In Vitro and Molecular Docking Evaluation of Larvicidal Effects of Essential Oils of Five Aromatic Plants on the Fall Armyworm Spodoptera frugiperda JE. Smith (Lepidoptera: Noctuidae) from Ivory Coast

Faced with the serious consequences resulting from the abusive and repeated use of synthetic chemicals, today rethinking crop protection is more than necessary. It is in this context that the essential oils of the Lamiaceae Ocimum gratissimum and Ocimum canum, the Poaceae Cymbopogon citratus and nardus and a Rutaceae Citrus sp. of known chemical compositions were experimented. The evaluation of the larvicidal potential of the essential oils was done by the method of topical application of the test solutions, on the L1−L2 stage larvae from the first generation of S. frugiperda obtained after rearing in an air-conditioned room. Lethal concentrations (LC₁₀, LC₅₀ and LC₉₀) were determined after 48 h. After assessing the larvicidal potential of essential oils, molecular docking was carried out to study protein-ligand interactions and their propensity to bind to insect enzyme sites (AChE). The essential oil of O. gratissimum was the most effective with the lowest lethal concentrations (LC₁₀=0.91 %, LC₅₀=1.91 % and LC₉₀=3.92 %). The least toxic oil to larvae was Citrus sp. (LC₁₀=5.44 %, LC₅₀=20.50 % and LC₉₀=77.41 %). Molecular docking revealed that p-cymene and thymol from O. gratissimum essential oil are structurally similar and bind to the AChE active site via predominantly hydrophobic interactions and a H-bond with Tyr374 in the case of thymol. The essential oil of O. gratissimum constitutes a potential candidate for the development of biological insecticides for the fight against insect pests and for the protection of the environment.     

Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.     

Exploring the Therapeutic Properties of Alga-Based Silver Nanoparticles: Anticancer,Antibacterial, and Free Radical Scavenging Capabilities

The current study was designed to evaluate the antioxidant, anticancer and antimicrobial activities of silver nanoparticles (AgNPs) biosynthesized by Spirulina platensis extract. The biosynthesized silver nanoparticles were characterized using Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. The antioxidant activity of the biosynthesized AgNPs were determined via DPPH radical scavenging assay while its anticancer activity was determined using the MTT assay. The antimicrobial activity of the biosynthesized AgNPs were analyzed by disc diffusion method. Spirulina platensis acts as a reducing and capping agent. The efficacy of silver nanoparticles (AgNPs) in inhibiting the growth of Gram-negative bacteria, specifically Acetobacter, Klebsiella, Proteus vulgaris, and Pseudomonas aeruginosa, was assessed by the utilisation of the diffusion method. The study aimed to evaluate the efficacy of biosynthesized silver nanoparticles (AgNPs) against many strains of Pseudomonas aeruginosa bacteria. The findings of the study revealed that when administered in doses of 50 μl, 75 μl, and 100 μl, the largest observed zone of inhibition corresponded to measurements of 10.5 mm, 14 mm, and 16 mm, respectively. A zone of inhibition with dimensions of 8 mm, 10.5 mm, and 12 mm was detected during testing against Acetobacter at concentrations of 50 μl, 75 μl, and 100 μl, respectively. The findings also indicate that there is a positive correlation between the concentration of AgNP and the DPPH scavenging ability of silver nanoparticles. The percentage of inhibition observed at concentrations of 500 μg/ml, 400 μg/ml, 300 μg/ml, 200 μg/ml, and 100 μg/ml were recorded as 80±1.98, 61±1.98, 52±1.5, 42±1.99, and 36±1.97, respectively. In addition, it was observed that the silver nanoparticles exhibited the greatest antioxidant activity at a concentration of 500 g/ml, with a measured value of 80.89±1.99. The IC-50 values, representing the inhibitory concentration required to achieve 50 % inhibition, were found to be 8.16, 19.15, 30.14, 41.13, and 63.11 at inhibition levels of 36±1.97, 42±1.99, 52±1.5, 61±1.98, and 80±1.98, respectively.     

Chemical Composition and Pharmacological Evaluation and of Toddalia asiatica (Rutaceae) Extracts and Essential Oil by in Vitro and in Silico Approaches.

Toddalia asiatica (L.) Lam. is extensively used in traditional medicinal systems by various cultures. Despite its frequent use in traditional medicine, there is still a paucity of scientific information on T. asiatica growing on the tropical island of Mauritius. Therefore, the present study was designed to appraise the pharmacological and phytochemical profile of extracts (methanol, ethyl acetate and water) and essential oil obtained from aerial parts of T. asiatica. Biological investigation involved the evaluation of in vitro antioxidant and enzyme inhibitory potentials. The chemical profile of the EO was determined using gas chromatography coupled to mass spectrometry (GC/MS) analysis, while for the extracts, the total phenolic (TPC) and flavonoid content were quantified as well as their individual phenolic compounds by LC/MS/MS. Quinic acid, fumaric acid, chlorogenic acid, quercitrin and isoquercitrin were the main compounds in the extracts. Highest total phenolic (82.5±0.94 mg gallic acid equivalent (GAE/g)) and flavonoid (43.8±0.31 mg rutin equivalent (RE/g)) content were observed for the methanol extract. The GC/MS analysis has shown the presence of 26 compounds with linalool (30.9 %), linalyl acetate (20.9 %) and β-phellandrene (7.9 %) being most abundant components in the EO. The extracts and EO showed notable antioxidant properties, with the methanol extract proved to be superior source of antioxidant compounds. Noteworthy anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BChE) effects were recorded for the tested samples, while only the methanol and ethyl acetate extracts were active against tyrosinase. With respect to antidiabetic effects, the extracts and EO were potent inhibitors of α-glucosidase, while modest activity was recorded against α-amylase. Docking results showed that linalyl acetate has the highest affinity to interact with the active site of BChE with docking score of −6.25 kcal/mol. The findings amassed herein act as a stimulus for further investigations of this plant as a potential source of bioactive compounds which can be exploited as phyto-therapeutics.     

Clinical and pathological significance of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer

We investigated programmed cell death 1 (PD-1) / programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer (HGSOC) and its relationship to tumor infiltrating lymphocytes (TIL) and prognosis. Formalin fixed paraffin embedded (FFPE) samples of 94 HGSOC cases were included in the study. Immunohistochemical analysis (CD3, CD4, CD8, PD-1 and PD-L1) was performed. Samples were analyzed for expression of immune proteins in the peritumoral stromal and intratumoral areas, scored, and expression was correlated with overall survival, stage, and age. PD-L1 staining ratio with a score greater than 0 was found to have lower survival. There were two positive staining patterns, patchy/diffuse and patchy/focal patterns, in 24 (25.5%) cases. Considering the threshold value ≥5%, we demonstrated that the PD-L1 positive cancer cell membrane immunoreactivity rate and patchy/diffuse PD-L1 expression were 9.6% (n = 9). There was statistically significant relationship between high PD-1 scores and PD-L1 cases of ≥ 5%. A statistically significant difference was found between PD-L1 staining and survival in patients with a threshold ≥ 5%. However an appropriate rate for treatment was determined in 9.6% cases. There was a statistically significant correlation between PD-1 positive TIL score and intratumoral CD3, peritumoral stromal CD3, intratumoral CD4 and intratumoral CD8 positive cells. Survival was lower in cases with higher PD-L1 positive stromal TIL score.     

Reverse Relationship Between Blood Boron Level and Body Mass Index in Humans: Does It Matter for Obesity?

The exact role of boron in humans is not known although its supplementation causes several important metabolic and inflammatory changes. The objective of this study is to evaluate the possibility of an association between blood boron level and obesity in normal, overweight, obese, and morbidly obese subjects. A total number of 80 subjects, categorized into four groups based on their body mass index as normal, overweight, obese, and morbidly obese, were enrolled in this study. Age, sex, body mass index, and blood boron levels were recorded for each subject. Although the distribution of female and male subjects and blood boron levels were similar between groups, the mean age of normal subjects was significantly lower than the others (p?=?0.002). There was a significant relationship between age and quantitative values of body mass index for each subject (β?=?0.24; p?=?0.003). In addition, between blood boron levels and quantitative values of body mass index for each subject, a significant reverse relationship was detected (β?=??0.16; p?=?0.043). Although age seemed to be an important variable for blood boron level and body mass index, blood boron levels were shown to be lower in obese subjects in comparison to non-obese subjects.     

Anthraquinone profile,antioxidant and enzyme inhibitory effect of root extracts of eight Asphodeline taxa from Turkey: can Asphodeline roots be considered as a new source of natural compounds?

Plant-based foods have become attractive for scientists and food producers. Beneficial effects related to their consumption as dietary supplements are due to the presence of natural occurring secondary metabolites. In this context, studies on these products are important for natural and safely food ingredients evaluation. The aim of this study was to evaluate root extract of eight Asphodeline species as antioxidants, enzyme inhibitors and phytochemical content. Spectrophotometric antioxidant and enzyme inhibitory assays were performed. Total phenolic and flavonoids contents as well as the chemical free-anthraquinones profiles were determined using routinely procedure (HPLC-PDA). Data show that Asphodeline roots can be considered as a new source of natural compounds and can be used as a valuable dietary supplement. Some differences related to biological activities can be inferred to other phytochemicals that can be considered in the future for their synergic or competitive activities.     

The impact of binding site waters on the activity/selectivity trade-off of Janus kinase 2 (JAK2) inhibitors

Structure based optimization of B39, an indazole-based low micromolar JAK2 virtual screening hit is reported. Analysing the effect of certain modifications on the activity and selectivity of the analogues suggested that these parameters are influenced by water molecules available in the binding site. Simulation of water networks in combination with docking enabled us to identify the key waters and to optimize our primary hit into a low nanomolar JAK2 lead with promising selectivity over JAK1.     

Combinatorial peptide library screening for discovery of diverse α-glucosidase inhibitors using molecular dynamics simulations and binary QSAR models

Human α-glucosidase is an enzyme involved in the catalytic cleavage of the glucoside bond and involved in numerous functionalities of the organism, as well as in the insurgence of diabetes mellitus 2 and obesity. Thus, developing chemicals that inhibit this enzyme is a promising approach for the treatment of several pathologies. Small peptides such as di- and tri-peptides may be in natural organism as well as in the GI tract in high concentration, coming from the digestive process of meat, wheat and milk proteins. In this work, we reported the first tentative hierarchical structure-based virtual screening of peptides for human α-glucosidase. The goal of this work is to discover novel and diverse lead compounds that my act as inhibitors of α-glucosidase such as small peptides by performing a computer aided virtual screening and to find novel scaffolds for further development. Thus, in order to select novel candidates with original structure we performed molecular dynamics (MD) simulations among the 12 top-ranked peptides taking as comparison the MD simulations performed on crystallographic inhibitor acarbose. The compounds with the lower RMSD variability during the MD, were reserved for in vitro biological assay. The selected 4 promising structures were prepared on solid phase peptide synthesis and used for the inhibitory assay, among them compound 2 showed good inhibitory activity, which validated our method as an original strategy to discover novel peptide inhibitors. Moreover, pharmacokinetic profile predictions of these 4 peptides were also carried out with binary QSAR models using MetaCore/MetaDrug applications.