Fibroblast Growth Factor-9 Enhances M2 Macrophage Differentiation and Attenuates Adverse Cardiac Remodeling in the Infarcted Diabetic Heart

Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean +/- SEM; MI: 2.02% +/- 0.23% vs. Sham 0.75% +/- 0.07%; p \u3c 0.05) and associated pro-inflammatory cytokines (TNF-alpha, MCP-1, and IL-6), adverse cardiac remodeling (Mean +/- SEM; MI: 33% +/- 3.04% vs. Sham 2.2% +/- 0.33%; p \u3c 0.05), and left ventricular dysfunction (Mean +/- SEM; MI: 35.4% +/- 1.25% vs. Sham 49.19% +/- 1.07%; p \u3c 0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean +/- SEM; MI+FGF-9: 1.39% +/- 0.1% vs. MI: 2.02% +/- 0.23%; p \u3c 0.05), increased M2 macrophage differentiation (Mean +/- SEM; MI+FGF-9: 4.82% +/- 0.86% vs. MI: 0.85% +/- 0.3%; p \u3c 0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean +/- SEM; MI+FGF-9: 11.59% +/- 1.2% vs. MI: 33% +/- 3.04%; p \u3c 0.05), and improved cardiac function (Fractional shortening, Mean +/- SEM; MI+FGF-9: 41.51% +/- 1.68% vs. MI: 35.4% +/- 1.25%; p \u3c 0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to mediate monocyte to M2 differentiation and confer cardiac protection in the post-MI diabetic heart

Nonlinear dynamics of the interface of dielectric liquids in a strong electric field: Reduced equations of motion

The evolution of the interface between two ideal dielectric liquids in a strong vertical electric field is studied. It is found that a particular flow regime, for which the velocity potential and the electric field potential are linearly dependent functions, is possible if the ratio of the permittivities of liquids is inversely proportional to the ratio of their densities. The corresponding reduced equations for interface motion are derived. In the limit of small density ratio, these equations coincide with the well-known equations describing the Laplacian growth.Comment: 10 page

Drug utilization study in diabetic patients seeking medical treatment in a north Indian rural medical college hospital

Background: Diabetes Mellitus is a chronic disease and its life-long management causes burden on lifestyle and financial condition of the patients. Drug utilization studies provide useful insights into the current prescribing practices.Methods: To evaluate the drug utilization pattern of anti-diabetic drugs in diabetic patients. A prospective observational study was carried out in adult diabetic patients visiting the Wards and Outpatient Department of General Medicine of a tertiary care hospital. The demographic data and utilization of different classes of anti-diabetic agents as well as individual drugs were analyzed.Results: In 125 patients (Male-65, Female-60), a total of 379 drugs (average 3.032±2.05) were used per day, out of which 76 (20.05%) were rational fixed dose combinations (FDCs) and 261 (68.86%) were prescribed from National List of Essential Medicines (NLEM) 2015. The number of drugs prescribed to be ingested was 326 (86.01%) and 63 (16.62%) were injectables.Conclusions: It was found that the prescription tendencies of the doctors were quite rational. More improvement can be done by sensitizing them to prescribe more drugs from NLEM. The limitations in the affordability of rural population should be taken care of while prescribing drugs for this chronic disease

Development of Some Larval Nematodes in Experimental and Natural Animal Hosts: An Insight into Development of Pathological Lesions vis-a-vis Host-Parasite Interactions

Infective third-stage larvae of three spiruroid nematodes, Ascarops strongylina and Physocephalus sexalatus of pigs and Spirocerca lupi of dogs, were recovered from 14 species of coprophagous beetles belonging to 4 different genera. These larvae were fed to rabbits and/or guinea pigs to study their development in these experimental hosts. Larvae of A. strongylina reached the adult stage in all rabbits and one guinea pig. The adult worms recovered in these hosts were 40% and 4%, respectively, and became diminutive in comparison to their natural hosts. The larvae of P. sexalatus became reencysted in the gastric wall of rabbits inducing marked pathological changes. The infective larvae of S. lupi became reencapsulated in the stomach wall of the rabbit and also showed development in the aortic wall. Adults of Toxocara canis of dog, collected from 5 different regions of the Indian subcontinent, varied significantly in size. The mouse passage of infective larvae of one of these types led to the recovery of the adults from the experimental dogs that were smaller in size and caused severe pathology in natural experimental hosts. Developmental effects shown in experimental hosts and host specificity are of value in understanding the evolution of nematode parasitism

Regulation of PTEN/Akt Pathway Enhances Cardiomyogenesis and Attenuates Adverse Left Ventricular Remodeling following Thymosin beta 4 Overexpressing Embryonic Stem Cell Transplantation in the Infarcted Heart

Thymosin beta 4 (T beta 4), a small G-actin sequestering peptide, mediates cell proliferation, migration, and angiogenesis. Whether embryonic stem (ES) cells, overexpressing T beta 4, readily differentiate into cardiac myocytes in vitro and in vivo and enhance cardioprotection following transplantation post myocardial infarction (MI) remains unknown. Accordingly, we established stable mouse ES cell lines, RFP-ESCs and T beta 4-ESCs, expressing RFP and an RFP-T beta 4 fusion protein, respectively. In vitro, the number of spontaneously beating embryoid bodies (EBs) was significantly increased in T beta 4-ESCs at day 9, 12 and 15, compared with RFP-ESCs. Enhanced expression of cardiac transcriptional factors GATA-4, Mef2c and Txb6 in T beta 4-EBs, as confirmed with real time-PCR analysis, was accompanied by the increased number of EB areas stained positive for sarcomeric alpha-actin in T beta 4-EBs, compared with the RFP control, suggesting a significant increase in functional cardiac myocytes. Furthermore, we transplanted T beta 4-ESCs into the infarcted mouse heart and performed morphological and functional analysis 2 weeks after MI. There was a significant increase in newly formed cardiac myocytes associated with the Notch pathway, a decrease in apoptotic nuclei mediated by an increase in Akt and a decrease in levels of PTEN. Cardiac fibrosis was significantly reduced, and left ventricular function was significantly augmented in the T beta 4-ESC transplanted group, compared with controls. It is concluded that genetically modified T beta 4-ESCs, potentiates their ability to turn into cardiac myocytes in vitro as well as in vivo. Moreover, we also demonstrate that there was a significant decrease in both cardiac apoptosis and fibrosis, thus improving cardiac function in the infarcted heart

Extreme timescale core-level spectroscopy with tailored XUV pulses

A new approach for few-femtosecond time-resolved photoelectron spectroscopy in condensed matter that balances the combined needs for both temporal and energy resolution is demonstrated. Here, the method is designed to investigate a prototypical Mott insulator, tantalum disulphide (1T-TaS2), which transforms from its charge-density-wave ordered Mott insulating state to a conducting state in a matter of femtoseconds. The signature to be observed through the phase transition is a charge-density-wave induced splitting of the Ta 4f core-levels, which can be resolved with sub-eV spectral resolution. Combining this spectral resolution with few-femtosecond time resolution enables the collapse of the charge ordered Mott state to be clocked. Precise knowledge of the sub-20-femtosecond dynamics will provide new insight into the physical mechanism behind the collapse and may reveal Mott physics on the timescale of electronic hopping.Comment: 20 pages, 6 figure

Structural Color Production in Melanin-based Disordered Colloidal Nanoparticle Assemblies in Spherical Confinement

Melanin is a ubiquitous natural pigment that exhibits broadband absorption and high refractive index. Despite its widespread use in structural color production, how the absorbing material, melanin, affects the generated color is unknown. Using a combined molecular dynamics and finite-difference time-domain computational approach, this paper investigates structural color generation in one-component melanin nanoparticle-based supra-assemblies (called supraballs) as well as binary mixtures of melanin and silica (non-absorbing) nanoparticle-based supraballs. Experimentally produced one-component melanin and one-component silica supraballs, with thoroughly characterized primary particle characteristics using neutron scattering, produce reflectance profiles similar to the computational analogues, confirming that the computational approach correctly simulates both absorption and multiple scattering from the self-assembled nanoparticles. These combined approaches demonstrate that melanin's broadband absorption increases the primary reflectance peak wavelength, increases saturation, and decreases lightness factor. In addition, the dispersity of nanoparticle size more strongly influences the optical properties of supraballs than packing fraction, as evidenced by production of a larger range of colors when size dispersity is varied versus packing fraction. For binary melanin and silica supraballs, the chemistry-based stratification allows for more diverse color generation and finer saturation tuning than does the degree of mixing/demixing between the two chemistries.Comment: 40 pages, Figure

Modeling Structural Colors from Disordered One-Component Colloidal Nanoparticle-based Supraballs using Combined Experimental and Simulation Techniques

Bright, saturated structural colors in birds have inspired synthesis of self-assembled, disordered arrays of assembled nanoparticles with varied particle spacings and refractive indices. However, predicting colors of assembled nanoparticles, and thereby guiding their synthesis, remains challenging due to the effects of multiple scattering and strong absorption. Here, we use a computational approach to first reconstruct the nanoparticles' assembled structures from small-angle scattering measurements and then input the reconstructed structures to a finite-difference time-domain method to predict their color and reflectance. This computational approach is successfully validated by comparing its predictions against experimentally measured reflectance and provides a pathway for reverse engineering colloidal assemblies with desired optical and photothermal properties.Comment: 14 pages, 3 figures, 1 ToC figur

Mechanism of Structural Colors in Binary Mixtures of Nanoparticle-based Supraballs

Inspired by structural colors in avian species, various synthetic strategies have been developed to produce non-iridescent, saturated colors using nanoparticle assemblies. Mixtures of nanoparticles varying in particle chemistry (or complex refractive indices) and particle size have additional emergent properties that impact the color produced. For such complex multi-component systems, an understanding of assembled structure along with a robust optical modeling tool can empower scientists to perform intensive structure-color relationship studies and fabricate designer materials with tailored color. Here, we demonstrate how we can reconstruct the assembled structure from small-angle scattering measurements using the computational reverse-engineering analysis for scattering experiments (CREASE) method and then use the reconstructed structure in finite-difference time-domain (FDTD) calculations to predict color. We successfully, quantitatively predict experimentally observed color in mixtures containing strongly absorbing melanin nanoparticles and demonstrate the influence of a single layer of segregated nanoparticles on color produced. The versatile computational approach presented in this work is useful for engineering synthetic materials with desired colors without laborious trial and error experiments.Comment: 23 Pages, 5 Figures, 1 ToC Figur