Molecular dynamics and QM/MM-based 3D interaction analyses of cyclin-E inhibitors

Abnormal expression of cyclin-dependent kinase 2 (CDK2)/cyclin-E is detected in colorectal, ovarian, breast and prostate cancers. The study of CDK2 with a bound inhibitor revealed CDK2 as a potential therapeutic target for several proliferative diseases. Several highly selective inhibitors of CDK2 are currently undergoing clinical trials, but possibilities remain for the identification and development of novel and improved inhibitors. For example, in silico targeting of ATP-competitive inhibitors of CDKs is of special interest. A series of 3,5-diaminoindazoles was studied using molecular docking and comparative field analyses. We used post-docking short time molecular dynamics (MD) simulation to account for receptor flexibility. The three types of structures, i.e., the highest energy, lowest energy and the structure most resembling the X-ray structure (three complexes) were identified for all ligands. QM/MM energy calculations were performed using a DFT b3lyp/6–31 g* and MM OPLS-2005 force field. Conceptual DFT properties such as the interaction energy of ligand to protein, global hardness (η), HOMO density, electrostatic potential, and electron density were calculated and related to inhibitory activity. CoMFA and CoMSIA were used to account for steric and electrostatic interactions. The results of this study provide insight into the bioactive conformation, interactions involved, and the effect of different drug fragments over different biological activities.     

Genetic diversity and population structure of Moringa oleifera

Moringa is a genus of the tropical flowering plant family Moringaceae containing 13 diverse species. Among the different species, only Moringa oleifera L. is cultivated. This species has great potential in serving as a high-value crop for food, medicinal products, as well as fodder for animals, particularly in developing tropical regions of the world. In this study, the genetic diversity and population structure of world-wide collections of M. oleifera were investigated using DNA markers. A total of 19 microsatellite or simple sequence repeat (SSR) markers along with a partial sequence of the chloroplast gene atpB were used to study genetic diversity within 161 accessions of M. oleifera collected from Asia, Africa, North and South America, and the Caribbean. On average, 8.3 alleles/per SSR were amplified in each accession. A total number of 158 alleles were detected in 131 accessions collected from the wild in Pakistan and from 30 accessions obtained from ECHO (Florida). Observed heterozygosity varied from 0.16 to 0.86, with an average of 0.58, while the average PIC value was 0.59. Partial sequencing of chloroplast genes of 43 of 161 plants generated mixed patterns. These findings have demonstrated that there is a large genetic diversity present in wild collections of M. oleifera collected in Pakistan; whereas low genetic diversity is detected in cultivated accessions obtained from ECHO. Taken together, these results agree with previous reports that M. oleifera is native to the Indo-Pakistan ecological region, and provides sufficient diversity for genetic exploration as well as for genetic improvement efforts.     

Increasing the Contrast of the Brain MR FLAIR Images Using Fuzzy Membership Functions and Structural Similarity Indices in Order to Segment MS Lesions

Segmentation is an important step for the diagnosis of multiple sclerosis (MS). This paper presents a new approach to the fully automatic segmentation of MS lesions in Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance (MR) images. With the aim of increasing the contrast of the FLAIR MR images with respect to the MS lesions, the proposed method first estimates the fuzzy memberships of brain tissues (i.e., the cerebrospinal fluid (CSF), the normal-appearing brain tissue (NABT), and the lesion). The procedure for determining the fuzzy regions of their member functions is performed by maximizing fuzzy entropy through Genetic Algorithm. Research shows that the intersection points of the obtained membership functions are not accurate enough to segment brain tissues. Then, by extracting the structural similarity (SSIM) indices between the FLAIR MR image and its lesions membership image, a new contrast-enhanced image is created in which MS lesions have high contrast against other tissues. Finally, the new contrast-enhanced image is used to segment MS lesions. To evaluate the result of the proposed method, similarity criteria from all slices from 20 MS patients are calculated and compared with other methods, which include manual segmentation. The volume of segmented lesions is also computed and compared with Gold standard using the Intraclass Correlation Coefficient (ICC) and paired samples t test. Similarity index for the patients with small lesion load, moderate lesion load and large lesion load was 0.7261, 0.7745 and 0.8231, respectively. The average overall similarity index for all patients is 0.7649. The t test result indicates that there is no statistically significant difference between the automatic and manual segmentation. The validated results show that this approach is very promising.     

Comparative Efficacy of Weed Control Practices for Parthenium Weed and Sunflower Crop under Varying Tillage Systems

Parthenium poses serious threat to modern crop production system and necessitate evaluating control practices for its effective management. Efficacy of different weed control practices for controlling parthenium was explored in conventional and deep tillage systems in the field conditions. Hand hoeing (20 and 35 days after emergence), S-Metolachlor (pre-emergence herbicide), sorghum straw mulch @ 5 tons ha^-1 and combination of hand hoeing and sorghum straw mulch (hand hoeing at 20 and straw mulch at 35 days after emergence) were used as weed control practice. Weedy check where no weed control measure was applied was also included in this experiment for comparison. Results concluded that the all weed management treatments significantly reduced parthenium density, its fresh and dry biomass during both the years of study as compared to weedy check. Maximum sunflower achene yield was recorded in hand hoeing (20 and 35 days after emergence) in combination with deep tillage. So, mold bold plough used for the purpose of deep tillage should be encouraged for better control of parthenium and higher achene yield of sunflower crop (3293.3 kg ha^-1 in 2017 and 3221.3 kg ha^-1 in 2018). Moreover, is also inferred that total dose of herbicide might be reduced by using hoeing and mulching in an integrated way.     

Assessment of Heavy Metal Pollution and Human Health Risks Assessment in Soils Around an Industrial Zone in Neyshabur,Iran

Biological Trace Element Research - Heavy metal pollution of soils in industrial zones continues to attract attention because of its potential human health risks. The present research is an attempt...     

Decellularized amniotic membrane Scaffolds improve differentiation of iPSCs to functional hepatocyte-like cells

Human-induced pluripotent stem cells-derived hepatocyte-like cells (hiPSCs-HLCs) holds considerable promise for future clinical personalized therapy of liver disease. However, the low engraftment of these cells in the damaged liver microenvironment is still an obstacle for potential application. In this study, we explored the effectiveness of decellularized amniotic membrane (dAM) matrices for culturing of iPSCs and promoting their differentiation into HLCs. The DNA content assay and histological evaluation indicated that cellular and nuclear residues were efficiently eliminated and the AM extracellular matrix component was maintained during decelluarization. DAM matrices were developed as three-dimensional scaffolds and hiPSCs were seeded into these scaffolds in defined induction media. In dAM scaffolds, hiPSCs-HLCs gradually took a typical shape of hepatocytes (polygonal morphology). HiPSCs-HLCs that were cultured into dAM scaffolds showed a higher level of hepatic markers than those cultured in tissue culture plates (TCPs). Moreover, functional activities in term of albumin and urea synthesis and CYP3A activity were significantly higher in dAM scaffolds than TCPs over the same differentiation period. Thus, based on our results, dAM scaffold might have a considerable potential in liver tissue engineering, because it can improve hepatic differentiation of hiPSCs which exhibited higher level of the hepatic marker and more stable metabolic functions.     

Silicon Nanoparticles Mediated Increase in Glandular Trichomes and Regulation of Photosynthetic and Quality Attributes in Mentha piperita L.

Journal of Plant Growth Regulation - Interest in the use of the nanoparticles as plant growth elicitors mushroomed within the last decade and the field is quite intriguing to meet the growing needs...     

Production of ascorbic acid,total protein,callus and root in vitro of non-heading Chinese cabbage by tissue culture

Molecular Biology Reports - The objective of the present work was the selection of cultivar, suitable medium and explant type for callus, root production, ascorbic acid, total ascorbic acid,...     

Protective effects of Cinnamomum verum,Cinnamomum cassia and cinnamaldehyde against 6-OHDA-induced apoptosis in PC12 cells

Cinnamon (Cinnamomum verum and C. cassia) is a medicinal plant, widely-used as a culinary spice. It possesses various therapeutic effects and can slow down the progression of neurological disorders impressively. In this article, the effects of hydro-alcohol extract and essential oil of C. verum and C. cassia and its main bioactive component cinnamaldehyde, has been examined on 6-OHDA-exposed PC12 cells as an in vitro model of Parkinson's disease. The cytotoxicity and cell apoptosis has been induced by 6-OHDA in PC12 cells. The protective effect was determined by measuring cell viability, the amount of reactive oxygen species (ROS), and apoptosis. Cell viability and apoptosis were assessed using resazurin assay, flow cytometry of propidium iodide (PI) stained cells, and western blot analysis. 6-OHDA resulted in the death and apoptosis of cells while, pretreatment with the extract and essential oil of C. verum and C. cassia at 20 µg/ml and cinnamaldehyde at 5 and 10 µM for 24 h could significantly increase the viability (p?<?0.001), and decrease ROS content (p?<?0.05). Pretreatment with the extracts increased survivin and decreased cyt-c whereas, pretreatment with the essential oil decreased cyt-c, increased survivin, and reduced P-p44/42/p44/42 levels to a level near that of the related control. The extract and essential oil of C. verum and C. cassia can be effective against 6-OHDA cytotoxicity. It is suggested that, the synergistic effects of cinnamaldehyde and other components of extract and essential oil promote cinnamon’s medicinal properties.