75 research outputs found

    Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

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    Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease

    S‌E‌N‌S‌I‌T‌I‌V‌I‌T‌Y A‌N‌A‌L‌Y‌S‌I‌S O‌N T‌H‌E E‌F‌F‌E‌C‌T‌I‌V‌E P‌A‌R‌A‌M‌E‌T‌E‌R‌S O‌F G‌R‌O‌U‌N‌D D‌E‌F‌O‌R‌M‌A‌T‌I‌O‌N V‌A‌L‌U‌E B‌Y M‌I‌C‌R‌O T‌U‌N‌N‌E‌L‌I‌N‌G M‌E‌T‌H‌O‌D W‌H‌I‌L‌E P‌I‌P‌E J‌A‌C‌K‌I‌N‌G O‌P‌E‌R‌A‌T‌E‌S

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    I‌n r‌e‌c‌e‌n‌t y‌e‌a‌r‌s, m‌i‌c‌r‌o t‌u‌n‌n‌e‌l‌i‌n‌g m‌e‌t‌h‌o‌d h‌a‌s b‌e‌e‌n d‌e‌v‌e‌l‌o‌p‌e‌d q‌u‌i‌c‌k‌l‌y i‌n c‌o‌m‌p‌a‌r‌i‌s‌o‌n t‌o o‌t‌h‌e‌r o‌p‌e‌n e‌x‌c‌a‌v‌a‌t‌i‌o‌n m‌e‌t‌h‌o‌d‌s. M‌i‌c‌r‌o t‌u‌n‌n‌e‌l‌i‌n‌g i‌s a m‌e‌t‌h‌o‌d f‌o‌r i‌n‌s‌t‌a‌l‌l‌i‌n‌g t‌h‌e p‌i‌p‌e‌l‌i‌n‌e‌s, c‌h‌a‌n‌n‌e‌l‌s a‌n‌d u‌n‌d‌e‌r‌g‌r‌o‌u‌n‌d c‌o‌n‌d‌u‌i‌t‌s.I‌n r‌e‌c‌e‌n‌t y‌e‌a‌r‌s, m‌i‌c‌r‌o t‌u‌n‌n‌e‌l‌i‌n‌g m‌e‌t‌h‌o‌d h‌a‌s b‌e‌e‌n d‌e‌v‌e‌l‌o‌p‌e‌d q‌u‌i‌c‌k‌l‌y c‌o‌m‌p‌a‌r‌e‌d t‌o o‌t‌h‌e‌r o‌p‌e‌n e‌x‌c‌a‌v‌a‌t‌i‌o‌n m‌e‌t‌h‌o‌d‌s. I‌n t‌h‌i‌s m‌e‌t‌h‌o‌d, h‌y‌d‌r‌a‌u‌l‌i‌c j‌a‌c‌k‌s a‌r‌e u‌s‌e‌d f‌o‌r p‌i‌p‌e d‌r‌i‌v‌i‌n‌g w‌i‌t‌h a s‌p‌e‌c‌i‌a‌l d‌e‌s‌i‌g‌n. T‌h‌e p‌i‌p‌e‌s a‌r‌e p‌l‌a‌c‌e‌d b‌e‌h‌i‌n‌d t‌h‌e e‌x‌c‌a‌v‌a‌t‌i‌o‌n d‌r‌i‌l‌l, d‌r‌i‌v‌e‌n i‌n‌t‌o t‌h‌e g‌r‌o‌u‌n‌d a‌l‌o‌n‌g w‌i‌t‌h t‌h‌e g‌r‌o‌u‌n‌d e‌x‌c‌a‌v‌a‌t‌i‌o‌n s‌i‌m‌u‌l‌t‌a‌n‌e‌o‌u‌s‌l‌y. T‌h‌e r‌e‌s‌u‌l‌t o‌f t‌h‌i‌s m‌e‌t‌h‌o‌d i‌s a f‌l‌e‌x‌i‌b‌l‌e, i‌m‌p‌e‌r‌m‌e‌a‌b‌l‌e a‌n‌d r‌e‌s‌i‌s‌t‌a‌n‌t s‌t‌r‌u‌c‌t‌u‌r‌e c‌o‌n‌s‌t‌r‌u‌c‌t‌i‌o‌n p‌i‌p‌e‌l‌i‌n‌e‌s. T‌h‌e m‌i‌c‌r‌o t‌u‌n‌n‌e‌l‌i‌n‌g m‌e‌t‌h‌o‌d r‌e‌d‌u‌c‌e‌s t‌h‌e r‌e‌q‌u‌i‌r‌e‌m‌e‌n‌t n‌u‌m‌b‌e‌r o‌f t‌r‌a‌n‌s‌p‌o‌r‌t‌i‌n‌g m‌a‌t‌e‌r‌i‌a‌l‌s f‌o‌r o‌p‌e‌r‌a‌t‌i‌o‌n a‌c‌t‌i‌v‌i‌t‌i‌e‌s a‌n‌d t‌h‌e m‌a‌c‌h‌i‌n‌e‌s t‌r‌a‌f‌f‌i‌c a‌n‌d d‌e‌v‌i‌c‌e‌s. T‌o‌o A‌s a r‌e‌s‌u‌l‌t, i‌t‌s e‌v‌e‌n‌t‌s a‌r‌e r‌e‌d‌u‌c‌e‌d. A‌c‌c‌o‌r‌d‌i‌n‌g t‌o t‌h‌i‌s m‌e‌t‌h‌o‌d, a‌l‌m‌o‌s‌t a‌l‌l t‌h‌e a‌c‌t‌i‌v‌i‌t‌i‌e‌s a‌r‌e p‌e‌r‌f‌o‌r‌m‌e‌d u‌n‌d‌e‌r‌g‌r‌o‌u‌n‌d. H‌e‌n‌c‌e, t‌h‌e n‌e‌g‌l‌i‌g‌i‌b‌l‌e i‌n‌t‌e‌r‌f‌e‌r‌e‌n‌c‌e‌s a‌r‌e o‌c‌c‌u‌r‌r‌e‌d w‌i‌t‌h e‌n‌v‌i‌r‌o‌n‌m‌e‌n‌t. T‌h‌u‌s, t‌h‌e a‌m‌o‌u‌n‌t o‌f e‌n‌v‌i‌r‌o‌n‌m‌e‌n‌t‌a‌l d‌e‌t‌e‌r‌i‌o‌r‌a‌t‌i‌o‌n i‌s v‌e‌r‌y l‌o‌w. I‌n s‌o‌m‌e c‌a‌s‌e‌s, p‌e‌r‌f‌o‌r‌m‌i‌n‌g t‌h‌e o‌p‌e‌r‌a‌t‌i‌o‌n, i‌n‌c‌r‌e‌a‌s‌e‌s t‌h‌e n‌e‌g‌a‌t‌i‌v‌e e‌f‌f‌e‌c‌t‌s o‌f v‌i‌b‌r‌a‌t‌i‌o‌n‌s f‌r‌o‌m p‌i‌p‌e d‌r‌i‌v‌i‌n‌g a‌n‌d c‌a‌u‌s‌e‌s t‌h‌e p‌r‌o‌b‌l‌e‌m‌s s‌u‌c‌h a‌s s‌e‌t‌t‌l‌e‌m‌e‌n‌t‌s o‌r s‌w‌e‌l‌l‌i‌n‌g (h‌e‌a‌v‌i‌n‌g) o‌f t‌h‌e g‌r‌o‌u‌n‌d s‌u‌r‌f‌a‌c‌e. U‌p‌o‌n a‌n‌a‌l‌y‌s‌i‌s, s‌o‌m‌e p‌a‌r‌a‌m‌e‌t‌e‌r‌s h‌a‌v‌e m‌o‌r‌e i‌n‌f‌l‌u‌e‌n‌c‌e‌s r‌a‌t‌h‌e‌r t‌h‌a‌n o‌t‌h‌e‌r‌s, a‌n‌d s‌o‌m‌e o‌f t‌h‌e‌m c‌o‌u‌l‌d b‌e i‌g‌n‌o‌r‌e‌d d‌u‌e t‌o l‌o‌w i‌m‌p‌o‌r‌t‌a‌n‌c‌e i‌n t‌h‌e m‌o‌d‌e‌l. T‌h‌e‌r‌e‌f‌o‌r‌e, i‌n‌v‌e‌s‌t‌i‌g‌a‌t‌i‌n‌g t‌h‌e e‌f‌f‌e‌c‌t o‌f v‌a‌r‌i‌o‌u‌s i‌n‌d‌e‌p‌e‌n‌d‌e‌n‌t p‌a‌r‌a‌m‌e‌t‌e‌r‌s i‌s i‌m‌p‌o‌r‌t‌a‌n‌t, i.e. s‌e‌n‌s‌i‌t‌i‌v‌e a‌n‌a‌l‌y‌s‌i‌s. T‌h‌e a‌i‌m o‌f t‌h‌i‌s s‌t‌u‌d‌y i‌s t‌o c‌o‌m‌p‌a‌r‌e t‌h‌e a‌c‌t‌u‌a‌l d‌e‌f‌o‌r‌m‌a‌t‌i‌o‌n‌s o‌c‌c‌u‌r‌r‌e‌d i‌n g‌r‌o‌u‌n‌d s‌u‌r‌f‌a‌c‌e d‌u‌e t‌o b‌e‌h‌a‌v‌i‌o‌r s‌u‌r‌v‌e‌y w‌i‌t‌h t‌h‌e v‌a‌l‌u‌e‌s o‌f n‌u‌m‌e‌r‌i‌c‌a‌l m‌o‌d‌e‌l‌i‌n‌g. I‌n a‌d‌d‌i‌t‌i‌o‌n, t‌h‌i‌s s‌t‌u‌d‌y a‌i‌m‌s t‌o i‌n‌v‌e‌s‌t‌i‌g‌a‌t‌e t‌h‌e e‌f‌f‌e‌c‌t o‌f v‌a‌r‌i‌o‌u‌s p‌a‌r‌a‌m‌e‌t‌e‌r‌s o‌n s‌o‌i‌l s‌e‌t‌t‌l‌e‌m‌e‌n‌t v‌a‌l‌u‌e‌s

    Colon Lipoma: a Case Report and Review of the Literature

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    ABSTRACT Colon lipomas are rare.They are almost always asymptomatic;only when their diameter is more than 3 cm do they become symptomatic.They tend to occur in an older population and most of the cases are located at the right side of the large bowel. Usually the diagnosis is not made until operation is performed.We describe a 67-year-old woman with a large colonic submucosal lipoma causing left-sided abdominal pain and altered bowel habit.Abdominal sonography,CT scan and colonoscopy showed a mass 5 c

    Colon Lipoma: A Case Report And Review Of The Literature

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    Colon lipomas are rare. They are almost always asymptomatic; only when their diameter is more than 3 cm do they become symptomatic. They tend to occur in an older population and most of the cases are located at the right side of the large bowel. Usually the diagnosis is not made until operation is performed. We describe a 67-year-old woman with a large colonic submucosal lipoma causing left-sided abdominal pain and altered bowel habit. Abdominal sonography, CT scan and colonoscopy showed a mass 5 cm x 4.5cm x 4 cm located 90cm from the anal verge. Left hemicolectomy was performed, and histologic examination revealed the mass to be a benign colonic lipoma. We also reviewed the literature on the subject to examine the main characteristics of lipoma of the colon

    Application of Impregnated Almond Shell Activated Carbon by Zinc and Zinc Sulfate for Nitrate Removal from Water

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    In this study impregnated almond shell activated carbon by Zn° and ZnSO4 were used as adsorbent with a particle size of 10-20 mesh. The objective of this research was to determine the ability of impregnated activated carbon in nitrate removal. The modified activated carbon had 1mm effective size, with a uniformity coefficient of 1.18. Potassium nitrate solution was used in batch adsorption experiments for nitrate removal from water. The effects of nitrate concentration, activated carbon dosage and time of contact were studied. Experimental data showed that modified activated carbon by Zn° and ZnSO4 was more effective than virgin almond activated carbon for nitrate removal. The maximum nitrate removal was 64%-80% and 5%-42% for modified activated carbon and virgin activated carbon, respectively. While virgin activated carbon used, nitrate-N decreased from 20 to 15mg/L in 30min reaction. The final nitrate concentration was not in the standard range of WHO recommendations for water quality; while impregnated activated carbons were used, nitrate drcreased to <10mg/L. Maximum removal was over 16-17mg nitrate-N per 1g activated carbon for impregnated activated carbon. The experiments were conducted at pH=6.2, 20ºC and initial concentrations of 20mg/L nitrate-N. Increase in modified activated carbon dosage increased the nitrate removal efficiency. The equilibrium time was found to be 45min for modified activated carbon

    Design of a Micro-Probe For Direct Measurement of Convection Heat Transfer on a Vertical

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    A proximity probe with two k-type thermocouples, 1.5 mm apart, was designed, built to simultaneously measure local surface and air temperatures on the PV and to quantify local convention heat transfer coefficient. Experimental investigations of natural convection on a vertical photovoltaic (PV) panel exposed to solar radiations are presented. The variation of non-isothermal surface temperature of a PV is expressed with a second-order polynomial relation. In the absence of any correlation to predict the natural convection heat transfer coefficient on a PV, experimental results are presented in the form of variations of the local Nusselt numbers (Nuz), and the average Nusselt numbers (Nu), with Rayleigh number (Ra). The variations are best expressed with a power law correlation form of Nu=a*(Ra)^b for the range 10^6 <Ra<10^8 where a and b are determined experimentally. The power-law correlations for photovoltaic were compared with a number of correlations developed from natural convection research in laboratories. The analysis showed that for a given Rayleigh number, the predicted value of Nusselt number by the PV correlations are within the range covered by others. However, the PV correlations overestimate the Nusselt number by 20% in Rayleigh number higher than 10^6 . The work is in progress to further extend the correlation to predict the combined radiation and convection on all PV configurations, as required in the efficient design of building integrated photovoltaic (BIPV) systems

    Exogenous potassium phosphite application improved PR-protein expression and associated physio-biochemical events in cucumber challenged by Pseudoperonospora cubensis

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    In the present study, the effect of potassium phosphite on Pseudoperonospora cubensis-inoculated cucumber plants was investigated. Different defense-related enzymes including laccase, polyphenoloxidase and glucanase as well as total protein and lignin contents were analyzed. Anatomical alterations in plant tissues were analyzed using a light microscope. Expression changes in major pathogenesis-related genes were studied at different time courses. The highest expression of glucanase was observed in pre-inoculated plants (97 higher than control) at 24 h with 97 increase compared to the control plants, while Chitinase transcripts were accumulated at a maximum level in potassium phosphite-treated plants 96 h after inoculation with 93 increase over control plants. Analysis of polygalacturonase inhibitor proteins gene expression revealed a transcription peak (96 increase over control plants) 48 h after inoculation. The potassium phosphite-treated plants exhibited an increase in β-1,3-glucanase (82) enzymatic activity as well as total protein (53), polyphenoloxidase (21), laccase (11) and lignin contents (15) in comparison to the control. The results of the anatomical assay showed an increase in the vascular bundle diameter in potassium phosphite-treated plants (174 μm) and a decrease in pathogen-treated leaves (66 μm) compared with the control (100 μm). It can be suggested that potassium phosphite treatment induced higher expression of plant defense genes and increased laccase and polyphenoloxidase activities which in turn enhanced lignin deposition in plant tissues. The findings of the present study would be implemented for designing a controlling program to decrease the adverse effect of Pseudoperonospora cubensis on cucumber plants. © 2018 Elsevier B.V

    Exogenous potassium phosphite application improved PR-protein expression and associated physio-biochemical events in cucumber challenged by Pseudoperonospora cubensis

    No full text
    In the present study, the effect of potassium phosphite on Pseudoperonospora cubensis-inoculated cucumber plants was investigated. Different defense-related enzymes including laccase, polyphenoloxidase and glucanase as well as total protein and lignin contents were analyzed. Anatomical alterations in plant tissues were analyzed using a light microscope. Expression changes in major pathogenesis-related genes were studied at different time courses. The highest expression of glucanase was observed in pre-inoculated plants (97 higher than control) at 24 h with 97 increase compared to the control plants, while Chitinase transcripts were accumulated at a maximum level in potassium phosphite-treated plants 96 h after inoculation with 93 increase over control plants. Analysis of polygalacturonase inhibitor proteins gene expression revealed a transcription peak (96 increase over control plants) 48 h after inoculation. The potassium phosphite-treated plants exhibited an increase in β-1,3-glucanase (82) enzymatic activity as well as total protein (53), polyphenoloxidase (21), laccase (11) and lignin contents (15) in comparison to the control. The results of the anatomical assay showed an increase in the vascular bundle diameter in potassium phosphite-treated plants (174 μm) and a decrease in pathogen-treated leaves (66 μm) compared with the control (100 μm). It can be suggested that potassium phosphite treatment induced higher expression of plant defense genes and increased laccase and polyphenoloxidase activities which in turn enhanced lignin deposition in plant tissues. The findings of the present study would be implemented for designing a controlling program to decrease the adverse effect of Pseudoperonospora cubensis on cucumber plants. © 2018 Elsevier B.V

    Isolation And Characterization Of A Novel Denitrifying Bacterium With High Nitrate Removal: Pseudomonas Stutzeri

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    The aim of this study was to isolate and characterize a high efficiency denitrifier bacterium for reducing nitrate in wastewater. Six denitrifier bacteria with nitrate removal activities were isolated from a petrochemical industry effluent with high salinity and high nitrogen concentrations without treatment. The isolated bacteria were tested for nitrate reomoval activity. One of the bacterium displayed the highest reduction of nitrate. The strain was preliminarily identified using biochemical tests and further identified based on similarity of PCR-16S rRNA using universal primers. Biochemical and molecular experiments showed that the best bacterium with high nitrate removal potential was Pseudomonas stutzeri, a member of the α subclass of the class Proteobacteria. The extent of nitrate removal efficiency was 99% at 200 mg/L NO3 and the nitrite content of the effluent was in the prescribed limit. The experiments showed the ability of Pseudomonas stutzeri to rapidly remove nitrate under anoxic conditions. The strain showed to be potentially good candidate for biodenitrification of high nitrate solutions
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