Curcumin ameliorates the targeted delivery of methotrexate intercalated montmorillonite clay to cancer cells.

Montmorillonite Clay (MMT) is aimed to develop as an orally administrable drug delivery vehicle with enhanced efficacy. Aiming to enhance the therapeutic index of methotrexate, curcumin is concomitantly used with methotrexate in the present study. Being folate antagonist in nature, methotrexate is internalized into cells by folate receptor (FR); which is over-expressed in certain human cancer cells such as cervical carcinoma cells (HeLa). Firstly, montmorillonite Clay (MMT) is organically modified (OMMT) with cetyl trimethyl ammonium bromide (CTAB) and used to intercalate curcumin and methotrexate separately, designated as OMMT-Cur and OMMT-MTX, respectively. XRD pattern demonstrated successful intercalation of therapeutics and an increase in clay interlayer distance facilitated by CTAB. The dissolution kinetics of methotrexate follows Higuchi model for both Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), while the release kinetics for curcumin fitted into Higuchi model for SGF and Hixson-Crowell model for SIF, respectively. OMMT-MTX are able to discriminate FR-positive HeLa cells from FR-negative breast cancer cells (MCF7); irrespective of alike cellular phenotypes. Further, the pre-treatment of HeLa cells with curcumin improves its sensitivity towards methotrexate causing a greater killing of the Hela cells. Together, the results propose the concomitant use of curcumin and methotrexate for successfully targeting highly invasive FR-positive carcinomas by means of folate receptor using MMTs.

Investigation of the Origin of Voltage Generation in Potentized Homeopathic Medicine through Raman Spectroscopy.

BACKGROUND: For the study of homeopathic medicines in proper perspective, emerging techniques in material science are being used. Vibrational spectroscopy is one such tool for providing information on different states of hydrogen bonding as an effect of potentization. The associated change in electrical properties is also correlated with this effect. OBJECTIVE: From the vibrational spectra, the changes in hydrogen bonding due to dilution followed by unidirectional vigorous shaking (together termed potentization) of 91% ethanol and two homeopathic medicines Chininum purum and Acidum benzoicum have been studied. The aim was to correlate the result with the change in the electrical properties of the system. METHODS: Raman spectroscopy was used to study the vibrational spectra. A U-shaped glass tube (electrochemical cell), where one arm contained bi-distilled water and the other arm alcohol/homeopathic medicine (the arms being separated by a platinum foil), was used to measure the voltage generated across two symmetrically placed platinum electrodes. RESULTS: For all samples, it was observed that potentization affected the intensity of OH stretching bands at the frequencies 3240 cm-1, 3420 cm-1 and 3620 cm-1, corresponding to strong hydrogen bond, weak hydrogen bond and broken hydrogen bond, respectively. With the increase in potency, in the presence and absence of the two medicines in ethanol, the number of OH groups linked by strong hydrogen bonds decreased, while the number of OH groups with weak hydrogen bonds increased. With the increase in potentization, the number of OH groups with broken hydrogen bonds showed a difference in the presence and absence of the medicine.The voltage measurements for ethanol show that, with succussion, the magnitude of voltage increased with the two medicines at lower potencies, but not at higher potency where the voltage is lower. Acidum benzoicum, which is acidic in nature, had higher voltage values (113mV, 130 mV and 118 mV at 6C, 30C and 200C, respectively), compared with Chininum purum, which is basic in nature (20 mV, 85 mV and 65 mV at 6C, 30C and 200C, respectively). CONCLUSION: The experimental results indicate a correlation between the vibrational and electrical properties of the homeopathic medicines Acidum benzoicum and Chininum purum at different potencies.

Synthesis and Property of Copper-Impregnated α-MnO2 Semiconductor Quantum Dots.

Because of the superior optical and electrical properties, copper-impregnated size tuneable high-temperature stable manganese dioxide semiconductor quantum dots (SQDs) have been successfully synthesized by a modified chemical synthesis technique. Their size-dependent dielectric properties, semiconducting properties, and current-voltage ( I- V) characteristics have been investigated. X-ray diffraction pattern and Raman spectra confirmed that the required phase is present. Because of the different sintering temperature tuneable size of SQDs has been found and confirmed by high-resolution transmission electron microscopy. The band gap energy of the material is found to be 1.25-1.67 eV, measured from Tauc plot using UV-vis absorbance spectrum and their semiconducting properties have been confirmed by the non linear current-voltage ( I- V) behavior. Most intense green emission peak of photoluminescence (PL) spectroscopy confirms the oxygen vacancy defect state. The stoke shifting of Raman spectra, UV absorption, and PL emission are the footprint of quantum confinement effect. Incorporation of a little amount of Cu in tetragonal hollandite structure of α-MnO2 generates strain within that structure. This leads to create sufficient crystal defect state as well as rise in dielectric constant accompanied with low dielectric loss and higher ac conductivity. All these highly desirable properties make the SQDs a potential candidate for developing multifunctional photo-electronic devices. Owing to the tuneable band gap and electronic transport of the SQDs, we realized that the controllable size paves the way for designing SQDs possessing unique properties for optical and electronic device applications. Using this material as a high dielectric separator, a high-performance supercapacitor has been successfully fabricated which can light up 15 light-emitting diodes for 47 min 23 s after charging them only for 30 s.

Effect of Homeopathic Dilutions of Cuprum Arsenicosum on the Electrical Properties of Poly(Vinylidene Fluoride-Co-Hexafluoropropylene).

BACKGROUND: We report the effects of nanoparticles in homeopathic preparations of copper salts on the electrical properties of polymer film. Previous work showed that the incorporation of metal-derived homeopathic medicines increases the dielectric constant and alternating current (AC) conductivity of an electroactive polymer film that is commonly used as a capacitor in the electronic industry.We report here the effect of dilution of one homeopathic medicine, Cuprum arsenicosum (CuAs), at 200C potency on the electrical properties of the polymer film of poly(vinylidene fluoride-co-hexafluoropropylene). METHODS: CuAs 200c was incorporated in the film by the solution casting method. The electrical characteristics were measured at different frequencies using an inductance, capacitance, and resistance meter. Fourier transform infrared spectroscopy (FTIR) was performed to detect phase change in the polymer film due to the incorporation of CuAs. Morphology and particle size were studied using field emission scanning electron microscopy (FESEM) and energy dispersive X-ray (EDX) spectroscopy. RESULTS: At 10 kHz frequency, both dielectric constant and AC conductivity increased approximately 18 times for the polymer film when incorporated with 2 mL CuAs at 200C potency. FTIR indicated the increase in conducting phase, while FESEM and EDX confirmed the presence of spherical CuAs particles. CONCLUSION: The incorporation of CuAs in the electroactive polymer film enhances the conductivity and dielectric constant. We conclude that these changes arise from the change in phase of the polymer film, and because of the presence of two different metals that affects the interfacial polarization.

A Bioinformatics approach to designing a Zika virus vaccine.

The Zika virus infections have reached epidemic proportions in the Latin American countries causing severe birth defects and neurological disorders. While several organizations have begun research into design of prophylactic vaccines and therapeutic drugs, computer assisted methods with adequate data resources can be expected to assist in these measures to reduce lead times through bioinformatics approaches. Using 60 sequences of the Zika virus envelope protein available in the GenBank database, our analysis with numerical characterization techniques and several web based bioinformatics servers identified four peptide stretches on the Zika virus envelope protein that are well conserved and surface exposed and are predicted to have reasonable epitope binding efficiency. These peptides can be expected to form the basis for a nascent peptide vaccine which, enhanced by incorporation of suitable adjuvants, can elicit immune response against the Zika virus infections.

Enhancement of quantum efficiency of a dye-sensitized electrochemical cell by using triturated zinc oxide mixed with two organic dyes, azure C and rose bengal

For efficiently utilising solar energy, when suitable nanoparticles are being engineered, triturated zinc oxide an eco-friendly, easily available, low-cost material has been used as an agent for solar energy conversion. Two organic dyes Azure C and Rose bengal having absorption bands in two different spectral regions at 545 nm and 610 nm respectively, were chosen in order to overcome the band absorption limits of each dye and utilise the broad spectrum of solar radiation. The material was mixed with these two dyes in a specially devised electrochemical cell and photovoltage with significant efficiency was generated. The energy conversion efficiency of the cell using three different potencies 6C, 30C and 200C of triturated zinc oxide with the same concentration of two dyes (0.5x10-5 M) in all cases are 0.39%, 0.43% and 0.35% respectively. The efficiency is only 0.15% for the mixed dye under similar conditions.

Effects of homeopathic medicine on physical properties of matter - a classical and QED perspective

Homeopathic medicines affect physical properties of matter which depend on the characteristic and the potency of the medicine1. These effects can be explained from two aspects: (a) classical and (b) quantum electrodynamical. Using three different sets of experiments where homeopathic medicines have affected the physical properties of matter, we have shown how the results can be interpreted from both these points of view. (AU)

Effect of ultrahigh diluted homeopathic medicines on the electrical properties of PVDF-HFP

In an effort to improve the electrical properties of the electroactive Poly(vinylidene fluoride-hexafluoropropylene) (PVdF-HFP), we introduced a novel and simple approach to synthesize PVDFHFP composite films by incorporating ultrahigh dilutions of two homeopathic medicines Ferrum metallicum (FM) and Zincum oxidatum (ZO) in different potencies. The homeo-PVDF-composite films (HPCF) were synthesized by simple solution casting technique. XRD, FESEM, FTIR studies were performed to check the presence of nanoparticles in the film. The electrical properties of the HPCF samples get enhanced significantly due to the incorporation of the medicines and the effect increases with the increase in potency of the medicines.

Effect of ultrahigh diluted homeopathic medicines on the electrical properties of PVDF-HFP

In an effort to improve the electrical properties of the electroactive Poly(vinylidene fluoridehexafluoropropylene) (PVdF-HFP), we introduced a novel and simple approach to synthesize PVDFHFP composite films by incorporating ultrahigh dilutions of two homeopathic medicines Ferrum metallicum (FM) and Zincum oxidatum (ZO) in different potencies. The homeo-PVDF-composite films (HPCF) were synthesized by simple solution casting technique. XRD, FESEM, FTIR studies were performed to check the presence of nanoparticles in the film. The electrical properties of the HPCF samples get enhanced significantly due to the incorporation of the medicines and the effect increases with the increase in potency of the medicines. (AU)

Diversity and evolution of the envelope gene of dengue virus type 1 circulating in India in recent times.

Dengue viral attacks have been reported in various parts of India in recent years. In this paper we report on our studies of the characterisation and evolutionary aspects of gene sequences of the envelope glycoprotein of the prevalent Indian dengue virus type 1. Comparison with sequences from other countries shows that the envelope genes identified in India are closely related to strains from Malaysia. From the evolutionary point of view the envelope gene sequences of this dengue virus of India for past few years show that a marked mutational shift in the nucleotide sequences of the envelope gene have taken place from around the year 2000. Also, phylogenetic relationship with other three sera of dengue virus reported in India from 2005 shows that the dengue virus 1 is more closely related to dengue viruses 3 and 4 and relatively distantly to dengue virus 2.

H7N9 influenza outbreak in China 2013: In silico analyses of conserved segments of the hemagglutinin as a basis for the selection of peptide vaccine targets.

The sudden emergence of a human infecting strain of H7N9 influenza virus in China in 2013 leading to fatalities in about 30% of the cases has caused wide concern that additional mutations in the strain leading to human to human transmission could lead to a deadly pandemic. It may happen in a short time span as the outbreak of H7N9 is more and more recurrent, which implies that H7N9 evolution is speeding up. H7N9 flu strains were not known to infect humans before this attack in China in February 2013 and it was solely an avian strain. While currently available drugs such as oseltamivir have been found to be largely effective against the H7N9, albeit with recent reported cases of development of resistance to the drug, there is a necessity to identify alternatives to combat this disease, especially if it assumes pandemic proportions. In our work, we have tried to investigate for the genetic changes in hemagglutinin (HA) protein sequence that lead to human infection by an avian infecting virus and identify possible peptide targets to design vaccines to control this upcoming risk. We identified three highly conserved regions in all H7 subtypes, of which one particular immunogenic surface exposed region was found to be well conserved in all human infecting H7N9 strains (accessed up to 27th March 2014). Compared to H7N9 avian strains, we identified two mutations in this conserved region at the receptor binding site of all post-February 2013 human-infecting H7N9China hemagglutinin protein sequences. One of the mutations is very close (3.6 Å) to the hemagglutinin sialic acid binding pocket that may lead to better binding to human host's sialic acid due to the changes in hydrophobicity of the microenvironment of the binding site. We found that the peptide region with these mutational changes that are specific for human infecting H7N9 virus possess the possibility of being used as target for a peptide vaccine.

In situ synthesis of Ni(OH)2 nanobelt modified electroactive poly(vinylidene fluoride) thin films: remarkable improvement in dielectric properties.

A facile and low cost synthesis of Ni(OH)2 nanobelt (NB) modified electroactive poly(vinylidene fluoride) (PVDF) thin films with excellent dielectric properties has been reported via in situ formation of Ni(OH)2 NBs in the PVDF matrix. The formation and morphology of the NBs are confirmed by UV-visible spectroscopy and field emission scanning electron microscopy respectively. A remarkable improvement in electroactive ß phase nucleation (∼82%) and the dielectric constant (ε ∼ 3.1 × 10(6) at 20 Hz) has been observed in the nanocomposites (NCs). The interface between the NBs and the polymer matrix plays a crucial role in the enhancement of the electroactive ß phase and the dielectric properties of thin films. Strong interaction via hydrogen bonds between Ni(OH)2 NBs and the PVDF matrix is the main reason for enhancement in ß phase crystallization and improved dielectric properties. The NC thin films can be utilized for potential applications as high energy storage devices like supercapacitors, solid electrolyte batteries, self-charging power cells, piezoelectric nanogenerators, and thin film transistors and sensors.

Effect of in situ synthesized Fe2O3 and Co3O4 nanoparticles on electroactive ß phase crystallization and dielectric properties of poly(vinylidene fluoride) thin films.

A simple and low cost in situ process has been developed to synthesize Fe2O3-Co3O4 nanoparticles (NPs) loaded poly(vinylidene fluoride) (PVDF) thin films. The electroactive ß phase nucleation mechanism and the dielectric properties of the films have been investigated by X-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry and using an LCR meter. Results confirmed that the electroactive ß phase crystallization in the PVDF matrix is due to the fast nucleating or catalytic effect of the in situ NPs. Homogenous dispersion of in situ Fe2O3-Co3O4 NPs in the polymer matrix leads to strong interfacial interaction between the NPs and the polymer resulting in enhanced ß phase nucleation in PVDF and a large dielectric constant of the thin films. The observed variation in the electroactive ß phase nucleation by NPs (Fe2O3-Co3O4) and the dielectric properties of the thin films have been explained on the basis of surface charge, size, geometrical shape and extent of agglomeration of the NPs in the polymer matrix.

Derivation of an empirical relation between the size of the nanoparticle and the potency of homeopathic medicines

Homeopathic medicines are often prescribed at very high dilutions and it is a clinically observed fact that the medicinal effect of the drug remains even at these high dilutions. The increase in potency of a medicine due to potentization is still debatable from physico-chemical point of view. Out of various hypotheses to explain this phenomenon, a recent hypothesis, advanced by us and supported by others, is that the size of the constituent particles decreases and eventually achieves nano dimension due to potentization. From the experiments performed by our group, the size of nanoparticles (NPs) of Cuprum metallicum, Zincum oxydatum, Aurum metallicum, Ferrum metallicum and Aconitum napellus (6cH, 30cH and 200cH) have been estimated. A general mathematical expression of the form y = a x-n has been derived which relates the size of NPs (y) with the corresponding potencies (x). There is no method to calculate the accurate potency of the homeopathic medicine, as the potency of a medicine depends to some extent on the method of preparation, for which a standardized procedure is warranted. Also, while handling a medicine, the solvent might evaporate causing a change in the potency. Thus by measuring the size of the NPs and using our proposed standard curve, the potency may be estimated...

Derivation of an empirical relation between the size of the nanoparticle and the potency of homeopathic medicines

Homeopathic medicines are often prescribed at very high dilutions and it is a clinically observed fact that the medicinal effect of the drug remains even at these high dilutions. The increase in potency of a medicine due to potentization is still debatable from physico-chemical point of view. Out of various hypotheses to explain this phenomenon, a recent hypothesis, advanced by us and supported by others, is that the size of the constituent particles decreases and eventually achieves nano dimension due to potentization. From the experiments performed by our group, the size of nanoparticles (NPs) of Cuprum metallicum, Zincum oxydatum, Aurum metallicum, Ferrum metallicum and Aconitum napellus (6cH, 30cH and 200cH) have been estimated. A general mathematical expression of the form y = a x-n has been derived which relates the size of NPs (y) with the corresponding potencies (x). There is no method to calculate the accurate potency of the homeopathic medicine, as the potency of a medicine depends to some extent on the method of preparation, for which a standardized procedure is warranted. Also, while handling a medicine, the solvent might evaporate causing a change in the potency. Thus by measuring the size of the NPs and using our proposed standard curve, the potency may be estimated. (AU)

In silico study of potential autoimmune threats from rotavirus infection.

Rotavirus, the major cause of infantile nonbacterial diarrhea, was found to be associated with development of diabetes-associated auto-antibodies. In our study we tried to find out further potential autoimmune threats of this virus using bioinformatics approach. We took rotaviral proteins to study similarity with Homo sapiens proteome and found most conserved structural protein VP6 matches at two regions with ryanodine receptor, an autoimmune target associated with myasthenia gravis. Myasthenia gravis, a chronic neurodegenerative autoimmune disorder with no typical known reason, is characterized by fluctuating muscle weakness which is typically enhanced during muscular effort. Affected patients generate auto antibodies against mainly acetyl choline receptor and sarcoplasmic reticulum calcium-release channel protein ryanodine receptor. Further, we observed that two regions which matched with ryanodine receptor remain conserved in all circulating rotaviral strains and showed significant antigenecity with respect to myasthenia gravis associated HLA haplotypes. Overall, our study detected rotaviral VP6 as a potential threat for myasthenia gravis and enlighten an area of virus associated autoimmune research.

Characteristics of influenza HA-NA interdependence determined through a graphical technique.

Influenza viruses are characterized by two surface proteins - the hemagglutinin (HA) of which there are 16 varieties, and the neuraminidase (NA) of which there are 9, each subtype characterized by its antigenic properties. Although theoretically 16 x 9 combinations are possible, only a few like the H1N1, H3N2, etc are seen to occur more frequently. Numerous studies with select subtypes like H1N1, H5N1, etc., have explained this phenomena by indicating that viral viability necessitates functional balance between the NA and HA so that only some combinations are favored. However, the reasons for this balance or its characteristics and whether this is universal for influenza subtypes are not yet known. Using novel graphical techniques and hypothesizing a coupling between the HA and NA, we devised a coupling factor to estimate the interdependence, if any, between HA and NA sequences covering a global sample of 10 subtypes and 164 sequences. We found that (a) the coupling we hypothesized between HAs and NAs is characteristic of each subtype, (b) within each subtype the coupling value is significantly different for human infecting strains and those that infect avians, and (c) artificial strains made up by mixing and matching HAs and NAs from different subtypes produce coupling factors that are far from the characteristic values for the parent subtype indicating possibly non-viable viruses, a result that matches with experimental evidence of Zhang et al. [1]. We also show that some natural strains that did not fit the characteristic values for its subtype could have been possible mismatches during viral packaging. Our observations have important consequences for drug and vaccine design and for monitoring of influenza virus reassortments and possible evolution of human pandemics.

In situ synthesis and antibacterial activity of copper nanoparticle loaded natural montmorillonite clay based on contact inhibition and ion release.

Copper nanoparticle based clay composite has been synthesized by in situ reduction of a copper ammonium complex ion and characterized by different analytical instruments. The copper nanoparticles were both intercalated and adsorbed on the surface with diameters of <5nm (for intercalated) and 25-30nm (for adsorbed). The composite showed good stability for over 3 months in air. Excellent antimicrobial activity of the composite was observed on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Enterococcus faecalis with mortality rates >90% after 12h. Cellular membrane damage permeated by direct attachment of the composite and indirect damage caused by released copper ion are the primary sources of antibacterial action. Cytotoxicity measurements showed minimal adverse effect on the two human cell lines beyond the M.B.C. value for the microorganisms studied. In the present form the clay composite shows good promise for use in therapeutic applications.

In silico study of rotavirus VP7 surface accessible conserved regions for antiviral drug/vaccine design.

BACKGROUND: Rotaviral diarrhoea kills about half a million children annually in developing countries and accounts for one third of diarrhea related hospitalizations. Drugs and vaccines against the rotavirus are handicapped, as in all viral diseases, by the rapid mutational changes that take place in the DNA and protein sequences rendering most of these ineffective. As of now only two vaccines are licensed and approved by the WHO (World Health Organization), but display reduced efficiencies in the underdeveloped countries where the disease is more prevalent. We approached this issue by trying to identify regions of surface exposed conserved segments on the surface glycoproteins of the virion, which may then be targeted by specific peptide vaccines. We had developed a bioinformatics protocol for these kinds of problems with reference to the influenza neuraminidase protein, which we have refined and expanded to analyze the rotavirus issue. RESULTS: Our analysis of 433 VP7 (Viral Protein 7 from rotavirus) surface protein sequences across 17 subtypes encompassing mammalian hosts using a 20D Graphical Representation and Numerical Characterization method, identified four possible highly conserved peptide segments. Solvent accessibility prediction servers were used to identify that these are predominantly surface situated. These regions analyzed through selected epitope prediction servers for their epitopic properties towards possible T-cell and B-cell activation showed good results as epitopic candidates (only dry lab confirmation). CONCLUSIONS: The main reasons for the development of alternative vaccine strategies for the rotavirus are the failure of current vaccines and high production costs that inhibit their application in developing countries. We expect that it would be possible to use the protein surface exposed regions identified in our study as targets for peptide vaccines and drug designs for stable immunity against divergent strains of the rotavirus. Though this study is fully dependent on computational prediction algorithms, it provides a platform for wet lab experiments.

Antimicrobial efficacy and biocompatibility study of copper nanoparticle adsorbed mullite aggregates.

A mullite based antimicrobial ceramic composite has been developed by simple adsorption of copper nano particle suspension. The physico-chemical properties of samples were characterized by different instruments which showed that the composite is well crystalline with homogeneous distribution of copper nanoparticles on the surface. Antimicrobial study was performed by plate count technique which showed >99% mortality for all the bacterial species studied after 24h of incubation. Minimum inhibitory concentration (MIC) values determined by batch culture process showed considerably low values (in terms of copper content) indicating that mullite matrix plays a role in enhancing the antimicrobial efficacy of the composite. Biocompatibility studies on human cancer cell lines indicated that the composite had negligible toxicity below 100µg/mL of Cu content. Thus the composite can be suitable for developing antimicrobial ceramic wares and therapeutic purposes like treatment of variety of microbial infections.