Aligned nanofibres made of poly(3-hydroxybutyrate) grafted to hyaluronan for potential healthcare applications

In this work, a hybrid copolymer consisting of poly(3-hydroxybutyrate) grafted to hyaluronic acid (HA) was synthesised and characterised. Once formed, the P(3HB)-g-HA copolymer was soluble in water allowing a green electrospinning process. The diameters of nanofibres can be tailored by simply varying the Mw of polymer. The optimization of the process allowed to produce fibres of average diameter in the range of 100-150 nm and low polydispersity. The hydrophobic modification has not only increased the fibre diameter, but also the obtained layers were homogenous. At the nanoscale, the hybrid copolymer exhibited an unusual hairy topography. Moreover, the hardness and tensile properties of the hybrid were found to be superior compared to fibres made of unmodified HA. Particularly, this reinforcement was achieved at the longitudinal direction. Additionally, this work reports the use in the composition of a water-soluble copolymer containing photo cross-linkable moieties to produce insoluble materials post-electrospinning. The derivatives as well as their nanofibrous mats retain the biocompatibility of the natural polymers used for the fabrication

Application of geo-spatial indices for detection of growth dynamics and forms of expansion in English Bazar Urban Agglomeration, West Bengal

In India, urban sprawl of metropolitan cities and other large cities is a widespread concern for planners and policy makers. Modeling urban sprawl of small and medium size towns is completely bypassed urban research of India. This study attempted to fill-up the gap by addressing the three urban growth types of infilling growth, outlying growth and edge-expansion growth of EBM which is a medium size town of West Bengal. In this study, an integrated approach of remote sensing and GIS along with spatial landscape matrices have employed to identify and distinguish between three urban growth types of EBM which helps planners to better identify, understand and address the sprawl of small and medium size towns of developing countries. Result shows that the proposed methods successfully identifies and visualize different urban growth types of EBM. Infilling growth is the dominant expansion type. Edge-expansion is concentrated at suburban areas. Outlying growth mainly occurs relatively far from the urban core. The analysis shows that initially the urban area expands mainly as edge-expanding growth during the different temporal periods. Next, growth shows gradual increasing of the area under outlying growth from phase 1 (1991-2001) to phase 3 (2011-2016) with area cover of 2.04km2-3.25km2. Growth filled in vacant non-urban area inwards, resulting into a more compact and aggregated urban pattern. The study shows an improved understanding of urban growth, and helps to provide an effective way for urban planning

Metabolic diversity and in vitro pancreatic lipase inhibition activity of some varieties of <i>Mangifera indica</i> L. fruits

<p>Mango fruits from different varieties vary in aroma and taste. In this study, methanol extracts of fruit pulps obtained from seven Indian varieties of <i>Mangifera indica</i> (Amrapali, Fazli, Golapkhas, Gopalbhog, Himsagar, Langra, and Mohanbhog) were profiled using a metabolomics approach. Chemometric methods were used to understand the contribution of metabolites to varietal differences. The extracts were also assayed for pancreatic lipase inhibitory activities in vitro. All the pulp extracts were analyzed by GC-MS and HPLC to detect their metabolites. In sum, 63 metabolites were identified. The varieties were distinctly different chemically in terms of the identified metabolites, as revealed by principal component analysis (PCA) and partial least squares – discriminant analysis (PLS-DA). From the biplot and VIP scores, it was observed that in addition to some organic acids, amino acids, sugars, and phenolic constituents (e.g., benzene-1,2,4-triol, mangiferin, and pyrogallol) contributed to this variation. All the varieties also inhibited pancreatic lipase in a dose-dependent manner. Gallic acid (IC₅₀ value 0.47 nM) and 4-hydroxy benzoic acid (IC₅₀ value 1.15 nM) showed high anti-lipase activity. Three amino acids (L-proline (IC₅₀ value 0.01 µM), L-alanine (IC₅₀ value 0.14 µM) and aspartic acid (IC₅₀ value 0.02 µM)), and the inorganic acid phosphoric acid (0.02 µM) also showed activity against pancreatic lipase.</p

Gold nanorod embedded reduction responsive block copolymer micelle-triggered drug delivery combined with photothermal ablation for targeted cancer therapy

Background: Gold nanorods, by virtue of surface plasmon resonance, convert incident light energy (NIR) into heat energy which induces hyperthermia. We designed unique, multifunctional, gold nanorod embedded block copolymer micelle loaded with GW627368X for targeted drug delivery and photothermal therapy. Methods: Glutathione responsive diblock co-polymer was synthesized by RAFT process forming self-assembled micelle on gold nanorods prepared by seed mediated method and GW627368X was loaded on to the reduction responsive gold nanorod embedded micelle. Photothermal therapy was administered using cwNIR laser (808 nm; 4 W/cm²). Efficacy of nanoformulated GW627368X, photothermal therapy and combination of both were evaluated in vitro and in vivo. Results: In response to photothermal treatment, cells undergo regulated, patterned cell death by necroptosis. Combining GW627368X with photothermal treatment using single nanoparticle enhanced therapeutic outcome. In addition, these nanoparticles are effective X-ray CT contrast agents, thus, can help in monitoring treatment. Conclusion: Reduction responsive nanorod embedded micelle containing folic acid and lipoic acid when treated on cervical cancer cells or tumour bearing mice, aggregate in and around cancer cells. Due to high glutathione concentration, micelles degrade releasing drug which binds surface receptors inducing apoptosis. When incident with 808 nm cwNIR lasers, gold nanorods bring about photothermal effect leading to hyperthermic cell death by necroptosis. Combination of the two modalities enhances therapeutic efficacy by inducing both forms of cell death. General significance: Our proposed treatment strategy achieves photothermal therapy and targeted drug delivery simultaneously. It can prove useful in overcoming general toxicities associated with chemotherapeutics and intrinsic/acquired resistance to chemo and radiotherapy. Graphical abstract: Glutathione responsive diblock copolymer containing folic acid and lipoic acid forms self-assembled micelle around gold nanorods (AuNRs). GW627368X loaded AuNR embedded block copolymer micelles served dual purpose of targeted drug delivery and an effective photothermal agent. On reaching tumour vicinity, GSH triggered disassembly of micelles takes place releasing the drug which then binds EP4 receptors bringing about downstream effects. AuNRs start accumulating in and around the tumour/cancerous cells rendering it susceptible to hyperthermal demise. On irradiation with 808 nm NIR lasers, light energy is efficiently converted into heat energy owing to surface plasmon resonance of AuNRs leading to hyperthermal cell death

Comparative Codon and Amino Acid Composition Analysis of Tritryps-Conspicuous Features of Leishmania Major

Comparative analyses of codon/amino acid usage in Leishmania major, Trypanosoma brucei and Trypanosoma cruzi reveal that gene expressivity and GC-bias play key roles in shaping the gene composition of all three parasites, and protein composition of L. major only. In T. brucei and T. cruzi, the major contributors to the variation in protein composition are hydropathy and/or aromaticity. Principle of Cost Minimization is followed by T. brucei, disregarded by T. cruzi and opposed by L. major. Slowly evolving highly expressed gene-products of L. major bear signatures of relatively AT-rich ancestor, while faster evolution under GC-bias has characterized the lowly expressed genes of the species by higher GC12-conten

Proteome Composition in Plasmodium falciparum: Higher Usage of GC-Rich Nonsynonymous Codons in Highly Expressed Genes

The parasite Plasmodium falciparum, responsible for the most deadly form of human malaria, is one of the extremely AT-rich genomes sequenced so far and known to possess many atypical characteristics. Using multivariate statistical approaches, the present study analyzes the amino acid usage pattern in 5038 annotated protein-coding sequences in P. falciparum clone 3D7. The amino acid composition of individual proteins, though dominated by the directional mutational pressure, exhibits wide variation across the proteome. The Asn content, expression level, mean molecular weight, hydropathy, and aromaticity are found to be the major sources of variation in amino acid usage. At all stages of development, frequencies of residues encoded by GCrich codons such as Gly, Ala, Arg, and Pro increase significantly in the products of the highly expressed genes. Investigation of nucleotide substitution patterns in P. falciparum and other Plasmodium species reveals that the nonsynonymous sites of highly expressed genes are more conserved than those of the lowly expressed ones, though for synonymous sites, the reverse is true. The highly expressed genes are, therefore, expected to be closer to their putative ancestral state in amino acid composition, and a plausible reason for their sequences being GC-rich at nonsynonymous codon positions could be that their ancestral state was less AT-biased. Negative correlation of the expression level of proteins with respective molecular weights supports the notion that P. falciparum, in spite of its intracellular parasitic lifestyle, follows the principle of cost minimization