622 research outputs found

    Adatom controlled emergence of high hardness in biocompatible beta-Ti3Au intermetallic thin film surfaces

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    There is growing international interest in hard biocompatible thin film surface coatings to extend the lifetime of medical implants. Parameters of the physical vapour deposition technique can be utilized to fine tune the microstructure and resulting properties of the growing thin film surface by modifying the adatom mobility of the incoming species. This work investigates the evolution of high hardness and biocompatibility of sputter deposited beta-Ti3Au intermetallic thin film surfaces as a function of growth temperature and pressure. Titanium and gold are sputtered in an optimised 3:1 ratio over glass and Ti6Al4V substrates at varying pressures of 0.3 to 1.2 Pa and temperatures of 25 to 450°C. The microstructure and crystallinity of the deposited films improved with reduction in pressure from 1.2 to 0.3 Pa but development of the ÎČ-Ti3Au intermetallic compound occurred at temperatures above 350˚C. The density of the films also increased with reducing pressure, whereas improvement in their columnar structure was observed with increasing substrate temperature. These microstructural changes caused by adatom mobility variation, led to the emergence of superior mechanical surface hardness, reaching a peak value of 12.5 GPa for films grown at 0.3 Pa and 450°C. All thin film surfaces were highly biocompatible with ion leaching levels below 1 ppm, and films deposited at lower pressure exhibited much safer cytotoxic profiles against L929 mouse fibroblasts. This work demonstrates the emergence of high hardness and biocompatibility in Ti3Au thin film surfaces with potential as next generation medical implant coating materials

    Iridium(iii) complexes of 1,2,4-triazines as potential bioorthogonal reagents: metal coordination facilitates luminogenic reaction with strained cyclooctynes

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    In this paper we describe unprecedented Ir(III) complexes of 5-(2-pyridyl)-1,2,4-triazine and their reactivity towards the strained cyclooctyne BCN. The coordination of a 1,2,4-triazine ring to an iridium(III) ion drastically increases the speed of the reaction, showing the second order rate constant of 8 M−1 s−1, the record value to date for a triazine-BCN reaction

    Novel Docosahexaenoic Acid Ester of Phloridzin Inhibits Proliferation and Triggers Apoptosis in an In Vitro Model of Skin Cancer

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    Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability assays. However, growth inhibition and induction of both apoptosis and necrosis was more evident in melanoma (A375) and epidermoid carcinoma (A431) cells, whereas non-tumorigenic keratinocytes (HaCaT) appeared to be more resistant as detected by flow cytometry. More specifically, PZDHA-induced cell cycle growth arrest at the G2/M phase in A375 and A431 cells in contrast to HaCaT cells, which were growth arrested at the G0/G1 phase. Elevated intracellular generation of reactive oxygen species ROS was detected in all cell lines. Overall, our findings support the potential of PZDHA as a novel therapeutic means against human skin cancer

    Metabolic Disorder Dysfunction in Parkinson’s Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism

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    The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson’s disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism

    Mechanical performance of biocompatible Ti-Au thin films grown on glass and Ti6Al4V substrates

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    Ti-Au intermetallic based material systems are being extensively studied to develop hard and wear resistant biocompatible thin film coatings over implant devices to extend their lifetime 1, 2. However, the measurement of these mechanical characteristics depends upon factors such as surface properties of the substrates and their temperature during thin film deposition. In this work, Ti-Au thin films were deposited by magnetron sputtering on both glass and Ti6Al4V substrates at two different temperatures. These films were studied for their mechanical properties by the nanoindentation technique in both load control and displacement control modes using a Berkovich tip. XRD patterns and cross section SEM images detail the microstructure while AFM images present the surface morphology of these Ti-Au thin films. Biocompatibility of the films is verified by cytotoxicity tests on L929 mouse fibroblast cells using Alamar blue reagent and the ions leaching in the film extracts is measured using the ICPOEMS technique. Standard deviation for hardness of films on glass substrates is ~4 times lower than that on Ti6Al4V substrates and is corelated to a corresponding increase in surface roughness from 2nm for glass to 40nm for Ti6Al4V substrates 3. Increasing substrate temperature leads to an increase in film hardness from 5.1 to 8.9GPa and is related to the development of a super hard ÎČ phase of the Ti3Au intermetallic. The standard deviation of this peak mechanical hardness value of 8.9GPa is reduced by 3 times when measured in displacement control mode compared to the value measured in load control mode due of the effect of nanoindentation tip penetration depth. All the Ti-Au thin films exhibit excellent cytotoxicity values above 95% and ion leaching below 100ppb. This work presents a comparative study to optimize hardness measurement of Ti-Au thin films, critical for a better understanding of these super hard biocompatible coatings

    Polyphenolics, glucosinolates and isothiocyanates profiling of aerial parts of \u3ci\u3eNasturtium officinale\u3c/i\u3e (Watercress)

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    Watercress (Nasturtium officinale) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that watercress contains significantly higher levels of gluconasturtiin, phenethyl isothiocyanate, quercetin-3-O-rutinoside and isorhamnetin, among others, with their content decreasing from flowers (82.11 ± 0.63, 273.89 ± 0.88, 1459.30 ± 12.95 and 289.40 ± 1.37 ng/g of dry extract respectively) to leaves (32.25 ± 0.74, 125.02 ± 0.52, 1197.86 ± 4.24 and 196.47 ± 3.65 ng/g of det extract respectively) to stems (9.20 ± 0.11, 64.7 ± 0.9, 41.02 ± 0.18, 65.67 ± 0.84 ng/g of dry extract respectivbely). Pearson’s correlation analysis has shown that the content of isothiocyanates doesn’t depend only on the bioconversion of individual glucosinolates but also on other glucosinolates of the same group. Overall, we have provided comprehensive analytical data of the major watercress metabolites thereby providing an opportunity to exploit different parts of watercress for potential therapeutic applications

    Stbd1-deficient mice display insulin resistance associated with enhanced hepatic ER-mitochondria contact

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    Starch binding domain-containing protein 1 (STBD1) is an endoplasmic reticulum (ER)-resident, glycogen-binding protein. In addition to glycogen, STBD1 has been shown to interact with several proteins implicated in glycogen synthesis and degradation, yet its function in glycogen metabolism remains largely unknown. In addition to the bulk of the ER, STBD1 has been reported to localize at regions of physical contact between mitochondria and the ER, known as Mitochondria-ER Contact sites (MERCs). Given the emerging correlation between distortions in the integrity of hepatic MERCs and insulin resistance, our study aimed to delineate the role of STBD1 in vivo by addressing potential abnormalities in glucose metabolism and ER-mitochondria communication associated with insulin resistance in mice with targeted inactivation of Stbd1 (Stbd1KO). We show that Stbd1KO mice at the age of 24 weeks displayed reduced hepatic glycogen content and aberrant control of glucose homeostasis, compatible with insulin resistance. In line with the above, Stbd1-deficient mice presented with increased fasting blood glucose and insulin levels, attenuated activation of insulin signaling in the liver and skeletal muscle and elevated liver sphingomyelin content, in the absence of hepatic steatosis. Furthermore, Stbd1KO mice were found to exhibit enhanced ER-mitochondria association and increased mitochondrial fragmentation in the liver. Nevertheless, the enzymatic activity of hepatic respiratory chain complexes and ER stress levels in the liver were not altered. Our findings identify a novel important role for STBD1 in the control of glucose metabolism, associated with the integrity of hepatic MERCs
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