Computational Drug Design: A Multitargeted Approach in Bladder Cancer

Cancer is a complex, robust disease with multiple redundant disease pathways which lead to tumor development, growth, and eventually even death. Despite known redundancies, cancer therapeutics continue to be developed against a single protein target. Initial disease regression occurs followed by relapse in a drug resistant disease state. In response, combinational drug clinical trial targeting multiple pathways began, and have failed due to increased toxicity caused by adverse drug interactions. Development of a single drug that differentially targets multiple disease pathways will result in a more potent therapeutic while inducing minimal toxicity. This was done computationally through in-lab software packages, like CANDOCK, designed to build novel therapeutics that selectively target user defined protein targets. Four protein targets (androgen receptor, estrogen receptor, glucocorticoid receptor, and peroxisome proliferator-activated receptor gamma) were chosen for their known involvement in bladder cancer proliferation and metastasis. Computationally designed compounds were then synthesized and screened for high potency in bladder cancer cell lines using the CellTiter-Blue cell viability assay. Several compounds decreased the cell viability and hindered growth in both mouse and two human bladder cancer cell lines (MB49, T24, and 5637 cell lines, respectively). In addition, some potent compounds displayed decreased nitrous oxide production in RAW 264.7 cells, a mouse macrophage model, using a Griess assay. Thus showing that these compounds could decrease immunosuppression in the tumor microenvironment and slow cancer cell proliferation in vivo

Calotes emma Gray, 1845 (Squamata: Agamidae): range extension and new addition to the reptilian fauna of Tripura, northeast India

Two new records of Calotes emma Gray, 1845, are reported from Srirampur and Homnpui in the state of Tripura, northeast India. These records are the first from Tripura. Present locality records extended the known distribution of C. emma in Southeast Asia. 

Variation in butterfly diversity and unique species richness along different habitats in Trishna Wildlife Sanctuary, Tripura, northeast India

Quantification of butterfly diversity and species richness is of prime importance for evaluating the status of protected areas. Permanent line transect counts were used to record species richness and abundance of butterfly communities of different habitat types in Trishna wildlife sanctuary. A total of 1005 individuals representing 59 species in 48 genera belonging to five families were recorded in the present study. Of these, 23 species belonged to the family Nymphalidae and accounted for 38.98% of the total species and 45.20% of the total number of individuals. Mature secondary mixed moist deciduous forest showed the maximum diversity and species richness, while exotic grassland showed minimum diversity and species richness. Out of 59 species, 31 are new records for Tripura state, while 21 are unique species and nine are listed in the threatened category. This study revealed that mature secondary forests are more important for butterfly communities, while exotic grasslands have a negative impact on species composition

Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations

Resistance to chemotherapy, enhanced proliferation, invasion, angiogenesis, and metastasis (RPIAM) represent major obstacles that limit the efficacy of cancer treatment especially in advanced stages of cancer. Overcoming or suppressing RPIAM can dramatically improve the treatment outcome. Non-small cell lung cancer (NSCLC) is frequently diagnosed in an advanced stage and often possesses intrinsic resistance to chemotherapy accompanied by the fast development of acquired resistance during the treatment. Oncogenic receptor tyrosine kinases (TKs), specifically epidermal growth factor (EGF) TKs, play an important role in the activation of MAPK/PI3K/Akt/STAT pathways, finally leading to the development of RPIAM. However, the suppression of EGF-TK by different drugs is limited by various defensive mechanisms and mutations. In order to effectively prevent the development of RPIAM in NSCLC, we formulated and tested a multicomponent and multifunctional cancer targeted delivery system containing Nanostructured Lipid Carriers (NLCs) as vehicles, luteinizing hormone release hormone (LHRH) as a cancer targeting moiety, EFG-TK inhibitor gefitinib and/or paclitaxel as anticancer drug(s), siRNA targeted to EGF receptor (EGFR) mRNA as a suppressor of EGF receptors, and an imaging agent (rhodamine) for the visualization of cancer cells. Experimental data obtained show that this complex delivery system possesses significantly enhanced anticancer activity that cannot be achieved by individual components applied separately

Calotes emma Gray, 1845 (Squamata: Agamidae): range extension and new addition to the reptilian fauna of Tripura, northeast India

Two new records of Calotes emma Gray, 1845, are reported from Srirampur and Homnpui in the state of Tripura, northeast India. These records are the first from Tripura. Present locality records extended the known distribution of C. emma in Southeast Asia

Notes on the distribution, habitat, and behavior of Northern Tree Shrew Tupaia belangeri (Mammalia: Scandentia: Tupaiidae) in Tripura, India

A preliminary note on the habitat characteristics and the foraging behavior of Northern Tree Shrew, Tupaia belangeri (Wager, 1841), from Tripura is provided. </p

An easy access to organic salt-based stimuli-responsive and multifunctional supramolecular hydrogels

By exploiting orthogonal hydrogen bonding involving supramolecular synthons and hydrophobic/hydrophilic interactions, a new series of simple organic salt based hydrogelators derived from pyrene butyric acid and its β-alanine amide derivative, and various primary amines has been achieved. The hydrogels were characterised by microscopy, table-top rheology and dynamic rheology. FTIR, variable-temperature 1H NMR and emission spectroscopy established the role of various supramolecular interactions such as hydrogen bonding and π–π stacking in hydrogelation. Single-crystal X-ray diffraction (SXRD) studies supported the conclusion that orthogonal hydrogen bonding involving amide–amide and primary ammonium monocarboxylate (PAM) synthons indeed played a crucial role in hydrogelation. The hydrogels were found to be stimuli-responsive and were capable of sensing ammonia and adsorbing water-soluble dye (methylene blue). All the hydrogelators were biocompatible (MTT assay in RAW 264.7 cells), indicating their suitability for use in drug delivery

A supramolecular topical gel derived from a non-steroidal anti-inflammatory drug, fenoprofen, is capable of treating skin inflammation in mice

A new series of bioconjugates derived from a non-steroidal anti-inflammatory drug (NSAID), namely fenoprofen, has been synthesised by amidation with various biogenic molecules such as β-alanine, aminocaproic acid and tyramine with the aim of converting the NSAID into a supramolecular gelator for plausible biomedical applications. One such bioconjugate (2) showed gelation ability with methylsalicylate (MS) and 1% menthol in methyl salicylate (MMS) solvents. These gels were characterized by table top rheology, high resolution-transmission electron microscopy (HR-TEM) and dynamic rheology. Gelator 2 was found to be biostable both in proteolytic enzymes and in blood serum of BALB/c mouse under physiological conditions. It was also found to be biocompatible, as revealed by the methyl thiazolyldiphenyl tetrazolium bromide (MTT) assay in mouse macrophage RAW 264.7 and mouse myoblast C2C12 cells. The anti-inflammatory response (prostaglandin E2 assay, denoted PGE2 assay) of 2 was comparable to that of the parent drug fenoprofen calcium salt. Finally, a topical gel formulation of 2 displayed in vivo self-delivery application in treating imiquimod (IMQ) induced skin inflammation in BALB/c mice

Dragonflies and damselflies (Insecta: Odonata) of Tripura, northeastern India with a pictorial catalogue.

A survey of Odonata was conducted in four reserve forests, three wildlife sanctuaries and three unclassified natural areas of Tripura, northeastern India from 2008 to 2012, from May to August.  A total of 53 species belonging to 37 genera under nine families of Zygoptera (damselflies) and Anisoptera (dragonflies) were recorded in five years from 1370 points by direct search.  This included 25 species, 16 genera and five families reported as new records for the state.  A list of the species, number of specimens examined, their habitats, local and IUCN status, and worldwide distribution are provided.  A pictorial catalogue of adults of the recorded species is also provided.  </div

Inventory of mammals in protected reserves and natural habitats of Tripura, northeast India with notes on existing threats and new records of Large Footed Mouse-eared Bat and Greater False Vampire Bat

Twenty-four species representing 21 genera, 16 families and 7 orders of mammals were recorded in the Tripura state, northeast India, from an inventory done from 2006 to 2012. Ten of these species were found in wildlife sanctuaries as well as in primary forests. Four species were recorded exclusively from the wildlife sanctuaries and ten species were recorded only from primary forests. Order Primates was the most diverse group represented by 6 species from 4 genera in 3 families. Frequency sightings data showed that 11 species were rare, 2 species were occasional, one species was frequent, and another 10 species were common. Two species, Large-footed Mouse-eared Bat, Myotis sp., and Greater False Vampire Bat, Megaderma lyra, are new records from the study area.  Overall, 23 of the 24 species recorded are listed in the IUCN Red List, 14 species are listed in CITES, and 14 species are protected under the Indian Wildlife Protection Act, 1972. Threats being faced by many of the recorded mammals from human encroachments are highlighted