Preparation of superparamagnetic iron oxide/doxorubicin loaded chitosan nanoparticles as a promising glioblastoma theranostic tool

Theranostic nanoparticles (NPs) are promising for opening new windows toward personalized disease management. Using a single particle capable of both diagnosis and drug delivery, is the major benefit of such particles. In the present study, chitosan NPs were used as a dual action carrier for doxorubicin (DOX; chemotherapeutic agent) and superparamagnetic iron oxide nanoparticles (SPIONs; imaging agent). SPIONs and DOX were loaded at different concentrations within poly-l -arginine-chitosan-triphosphate matrix (ACSD) using the ionic gelation method. NPs’ size were in the range of 184.33 ± 4.4 nm. Drug release analysis of DOX loaded NPs (NP-DOX) showed burst release at pH 5.5 (as in tumor environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release profile. NP-DOX internalization was confirmed by flowcytometry and fluorescent microscopy. Uptake process results were corroborated by accumulation of drug in the intracellular space. Iron content was evaluated by inductively coupled plasma and prussian blue staining. In vitro magnetic resonance imaging (MRI) showed a decline in T ₂ relaxation times by increasing iron concentration. MRI analysis also confirmed uptake of NPs at the optimum concentration in C6 glioma cells. In conclusion, ACSD NPs could be utilized as a promising theranostic formulation for both diagnosis and treatment of glioblastoma.     

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress,autophagy and apoptosis

The interplay between H₂S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide-a donor of H ₂S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+ L -NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N-acetyl-b-glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω-nitro-l-arginine methyl ester ( L -NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H ₂S in the kidney. Moreover, the study suggests that NO, in an isoform-dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD.     

Investigation of TiO2 anatase (1 0 1), (1 0 0) and (1 1 0) facets as immobilizer for a potential anticancer RNA aptamer: a classical molecular dynamics simulation

One of the most outstanding properties of TiO₂ nanosheets is their lack of harmful effects on the public health and environment, which makes them an appropriate agent for medical applications such as drug delivery. Interaction of an RNA aptamer with (1 0 1), (1 0 0) and (1 1 0) surfaces of TiO₂ anatase were investigated using the molecular dynamics simulation. The structural parameters including root-mean-square deviation and fluctuation, and the distance between the center-of-mass of RNA aptamer and the considered surfaces were discussed in detail. Besides, the effect of water between adsorbed aptamer and surface was investigated and analyzed by the help of dipole moment orientation, hydrogen bonds and density profile of these water molecules. Analysis of the structural parameters and interaction energies shows that the (1 1 0) surface is energetically more favorable for the adsorption of considered RNA aptamer than the (1 0 0) and (1 0 1) surfaces. Consequently, our results suggest a great potential of (1 1 0) surface of TiO₂ as an efficient candidate for drug delivery applications.     

Use of artificial neural networks for analysis of the factors affecting particle size in mebudipine nanoemulsion

In this study, a nanoemulsion containing mebudipine [composed of ethyl oleate (oil phase), Tween 80 (T80), Span 80 (S80) (surfactants), polyethylene glycol 400, ethanol (cosurfactants), and deionized water] was prepared with the aim of improving its bioavailability for an effective antihypertensive therapy. Particle size of the formulation was measured by dynamic light scattering. Then, artificial neural networks were used in identifying factors that influence the particle size of the nanoemulsion. Three variables, namely, amount of surfactant system (T80?+?S80), amount of polyethylene glycol, and amount of ethanol as cosurfactants, were considered as input values and the particle size was used as output. The developed model showed that all the three inputs had some degrees of effect on particles size: increasing the value of each input decreased the size. Furthermore, amount of surfactant was found to be the dominant factor in controlling the final particle size of nanoemulsion.

Communicated by Ramaswamy H. Sarma     

Precise detection and tracing of Trichoderma hamatum 382 in compost-amended potting mixes by using molecular markers

Randomly amplified polymorphic DNA (RAPD) analysis and the PCR assay were used in combination with dilution plating on a semiselective medium to detect and enumerate propagules of Trichoderma hamatum 382, a biocontrol agent utilized in compost-amended mixes. Distinct and reproducible fingerprints were obtained upon amplification of purified genomic DNA of T. hamatum 382 with the random primers OPE-16, OPH-19, and OPH-20. Three amplified DNA fragments of 0.35 (OPE-16(0.35)), 0.6 (OPH-19(0.6)), and 0.65 (OPH-20(0.65)) kb were diagnostic for T. hamatum 382, clearly distinguishing it from 53 isolates of four other Trichoderma spp. tested. Some isolates of T. hamatum shared these low-molecular-weight fragments with T. hamatum 382. However, RAPD analysis of isolates of T. hamatum with all three random primers used in consecutive PCR tests distinguished T. hamatum 382 from other isolates of T. hamatum. These three RAPD amplicons were cloned and sequenced, and pairs of oligonucleotide primers for each cloned fragment were designed. Use of the primers in the PCR assay resulted in the amplification of DNA fragments of the same size as the cloned RAPD fragments from genomic DNA of T. hamatum 382. A combination of dilution plating on a semiselective medium for Trichoderma spp. and PCR, with the RAPD primers OPH-19, OPE-16, and OPH-20 or the three sequence-characterized primers, was used successfully to verify the presence of T. hamatum 382 propagules in nine different soil, compost, and potting mix samples. All 23 Trichoderma isolates recovered on semiselective medium from commercial potting mixes fortified with T. hamatum 382 were identified as T. hamatum 382, whereas 274 Trichoderma isolates recovered from the other nine samples were negative in the PCR assay. Thus, this highly specific combination of techniques allowed detection and enumeration of propagules of T. hamatum 382 in fortified compost-amended potting mixes. Sequence-characterized amplified region markers also facilitated the development of a very simple procedure to amplify DNA of T. hamatum 382 directly from fortified compost-amended potting mixes.     

Neem leaves as a source of fertilizer-cum-pesticide vermicompost

Vermicomposting of neem (Azadirachta indica A. Juss) was accomplished in "high-rate" reactors operated at the earthworm (Eudrilus eugeniae) densities of 62.5 and 75 animals per litre of reactor volume. Contrary to the fears that neem--a powerful nematicide--might not be palatable to the annelids, the earthworms fed voraciously on the neem compost, converting upto 7% of the feed into vermicompost per day. Indeed the worms grew faster and reproduced more rapidly in the neem-fed vermireactors than in the reactors fed with mango leaf litter earlier studied by the authors (Gajalakshmi et al., 2003). Another set of experiments on the growth, flowering, and fruition of brinjal (Solanum melongena) plants with and without fertilization with vermicompost, revealed that the vermicompost had a significantly beneficial impact.     

Phenolic glyscosides, a new class of human recombinant nucleotide pyrophosphatase phosphodiesterase-1 inhibitors

Cytotoxicity and kinetic studies of phenolic glycosides, benzoyl salireposide (1) and salireposide (2), isolated from Symplocos racemosa, were performed against phosphodiesterase I enzyme from snake venom and human nucleotide pyrophosphatase phosphodiesterase-1. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both enzymes. K(i) Values of compounds 1 and 2 were found to be 360 and 1000 microM, respectively, against human nucleotide pyrophosphatase phosphodiesterase, and 525 and 1100 microM, respectively, against snake venom phosphodiesterase. IC(50) values of compounds 1 and 2 are 90 microM +/- 0.04 and 383 microM +/- 0.03, respectively, against human nucleotide pyrophosphatase phosphodiesterase and 171 microM +/- 0.02 and 544 microM +/- 0.021, respectively, against snake venom phosphodiesterase. Both compounds were found to be nontoxic up to concentration of 500 microM/mL as >90% cells were viable after 3 h of incubation. These compounds are potential candidates for the therapy of arthritis.