properties of high and low doses of grapefruit juice (GFJ), as grapefruit appears to contain anti-inflammatory biochemicals. Forty male Sprague-Dawley rats weighing 170-180 g were divided into five groups. These groups comprised the untreated control group and osteoarthritic (Osteo) rats administered intra-articular injections of Freund's complete adjuvant (CFA; 0.5 mL; 1 mg/mL) as follows: OA rats administered low doses of GFJ (Osteo+GFJ (low); 5 mL/kg body weight (BW)); OA rats administered high doses of GFJ (Osteo+GFJ (high); 27 mL/kg BW); and OA rats administered diclofenac sodium (Osteo+Diclo) as a reference drug. Injections of CFA induced OA, as indicated by a significant increase in the serum levels of the inflammatory biomarkers C-reactive protein (CRP), interleukin-1ß (IL-1ß), and (prostaglandin (PGE2), as well as matrix metalloproteinases (MMP-1) and cathepsin K. The synovial levels of glycosaminoglycans (GAGs), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6) also increased, with a concomitant reduction in osteocalcin levels. The administration of either high or low doses of GFJ reduced CRP, IL-1ß, PGE2, MMP-1, cathepsin K, and osteocalcin while increasing the synovial levels of GAGs, TNF-α, and IL-6, slowing cartilage degradation and boosting joint function. The results showed comparable histopathological and biochemical responses. A comparison of the treatments showed that high-dose GFJ had a greater chondroprotective effect than low-dose GFJ.