11 research outputs found

    Smooth Muscle Stiffness Sensitivity is Driven by Soluble and Insoluble ECM Chemistry

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    Smooth muscle cell (SMC) invasion into plaques and subsequent proliferation is a major factor in the progression of atherosclerosis. During disease progression, SMCs experience major changes in their microenvironment, such as what integrin-binding sites are exposed, the portfolio of soluble factors available, and the elasticity and modulus of the surrounding vessel wall. We have developed a hydrogel biomaterial platform to examine the combined effect of these changes on SMC phenotype. We were particularly interested in how the chemical microenvironment affected the ability of SMCs to sense and respond to modulus. To our surprise, we observed that integrin binding and soluble factors are major drivers of several critical SMC behaviors, such as motility, proliferation, invasion, and differentiation marker expres- sion, and these factors modulated the effect of stiffness on proliferation and migration. Overall, modulus only modestly affected behaviors other than proliferation, relative to integrin binding and soluble factors. Surprisingly, patho- logical behaviors (proliferation, motility) are not inversely related to SMC marker expression, in direct conflict with previous studies on substrates coupled with single extracel- lular matrix (ECM) proteins. A high-throughput bead-based ELISA approach and inhibitor studies revealed that differ- entiation marker expression is mediated chiefly via focal adhesion kinase (FAK) signaling, and we propose that integrin binding and FAK drive the transition from a migratory to a proliferative phenotype. We emphasize the importance of increasing the complexity of in vitro testing platforms to capture these subtleties in cell phenotypes and signaling, in order to better recapitulate important features of in vivo disease and elucidate potential context-dependent therapeutic targets

    Swelling and Dye-Adsorption Characteristics of an Amphoteric Superabsorbent Polymer

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    Amphoteric superabsorbent polymers (SAPs) based on the anionic monomer sodium acrylate (SA) and the cationic monomer [2-(methacryloyloxy)­ethyl]­trimethylammonium chloride (METAC) were synthesized by solution polymerization using <i>N</i>,<i>N</i>′-methylenebisacrylamide as a cross-linking agent. The ratio of anionic to cationic repeat units was varied to obtain anionic, cationic, and amphoteric SAPs. The synthesized SAPs were characterized by Fourier transform infrared spectroscopy. The equilibrium swelling capacity of the SAPs was found to be dependent on the nature and extent of the net charge on the SAPs but independent of pH. The equilibrium swelling capacity was lowest for the SAP whose ratio of anionic to cationic repeat units was unity. The equilibrium swelling capacity increased as this ratio deviated from unity. The adsorption of an anionic dye (orange G) and a cationic dye (methylene blue) was carried out from the individual solution as well as from their mixture. The adsorption of the dyes was found to be dependent on the nature and amount of net charge on the SAPs but independent of pH. The amount of the dye adsorbed decreased as the net charge on the amphoteric SAPs decreased. The amphoteric SAPs with net negative or positive charge selectively adsorbed oppositely charged dyes from the mixture, but the amounts adsorbed were lower than those adsorbed from the individual dye solutions

    Polyanhydrides of Castor Oil-Sebacic Acid for Controlled Release Applications

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    A family of high molecular weight castor oil (CO)-based biodegradable polyanhydrides was synthesized by a catalyst-free melt-condensation reaction between prepolymers of CO and sebacic acid (SA). The structure of the polymers was characterized by H-1 NMR and Fourier transform infrared spectroscopy, which indicated the formation of the anhydride bond along the polymer backbone. Thermal analysis and X-ray diffraction confirmed the semicrystalline nature of the polymers. Incorporation of SA enhanced the crystallinity of the polymer. The hydrophobic nature of these polymers was revealed by contact angle goniometry. Water wettability decreased with increase in SA content. Compressive tests demonstrated a sharp increase in strength and decrease in ductility with increasing SA content. In vitro hydrolytic degradation studies indicated surface-eroding behavior. The degradation rate decreased with an increase of SA content in the polymers because of increased crystallinity. The release studies of both hydrophobic and hydrophilic dyes followed zero-order kinetics. In vitro cell studies to assess the cytotoxicity of the polymer confirmed minimal toxicity of the degradation products. Thus, a family of CO-SA polyanhydrides have been synthesized and characterized for controlled release applications where the physical, mechanical, and degradation kinetics can be modulated by varying the weight fraction of the prepolymers

    Lef Congenital Mesoblasti Nephroma in a Term Male Neonate: A Case Report

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    Congenital mesoblasticnephroma (CMN) is a benign and very rare renal tumor, typically occurring in utero or during infancy. We are reporting a very young case of left sided classical congenital mesoblasticnephroma in a full term, small for gestational age, male neonate; who was detected with left sided flank mass immediately after birth. The patient was managed successfully by total nephrectomy. The diagnosis of CMN-classical type was confirmed on histopathological examination

    Polyanhydrides of Castor Oil–Sebacic Acid for Controlled Release Applications

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    A family of high molecular weight castor oil (CO)-based biodegradable polyanhydrides was synthesized by a catalyst-free melt–condensation reaction between prepolymers of CO and sebacic acid (SA). The structure of the polymers was characterized by <sup>1</sup>H NMR and Fourier transform infrared spectroscopy, which indicated the formation of the anhydride bond along the polymer backbone. Thermal analysis and X-ray diffraction confirmed the semicrystalline nature of the polymers. Incorporation of SA enhanced the crystallinity of the polymer. The hydrophobic nature of these polymers was revealed by contact angle goniometry. Water wettability decreased with increase in SA content. Compressive tests demonstrated a sharp increase in strength and decrease in ductility with increasing SA content. In vitro hydrolytic degradation studies indicated surface-eroding behavior. The degradation rate decreased with an increase of SA content in the polymers because of increased crystallinity. The release studies of both hydrophobic and hydrophilic dyes followed zero-order kinetics. In vitro cell studies to assess the cytotoxicity of the polymer confirmed minimal toxicity of the degradation products. Thus, a family of CO-SA polyanhydrides have been synthesized and characterized for controlled release applications where the physical, mechanical, and degradation kinetics can be modulated by varying the weight fraction of the prepolymers

    Antimicrobial Agents Based on Metal Complexes: Present Situation and Future Prospects

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    The rise in antimicrobial resistance is a cause of serious concern since the ages. Therefore, a dire need to explore new antimicrobial entities that can combat against the increasing threat of antibiotic resistance is realized. Studies have shown that the activity of the strongest antibiotics has reduced drastically against many microbes such as microfungi and bacteria (Gram-positive and Gram-negative). A ray of hope, however, was witnessed in early 1940s with the development of new drug discovery and use of metal complexes as antibiotics. Many new metal-based drugs were developed from the metal complexes which are potentially active against a number of ailments such as cancer, malaria, and neurodegenerative diseases. Therefore, this review is an attempt to describe the present scenario and future development of metal complexes as antibiotics against wide array of microbes
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