Engineered Silybin Nanoparticles Educe Efficient Control in Experimental Diabetes

Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostrate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17±0.01 µg/lit to 0.57±0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.     

Role of cytokines in experimentally induced lung cancer and chemoprevention by COX-2 selective inhibitor, etoricoxib

This study explored the role of pro- and anti-inflammatory cytokines in dimethyl benz(a)anthracene (DMBA)-induced lung cancer and its subsequent correction with a COX-2 inhibitory NSAID, etoricoxib. A single dose of DMBA (20?mg/kg body weight) in 0.9?% NaCl administered intratracheally was used to induce tumors in the rat lungs in 20?weeks. The study of pro-inflammatory cytokines like IL-1??, TNF-??, and IFN-?? revealed their upregulation by DMBA administration and restoration of their levels toward normal by the treatment with etoricoxib, while the anti-inflammatory cytokine IL-2 was found to be down-regulated with carcinogen administration and corrected with etoricoxib treatment. Apoptosis was studied by mitochondrial Bcl-2/Bax ratio and staining with fluorescent dyes acridine orange/ethidium bromide. The results showed a decreased apoptotic level with DMBA which was corrected with etoricoxib. Also, mitochondrial membrane potential was studied using JC-1 and rhodamine-123, which are membrane permeant fluorescent dyes, and generate information about cells at lower and higher mitochondrial membrane potential (???_M). The results showed the presence of maximum number of cells with higher ???_M in the DMBA group and their number was considerably lowered in the other three groups.     

EhCoactosin Stabilizes Actin Filaments in the Protist Parasite Entamoeba histolytica

Entamoeba histolytica is a protist parasite that is the causative agent of amoebiasis, and is a highly motile organism. The motility is essential for its survival and pathogenesis, and a dynamic actin cytoskeleton is required for this process. EhCoactosin, an actin-binding protein of the ADF/cofilin family, participates in actin dynamics, and here we report our studies of this protein using both structural and functional approaches. The X-ray crystal structure of EhCoactosin resembles that of human coactosin-like protein, with major differences in the distribution of surface charges and the orientation of terminal regions. According to in vitro binding assays, full-length EhCoactosin binds both F- and G-actin. Instead of acting to depolymerize or severe F-actin, EhCoactosin directly stabilizes the polymer. When EhCoactosin was visualized in E. histolytica cells using either confocal imaging or total internal reflectance microscopy, it was found to colocalize with F-actin at phagocytic cups. Over-expression of this protein stabilized F-actin and inhibited the phagocytic process. EhCoactosin appears to be an unusual type of coactosin involved in E. histolytica actin dynamics.     

Predicting the Distribution Pattern of Small Carnivores in Response to Environmental Factors in the Western Ghats

Due to their secretive habits, predicting the pattern of spatial distribution of small carnivores has been typically challenging, yet for conservation management it is essential to understand the association between this group of animals and environmental factors. We applied maximum entropy modeling (MaxEnt) to build distribution models and identify environmental predictors including bioclimatic variables, forest and land cover type, topography, vegetation index and anthropogenic variables for six small carnivore species in Mudumalai Tiger Reserve. Species occurrence records were collated from camera-traps and vehicle transects during the years 2010 and 2011. We used the average training gain from forty model runs for each species to select the best set of predictors. The area under the curve (AUC) of the receiver operating characteristic plot (ROC) ranged from 0.81 to 0.93 for the training data and 0.72 to 0.87 for the test data. In habitat models for F. chaus, P. hermaphroditus, and H. smithii “distance to village” and precipitation of the warmest quarter emerged as some of the most important variables. “Distance to village” and aspect were important for V. indica while “distance to village” and precipitation of the coldest quarter were significant for H. vitticollis. “Distance to village”, precipitation of the warmest quarter and land cover were influential variables in the distribution of H. edwardsii. The map of predicted probabilities of occurrence showed potentially suitable habitats accounting for 46 km² of the reserve for F. chaus, 62 km² for V. indica, 30 km² for P. hermaphroditus, 63 km² for H. vitticollis, 45 km² for H. smithii and 28 km² for H. edwardsii. Habitat heterogeneity driven by the east-west climatic gradient was correlated with the spatial distribution of small carnivores. This study exemplifies the usefulness of modeling small carnivore distribution to prioritize and direct conservation planning for habitat specialists in southern India.     

Amelioration of Cancer Stem Cells in Macrophage Colony Stimulating Factor-Expressing U87MG-Human Glioblastoma upon 5-Fluorouracil Therapy

Macrophage colony stimulating factor (MCSF) regulates growth, proliferation and differentiation of haematopoietic cell lineages. Many cancers are known to secrete high level of MCSF, which recruit macrophages into the tumour micro-environment, supporting tumour growth. Herein, we report the cloning of MCSF and subsequent generation of U87MG expressing MCSF stable cell line (U87-MCSF). Cytotoxicity of anti-cancer drug 5-fluorouracil (5-FU) was evaluated on both U87MG and U87-MCSF cells. Interestingly, the proliferation of U87-MCSF cells was less (p<0.001) than that of U87MG cells alone, after treatment with 5-FU. Significant decrease in expression levels of cyclin E and A2 quantified by real time PCR analysis corroborated the reduced proliferation of 5-FU treated U87-MCSF cells. However, JC-1 staining did not reveal any apoptosis upon 5-FU treatment. Notch-1 upregulation induced a possible epithelial-mesenchymal transition in U87-MCSF cells, which accounted for an increase in the proportion of CD24^high/CD44^less cancer stem cells in U87-MCSF cells after 5-FU treatment. The elevated resistance of U87-MCSF cells towards 5-FU was due to the increase in the expressions (10.2 and 6 fold) of ABCB1 and mdm2, respectively. Furthermore, increase in expressions of ABCG1, mdm2 and CD24 was also observed in U87MG cells after prolonged incubation with 5-FU. Our studies provided mechanistic insights into drug resistance of U87MG cells and also described the pivotal role played by MCSF in augmenting the resistance of U87MG cells to 5-FU.     

Impact of chromate and dichromate on lysozyme stability: A spectroscopic and molecular docking investigation

A comparative study of interaction between chicken egg white lysozyme (Lyz) with two hexavalent chromate ions; chromate and dichromate; which are prevalently known for their toxicity, was investigated using different spectroscopic techniques along with a molecular docking study. Both steady-state and time-resolved studies revealed that the addition of chromate/dichromate is responsible for strong quenching of intrinsic fluorescence in Lyz and the quenching is caused by both static and dynamic quenching mechanisms. Different binding and thermodynamic parameters were also calculated at different temperatures from the intrinsic fluorescence of Lyz. The conformational change in Lyz and thermodynamic parameters obtained during the course of interaction with chromate/dichromate were well-supported by the molecular docking results.     

Unravelling the emerging threats of microplastics to agroecosystems

Reviews in Environmental Science and Bio/Technology - In the past few decades, pollution from microplastics has emerged as an important issue on a global scale. These plastic particles are mainly...     

Redox-state dependent blinking of single photosystem I trimers at around liquid-nitrogen temperature

Efficient light harvesting in a photosynthetic antenna system is disturbed by a ragged and fluctuating energy landscape of the antenna pigments in response to the conformation dynamics of the protein. This situation is especially pronounced in Photosystem I (PSI) containing red shifted chlorophylls (red Chls) with the excitation energy much lower than the primary donor. The present study was conducted to clarify light-harvesting dynamics of PSI isolated from Synechocystis sp. PCC6803 by using single-molecule spectroscopy at liquid?nitrogen temperatures. Fluorescence emission at around 720?nm from the red Chls in single PSI trimers was monitored at 80–100?K. Intermittent variations in the emission intensities, so-called blinking, were frequently observed. Its time scale lay in several tens of seconds. The blinking amplitude depended on the redox state of the phylloquinone (A₁). Electrochromic shifts of Chls induced by the negative charge on A₁ were calculated based on the X-ray crystallographic structure. A Chl molecule, Chl-A839 (numbering according to PDB 5OY0), bound near A₁ was found to have a large electrochromic shift. This Chl has strong exciton coupling with neighboring Chl (A838) whose site energy was predicted to be determined by interaction with an arginine residue (ArgF84) [Adolphs et al., 2010]. A possible scenario of the blinking was proposed. Conformational fluctuations of ArgF84 seesaw the excitation-energy of Chl-A838, which perturbs the branching ratio of excitation-energy between the red Chl and the cationic form of P700 as a quencher. The electrochromic shift of Chl-A839 enhances the effect of the conformation dynamics of ArgF84.     

Accumulation of Trace Metals by Mangrove Plants in Indian Sundarban Wetland: Prospects for Phytoremediation

The work investigates on the potential of ten mangrove species for absorption, accumulation and partitioning of trace metal(loid)s in individual plant tissues (leaves, bark and root/pneumatophore) at two study sites of Indian Sundarban Wetland. The metal(loid) concentration in host sediments and their geochemical characteristics were also considered. Mangrove sediments showed unique potential in many- fold increase for most metal(loid)s than plant tissues due to their inherent physicochemical properties. The ranges of concentration of trace metal(loid)s for As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn in plant tissue were 0.006–0.31, 0.02–2.97, 0.10–4.80, 0.13–6.49, 4.46–48.30, 9.2–938.1, 0.02–0.13, 9.8–1726, 11–5.41, 0.04–7.64, 3.81–52.20 μg g ^?1respectively. The bio- concentration factor (BCF) showed its maximum value (15.5) in Excoecaria agallocha for Cd, suggesting that it can be considered as a high-efficient plant for heavy metal bioaccumulation. Among all metals, Cd and Zn were highly bioaccumulated in E. agallocha (2.97 and 52.2 μg g ^?1 respectively. Our findings suggest that the species may be classified as efficient metal trap for Cd in aerial parts, as indicated by higher metal accumulation in the leaves combined with BCF and translocation factor (TF) values.