Gelatin-lecithin-F127 gel mediated self-assembly of curcumin vesicles for enhanced wound healing.

Curcumin, a principal component of Curcuma longa, has a long history of being used topically for wound healing. However, poor aqueous solubility of curcumin leads to poor topical absorption. Recently, gelatin based gel has been reported to overcome this issue. However, the release of curcumin from gelatin gel in the bioavailable or easily absorbable form is still a challenge. The present study reports the development of a composite gel prepared from gelatin, F127 and lecithin using temperature dependant gelation and loading of curcumin within it. Notably, the composite gel facilitated the release of curcumin entrapped within vesicles of ~400 nm size. Further, the composite gel exhibited increase in the storage modulus or gel strength, stability, pore size and hydrophobicity as compared to only gelatin gel. Finally, wound healing assay in murine model indicated that curcumin delivered through composite gel showed a significantly faster healing as compared to that delivered through organic solvent. This was also validated by histopathological and biochemical analysis showing better epithelization and collagen synthesis in the group dressed with curcumin containing composite gel. In conclusion, composite gel facilitated the release of bioavailable or easily absorbable curcumin which in turn enhanced the wound healing.

Antibiotic-Induced Gut Microbiota Depletion Accelerates the Recovery of Radiation-Induced Oral Mucositis in Rats.

PURPOSE: Due to its pivotal role in the modulation of immune and inflammatory responses, the gut microbiota has emerged as a key modulator of cancer treatment-induced gastrointestinal mucositis. However, it is not clear yet how it affects radiation therapy-induced oral mucositis (OM). As such, this study aimed to explore the gut microbiota's role in the pathogenesis of radiation-induced OM in rats. METHODS AND MATERIALS: Male Sprague Dawley rats were treated with 20 Gy x-ray radiation (Rx) delivered to the snout, with or without antibiotic-induced microbiota depletion (AIMD). OM severity was assessed, and tongue tissues were collected on day 9 and 15 postradiation for tissue injury and inflammatory markers assessment. RESULTS: AIMD+Rx had a significantly shorter duration of severe OM compared with Rx alone group. Macroscopically, the tongue ulcer-like area was smaller in AIMD+Rx compared with the Rx group. Microscopically, a smaller percentage of the mucosal ulcer was observed in the dorsal tongue of AIMD+Rx compared with the Rx group. AIMD+Rx also had significantly lower levels of interleukin 6, interleukin 1 beta, and toll like receptor 4 in the tongue tissues than the Rx group. CONCLUSIONS: The gut microbiota plays a role in OM pathogenesis, mainly in the recovery phase, through the modulation of proinflammatory pathways. Future microbiota-targeted interventions may improve OM in clinical settings.

Design strategies and evolving role of biomaterial assisted treatment of osteosarcoma.

Osteosarcoma is the most commonly diagnosed form of bone cancer. It is characterized by a high risk of developing lung metastasis as the disease progresses. Standard treatment includes combination of surgical intervention, chemotherapy and radiotherapy. However, the non-specificity of potent chemotherapeutic agents often leads to major side effects. In this review, we discuss the role of various classes of biomaterials, including both organic as well as inorganic in realizing the local and systemic delivery of therapeutic agents like drugs, radioisotopes and even gene silencing agents to treat osteosarcoma. Biomaterial assisted unconventional therapies such as targeted therapy, nanotherapy, magnetic hyperthermia, gene therapy, photothermal and photodynamic therapies are also being explored. A wide variety of biomaterials including lipids, carbon-based materials, polymers, silica, bioactive glass, hydroxyapatite and metals are designed as delivery systems with the desired loading efficiency, release profile, and on-demand delivery. Among others, liposomal carriers have attracted a great deal of attention due to their capability to encapsulate both hydrophobic and hydrophilic drugs. Polymeric systems have high drug loading efficiency and stability and can even be tailored to achieve desired size and physiochemical properties. Carbon-based systems can also be seen as an upcoming class of therapeutics with great potential in treating different types of cancer. Inorganic materials like silica nanoparticles have high drug payload owing to their mesoporous structure. On the other hand, ceramic materials like bioactive glass and hydroxyapatite not only act as excellent delivery vectors but also participate in osteo-regeneration activity. These multifunctional biomaterials are also being investigated for their theranostic abilities to monitor cancer ablation. This review systematically discusses the vast landscape of biomaterials along with their challenges and respective opportunities for osteosarcoma therapy.

Development of surface functionalized hydroxyapatite nanoparticles for enhanced specificity towards tumor cells.

Nanoparticles coupled with targeting moieties have attracted a great deal of attention for cancer therapy since they can facilitate site-specific delivery of drug and significantly limit the side effects of systemic chemotherapy. In this study, our aim is to develop surface functionalized hydroxyapatite nanoparticles, which could provide binding sites for a cancer cell targeting ligand, folic acid (FA) as well as an anticancer drug, doxorubicin hydrochloride (DOX). In order to attain dual functionalities, hydroxyapatite nanoparticles were functionalized with gelatin molecules. Gelatin, being a protein has both carboxyl and amine moieties, which makes it suitable for binding of DOX and FA. FA was chemically conjugated to the nanoparticles through an EDCNHS coupling reaction. The formation of single-phase hydroxyapatite nanostructure was ascertained by X-ray diffraction studies and the presence of organic moieties on the surface of nanoparticles was evident from Fourier transform infrared spectroscopy, thermogravimetric analysis and U.V.-visible spectroscopy. The FA-conjugated nanoparticles (FA-Gel-HANPs) showed high affinity towards DOX and pH-responsive sustained release of drug with higher release rate under acidic pH conditions, desired for cancer therapy. The FA-Gel-HANPs showed negligible cytotoxicity towards different cell lines (HepG2, WEHI-164, KB, WI-26 VA4 and WRL-68). However, DOX loaded nanoparticles (DOX-FA-Gel-HANPs) exhibited significant toxicity towards these cells, which was however highest in folate receptor (FR)-overexpressing, KB cells. These results were correlated with enhanced cellular uptake of DOX-FA-Gel-HANPs in KB cells in comparison to FR-deficient, WRL-68 cells studied by confocal laser scanning microscopy and flow cytometry. Moreover, cell cycle analysis in KB cells, showed higher sub-G1 population, indicating apoptosis as one of the cell death mechanisms. Overall, this study suggests that DOX-FA-Gel-HANPs could serve as a promising tumor-targeted drug delivery system.

A simple atomic beam oven with a metal thermal break.

We report the design and construction of a simple, easy to machine high temperature oven for generating an atomic beam in laser cooling experiments. This design eliminates the problem of thermal isolation of the oven region from the rest of the vacuum system without using a glass or ceramic thermal break. This design simplifies the construction and operation of high temperature ovens for elements having low vapor pressure. We demonstrate the functionality of such a source for strontium (Sr) atoms. We generate a high flux of Sr atoms for use in laser cooling and trapping experiments. The optimization of the design of the metal thermal break is done using a finite element analysis.

Bioadhesive polymeric film-based integrative platform for the unidirectional carbamazepine release from a volatile microemulsion.

Carbamazepine (CBZ) shows inconsistent absorption primarily due to its poor dissolution rate. In this study, we describe a bioadhesive polymeric film, embedded with microemulsion (ME), as a tool to enable improved CBZ dissolution and achieve sustained release. The ME was formulated using pseudo-ternary components; water, oil (n-butyl acetate), surfactant (tocopheryl polyethylene glycol 1000 succinate, TPGS) and cosurfactant (1,4-butanediol). The region at surfactant to co-surfactant ratio of 1:1 was characterized using dynamic light scattering, small angle neutron scattering and differential scanning calorimetry. Scattering studies showed that size distribution did not change upon water addition and temperature. Optimized ME composition containing CBZ was embedded into bioadhesive films composed with a backing layer. We successfully demonstrate the confinement of CBZ-ME into the film matrix and thereupon, the achievement of unidirectional sustained drug release up to 8 h. Our further investigations are directed over testing the system for localized drug delivery applications.

Trauma-induced Focal Nodular Mucinoses: A Rare Entity.

Cutaneous mucinoses refer to disorders with abnormal accumulation of mucin in the skin. Mucin is an amorphous material that is a part of the extracellular matrix in dermis. Cutaneous mucinoses could be primary or secondary. The latter is associated with systemic disorders such as autoimmune diseases, diabetes mellitus, paraproteinemia, or altered thyroid function. Here, we report an adult female patient with trauma-induced cutaneous focal nodular mucinoses on left-sided scapular region. Histology showed replacement of collagen bundles by mucinous deposits in superficial and mid-dermis. Mucinous substance was present in peri-eccrine location on Alcian blue staining.

Mutilating Keratoderma with Concomitant Alopecia and Keratoses Follicularis Spinulosa Decalvans: X-Linked Olmsted Syndrome and its Response to Isotretinoin.

We report a case of mutilating keratoderma with alopecia and keratoses follicularis spinulosa decalvans (KFSD), which was initially diagnosed as ectodermal dysplasia and Olmsted syndrome but was revisited as a case of X-linked Olmsted (XLO) syndrome. We focus on this uncommon entity (XLO) to highlight the differentials of alopecia with palmoplantar keratoderma.

PEG coated vesicles from mixtures of Pluronic P123 and l-α-phosphatidylcholine: structure, rheology and curcumin encapsulation.

PEG coated vesicles are important vehicles for the passive targeting of anticancer drugs. With a view to prepare PEG decorated vesicles using co-assembly of block copolymers and lipids, here we investigated the microstructure of aggregates formed in mixtures comprising lipids (l-α-phosphatidylcholine) and block copolymers (Pluronic P123), in the polymer rich regime. DLS and SANS studies show that the structure of the aggregates can be tuned from micelles to rod-like micelles or vesicles by changing the lipid to polymer composition. Rheological studies on gels formed by mixtures of polymer and lipid suggest incorporation of the lipid into the polymer matrix. The encapsulation efficiencies of polymer incorporated liposomes for curcumin and doxorubicin hydrochloride (DOX) are evaluated at different drug to carrier ratios. The pH dependent sustained release of both the drugs from the PEGylated liposomes suggests their application in the development of cost effective formulations for anticancer drug delivery.

Propionibacterium acnes and the Th1/Th17 Axis, Implications in Acne Pathogenesis and Treatment.

Acne vulgaris is one of the most commonly seen conditions and the immunological link is a topic of active research. Recently, the Th17 pathway has been found to play a pivotal role in acne. The adaptive immune response toward Propionibacterium acnes leads to activation of Th17 axis. Consequently, the Th17 cytokines (IL-17, IL-1 ß, IL-6, and tumor growth factor, in turn, activate the various pathogenic steps in acne. Drugs such as Vitamin D3 and isotretinoin which target the Th17 pathway may offer an additional pathway for their therapeutic response.

Inhomogeneous Poisson process rate function inference from dead-time limited observations.

The estimation of an inhomogeneous Poisson process (IHPP) rate function from a set of process observations is an important problem arising in optical communications and a variety of other applications. However, because of practical limitations of detector technology, one is often only able to observe a corrupted version of the original process. In this paper, we consider how inference of the rate function is affected by dead time, a period of time after the detection of an event during which a sensor is insensitive to subsequent IHPP events. We propose a flexible nonparametric Bayesian approach to infer an IHPP rate function given dead-time limited process realizations. Simulation results illustrate the effectiveness of our inference approach and suggest its ability to extend the utility of existing sensor technology by permitting more accurate inference on signals whose observations are dead-time limited. We apply our inference algorithm to experimentally collected optical communications data, demonstrating the practical utility of our approach in the context of channel modeling and validation.

Nonexponential Decoherence and Subdiffusion in Atom-Optics Kicked Rotor.

Quantum systems lose coherence upon interaction with the environment and tend towards classical states. Quantum coherence is known to exponentially decay in time so that macroscopic quantum superpositions are generally unsustainable. In this work, slower than exponential decay of coherences is experimentally realized in an atom-optics kicked rotor system subjected to nonstationary Lévy noise in the applied kick sequence. The slower coherence decay manifests in the form of quantum subdiffusion that can be controlled through the Lévy exponent. The experimental results are in good agreement with the analytical estimates and numerical simulations for the mean energy growth and momentum profiles of an atom-optics kicked rotor.

A compact atomic beam based system for Doppler-free laser spectroscopy of strontium atoms.

We report the construction of a simple, light weight, and compact atomic beam spectroscopy cell for strontium atoms. The cell is built using glass blowing technique and includes a simple titanium sublimation pump for the active pumping of residual and background gases to maintain ultra-high vacuum. A commercially available and electrically heated dispenser source is used to generate the beam of Sr atoms. We perform spectroscopy on the 5s2S01→5s 5pP11 transition to obtain a well resolved Doppler free spectroscopic signal for frequency stabilization of the laser source. This design can be easily extended to other alkali and alkaline earth metals.

Zealotry promotes coexistence in the rock-paper-scissors model of cyclic dominance.

Cyclic dominance models, such as the classic rock-paper-scissors (RPS) game, have found real-world applications in biology, ecology, and sociology. A key quantity of interest in such models is the coexistence time, i.e., the time until at least one population type goes extinct. Much recent research has considered conditions that lengthen coexistence times in an RPS model. A general finding is that coexistence is promoted by localized spatial interactions (low mobility), while extinction is fostered by global interactions (high mobility). That is, there exists a mobility threshold which separates a regime of long coexistence from a regime of rapid collapse of coexistence. The key finding of our paper is that if zealots (i.e., nodes able to defeat others while themselves being immune to defeat) of even a single type exist, then system coexistence time can be significantly prolonged, even in the presence of global interactions. This work thus highlights a crucial determinant of system survival time in cyclic dominance models.

Effect of zealotry in high-dimensional opinion dynamics models.

Most of the work on opinion dynamics models focuses on the case of two or three opinion types. We consider the case of an arbitrary number of opinions in the mean field case of the naming game model in which it is assumed the population is infinite and all individuals are neighbors. A particular challenge of the naming game model is that the number of variables, which corresponds to the number of possible sets of opinions, grows exponentially with the number of possible opinions. We present a method for generating mean field dynamical equations for the general case of k opinions. We calculate the steady states in two important special cases in arbitrarily high dimension: the case in which there exist zealots of only one type, and the case in which there are an equal number of zealots for each opinion. We show that in these special cases a phase transition occurs at critical values p(c) of the parameter p describing the fraction of zealots. In the former case, the critical value determines the threshold value beyond which it is not possible for the opinion with no zealots to be held by more nodes than the opinion with zealots, and this point remains fixed regardless of dimension. In the latter case, the critical point p(c) is the threshold value beyond which a stalemate between all k opinions is guaranteed, and we show that it decays precisely as a lognormal curve in k.