Padma Thiagarajan

Anticancer activity of Ophiobolin A, isolated from the endophytic fungus Bipolaris setariae.

Abstract The present work describes the anticancer activity of Ophiobolin A isolated from the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using preparative HPLC and its structure was confirmed by HRMS, 1H NMR, 13C NMR, COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell proliferation with IC50 of 0.4–4.3 μM. In comparison, IC50 against normal cells was 20.9 μM. It was found to inhibit the phosphorylation of S6 (IC50 = 1.9 ± 0.2 μM), ERK (IC50 = 0.28 ± 0.02 μM) and RB (IC50 = 1.42 ± 0.1 μM), the effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells with concomitant inhibition of signalling proteins. Thus, this study reveals that anticancer activity of Ophiobolin A is associated with simultaneous inhibition of multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB. Graphical abstract

Combating drug resistant pathogenic bacteria isolated from clinical infections, with silver oxide nanoparticles

The antibiogram study of methicillin resistant Staphylococcus aureus isolates revealed 100% resistance to vancomycin, bacitracin, erythromycin, ciprofloxacin and nalidixic acid. Eight isolates (53.3%) showed resistance to co-trimoxazole and one isolate to rifampicin, which was the drug of choice. An effort was made to evaluate the antimethicillin resistant Staphylococcus aureus activity of silver oxide (Ag2O) nanoparticles synthesized from Aspergillus terreus VIT 2013. Production of Ag2O nanoparticles was confirmed by color change of fungal filtrate and UV light absorption at 450 nm. X-ray diffraction pattern showed 2θ values at 27, 32, 38 and 57°, which corresponded to the cubic structure of Ag2O nanocrystals. Fourier transform infrared spectroscopy indicated the presence of primary amine, carbonyl group, NO2 and silver, revealing protein mediated nanoparticle production. The scanning electron microscope image showed freely dispersed Ag2O nanoparticles. The nanoparticles were active against all methicillin resistant isolates and hence can be used as antibacterial agents against drug resistant bacteria.

Profiling Deleterious Non-synonymous SNPs of Smoker's Gene CYP1A1

CYP1A1 gene belongs to the cytochrome P450 family and is known better as smokers’ gene due to its hyperactivation as a consequence of long term smoking. The expression of CYP1A1 induces polycyclic aromatic hydrocarbon production in the lungs, which when over expressed, is known to cause smoking related diseases, such as cardiovascular pathologies, cancer, and diabetes. Single nucleotide polymorphisms (SNPs) are the simplest form of genetic variations that occur at a higher frequency, and are denoted as synonymous and non-synonymous SNPs on the basis of their effects on the amino acids. This study adopts a systematic in silico approach to predict the deleterious SNPs that are associated with disease conditions. It is inferred that four SNPs are highly deleterious, among which the SNP with rs17861094 is commonly predicted to be harmful by all tools. Hydrophobic (isoleucine) to hydrophilic (serine) amino acid variation was observed in the candidate gene. Hence, this investigation aims to characterize a candidate gene from 159 SNPs of CYP1A1.

Umbilical cord stem cells: A review

Stem cells are the future of the regenerative medicines. Stem cells are having the capacity for differentiation and self-renewal which makes it different from other cells. The umbilical cord is one of the rich sources of stem cells. These stem cells are collected during the postnatal period. It can give three types of cells-hematopoietic stem cells, mesenchymal stem cells, and non-hematopoietic multipotent stem cells. Cord blood cells can be stored in cord blood bank and can be used whenever required. Umbilical cord stem cells can treat various dreadful diseases. They are used for the treatment of cancer, neurodegenerative disease, and blood-borne diseases. Umbilical cord stem cells can be used for various clinical applications. Cord stem cells have many therapeutic uses, and future research and studies in this area are requiredin order to exploit the full potential of stem cells for the benefit of mankind. In this review, we have tried to highlight some basic features of umbilical cord stem cells along with its isolation, proliferation, identification, and differentiation. We have focussed mainly on the hematopoietic and mesenchymal stem cells as much work on the non-hematopoietic multipotent stem cells has not been done. We have also discussed about the therapeutic future of the umbilical cord stem cells.

Formulation and characterization of a Helianthus annuus - alkyl polyglucoside emulsion cream for topical applications

Green formulations with herbal oils and natural nonionic emulsifiers project several advantages, like favorable viscosity profiles, for use as topical applicants. Their inherent constituents also protect the skin against free radical damage and lipid peroxidation. They may hence serve as alternatives for synthetic chemical‐based formulations.

A Flaxseed Oil emulgel formulation for Prospective Food Applications Synthesis and Characterization

Plant oil formulations have been effective for the production of encapsulating systems that could be used for the oral delivery of various bioactives to achieve nutritive and therapeutic effects. These kinetically stable formulations prevent the degradation of such actives and also enhance their bioavailability. In this context, synthesis of a flaxseed oil-alkyl polyglucoside based formulation was carried out and its ultrasonication under a set of optimized conditions was employed to reduce the particle size of this emulsion. The ultrasonication conditions were optimized with respect to duty cycle, time, cavitation intensity and amplitude. Physiochemical characterization and FAME analysis of the oil were carried out. The final formulation was characterized for particle size, zeta potential and electrophoretic mobility. FTIR spectra identified different functional groups in the base constituents and also the presence of extensive hydrogen bonding in the formulation. Its SEM analysis showed well dispersed oil globules in water. The rheological studies of the formulations with respect to relevant parameters like hysteresis loop areas, yield stress, consistency and pseudoplasticity indices revealed non-Newtonian thixotropic behavior and shear thinning feature that contribute to good flow characteristics. Thus, it is inferred that this formulation could serve as an excellent base matrix for potential food applications.

Selection of a design for response surface

Box-Behnken, Central-Composite, D and I-optimal designs were compared using statistical tools. Experimental trials for all designs were generated. Random uniform responses were simulated for all models. R-square, Akaike and Bayesian Information Criterion for the fitted models were noted. One–way ANOVA and Tukeys multiple comparison test were performed on these parameters. These models were evaluated based on the number of experimental trials generated in addition to the results of the statistical analyses. D-optimal design generated 12 trials in its model, which was lesser in comparison to both Central Composite and Box-Behnken designs. The R-square values of the fitted models were found to possess a statistically significant difference (P<0.0001). D-optimal design not only had the highest mean R-square value (0.7231), but also possessed the lowest means for both Akaike and Bayesian Information Criterion. The D-optimal design was recommended for generation of response surfaces, based on the assessment of the above parameters.

A green Hibiscus cannabinus oil emollient cream for potential topical applications

A green emollient cream with Hibiscus cannabinus seed oil and an alkyl polyglucoside surfactant has been formulated. It can serve as biological alternatives to synthetic formulations that normally incorporate chemical constituents as surfactants and stabilizers mainly to increase consumer compliance in terms of textural and visual aesthetics. FAME analysis of the oil showed the presence octanoic and decanoic acids. The cream after formulation and ultrasonication, presented a smooth and soft appearance with visual and textural appeal. It showed a mean particle size of 138 nm with a zeta potential of -59.2 mV and an electrophoretic mobility of 0.000459 cm2/Vs. Its SEM image projected well dispersed oil globules in water. FTIR spectrum showed extensive hydrogen bonding. Accelerated stability tests under conditions of freeze thawing, heating cooling and centrifugation revealed no cracking, creaming or phase separation. Similar results were observed during the shelf life studies. It is concluded that this Hibiscus cannabinus cream can be utilized as an emollient base for loading cosmopharmaceutic ingredients for their topical delivery, without any toxicity concerns, as it is formulated from completely natural constituents.

Combination effects of sorafenib with PI3K inhibitors under hypoxia in colorectal cancer

Aim This study reports the influence of hypoxia on response of colorectal cancer cells to anticancer effects of sorafenib in combination with PI3K inhibitors GDC-0941 and BEZ-235. Materials and methods All hypoxic exposures were carried out at 1% O2/5% CO2. Antiproliferation activity was evaluated by 48 hours propidium iodide and 14 days clonogenic assay. Protein levels were evaluated by fluorescence ELISA. Metabolites lactate and glucose were evaluated biochemically. Results In the 48-hour proliferation assay, sorafenib acted synergistically with GDC-0941 but not with BEZ-235. In long-term colony-forming assays, both GDC-0941 and BEZ-235 were shown to potentiate the antiproliferative activity of sorafenib. At the molecular level, the synergism is mediated through inhibition of pAKT, pS6, p4EBP1, pERK, cyclin D1, and Bcl-2. No change in hypoxia-inducible factor-1α (HIF-1α) levels was observed in cells treated with the combination of compounds under hypoxia. A significant reduction in glucose uptake and lactate release was observed in cells treated with the combination of compounds under normoxia and hypoxia. Conclusion Combinations of sorafenib with PI3K inhibitors BEZ-235 and GDC-0941 are efficacious under hypoxia. Thus, these anticancer combinations have a potential to overcome the hypoxia-mediated resistance mechanisms to antiproliferative agents in cancer therapy.