- Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity. [Journal Article]
- JBJACC Basic Transl Sci 2019; 4(3):304-317
- CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) confirmed interleukin (IL)-1β as an appealing therapeutic target for human atherosclerosis and related complications. However, there are…
CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) confirmed interleukin (IL)-1β as an appealing therapeutic target for human atherosclerosis and related complications. However, there are serious gaps in our understanding of IL-1 production in atherosclerosis. Herein the authors show that complex plaques, or plaques derived from patients with suboptimally controlled hyperlipidemia, or on no or low-intensity statin therapy, demonstrated higher recruitable IL-1β production. Generation of mature IL-1β was matched by IL-1α release, and both were attenuated by inhibition of NLR family pyrin domain containing 3 or caspase. These findings support the inflammasome as the main pathway for IL-1α/β generation in atherosclerosis and high-intensity lipid-lowering therapies as primary and additional anti-IL-1-directed therapies as secondary interventions in high-risk patients.
- Morin Hydrate Reverses Cisplatin Resistance by Impairing PARP1/HMGB1-Dependent Autophagy in Hepatocellular Carcinoma. [Journal Article]
- CCancers (Basel) 2019 Jul 15; 11(7)
- Chemoresistance is a major obstacle that limits the benefits of cisplatin-based chemotherapy in various cancers, including hepatocellular carcinoma. De-regulation of the poly(ADP-ribose) polymerase 1…
Chemoresistance is a major obstacle that limits the benefits of cisplatin-based chemotherapy in various cancers, including hepatocellular carcinoma. De-regulation of the poly(ADP-ribose) polymerase 1 (PARP1)/high-mobility group box 1 (HMGB1) signaling pathway has been proposed as an important mechanism involved in cisplatin-resistance. In this study, we investigated therapeutic potential of a natural flavonoid Morin hydrate against cisplatin-induced toxicity using the HepG2DR multi-drug resistant cell line, which is derived from the HepG2 human hepatocellular carcinoma cell line. HepG2DR cells were exposed to cisplatin and Morin hydrate alone or together after which autophagy and apoptotic signaling pathways were monitored by fluorometric assay and Western blot analysis. Xenograft mouse models were performed to confirm the in vitro effect of Morin hydrate. PARP1 was hyper activated in cisplatin-resistant HepG2DR cells. Cisplatin-induced PARP1 activation resulted in chemoresistance via increased autophagy. The cisplatin/Morin hydrate combination was effective in the reversal of the HepG2DR cell resistance via suppression of PARP1-mediated autophagy by regulating the HMGB1 and microtubule-associated protein 1A/1B light chain 3B (LC3) I/II. Moreover, PARP1 inhibition by 4-amino-1,8-naphthalimide or autophagy inhibition by a knockdown of the autophagy-related 5 (Atg5) gene resulted in sensitizing the HepG2DR cells to cisplatin (CP) through activation of the c-Jun N-terminal kinase (JNK) pathway. In a mouse xenograft model, the treatment of cisplatin with Morin hydrate reversed the increased expression of PARP and HMGB1 and significantly suppressed tumor growth. These findings indicate dysregulated expression of PARP1 confers cisplatin-resistance via autophagy activation in HepG2DR cells. Morin hydrate inhibits cisplatin-mediated autophagy induction, resulting in increased susceptibility of HepG2DR cells to cisplatin cytotoxicity. The combination of Morin hydrate with cisplatin may be a promising therapeutic strategy to enhance the efficacy of conventional chemotherapeutic drugs.
- A One-Pot Method for Removal of Thioacetyl Group via Desulfurization under Ultraviolet Light To Synthesize Deoxyglycosides. [Journal Article]
- OLOrg Lett 2019 Jul 16
- We herein developed an efficient method for removing thioacetyl to synthesize acylated deoxy glycosides in a one-pot reaction, where the thioacetyl was selectively deacetylated by hydrazine hydrate i…
We herein developed an efficient method for removing thioacetyl to synthesize acylated deoxy glycosides in a one-pot reaction, where the thioacetyl was selectively deacetylated by hydrazine hydrate in DMF within 2-5 min at room temperature, followed by desulfurization under UV light for 1-2 h in the presence of TCEP·HCl. The method was then used to synthesize 2-deoxy glycosides with absolute α/β-configuration via stereoselective control of C-2 thioacetate in glycosylation.
- Raman Signatures and Thermal Expansivity of Acetylene Clathrate Hydrate. [Journal Article]
- JPJ Phys Chem A 2019 Jul 16
- The vibrational signatures for the ν2 C≡C and ν1 symmetric C-H stretches of acetylene in cubic structure I clathrate, synthesized under ambient pressure, are reported for the first time. The most dia…
The vibrational signatures for the ν2 C≡C and ν1 symmetric C-H stretches of acetylene in cubic structure I clathrate, synthesized under ambient pressure, are reported for the first time. The most diagnostic features are at 1966 for ν2 and 3353 cm-1 for ν1, respectively, and are assigned to acetylene trapped in the large 51262 cages. In addition, the ν2 mode for acetylene occupying the small 512 cages are observed at 1972.5 cm-1, a red shift of 1.5 cm-1 from its gas phase frequency. Unit cell parameters and thermal expansion coefficients are determined via powder X-ray diffraction between 195 K and 225 K, and are found to be in good correlation with previous single crystal data at 143 K. The calculated density for acetylene clathrate is also reported, with values ranging from 0.985 g/cm3 at 195 K to 0.976 g/cm3 at 225 K. These results are relevant for spectral detection of acetylene-containing compounds on planetary bodies, as well as providing additional insights on the thermal behavior and physical properties of acetylene clathrate.
- Influence of Wood-Based Biomass Ash Admixing on the Structural, Mechanical, Hygric, and Thermal Properties of Air Lime Mortars. [Journal Article]
- MMaterials (Basel) 2019 Jul 10; 12(14)
- Mechanically-activated wood-based biomass ash (WBA) was studied as a potential active admixture for design of a novel lime-pozzolan-based mortar for renovation purposes. The replacement ratio of lime…
Mechanically-activated wood-based biomass ash (WBA) was studied as a potential active admixture for design of a novel lime-pozzolan-based mortar for renovation purposes. The replacement ratio of lime hydrate in a mortar mix composition was 5%, 10%, and 15% by mass. The water/binder ratio and the sand/binder ratio were kept constant for all examined mortar mixes. Both binder constituents were characterized by their powder density, specific density, BET (Brunauer-Emmett-Teller), and Blaine specific surfaces. Their chemical composition was measured by X-ray fluorescence analysis (XRF) and mineralogical analysis was performed using X-ray diffraction (XRD). Morphology of WBA was investigated by scanning electron microscopy (SEM) and element mapping was performed using an energy dispersive spectroscopy (EDS) analyzer. The pozzolanic activity of WBA was tested by the Chapelle test and assessment of the Portlandite content used simultaneous thermal analysis (STA). For the hardened mortar samples, a complete set of structural, mechanical, hygric, and thermal parameters was experimentally determined. The mortars with WBA admixing yielded similar or better functional properties than those obtained for traditional pure lime-based plaster, pointing to their presumed application as rendering and walling renovation mortars. As the Chapelle test, STA, and mechanical test proved high pozzolanity of WBA, it was classified as an alternative eco-efficient low-cost pozzolan for use in lime blend-based building materials. The savings in CO2 emissions and energy by the use of WBA as a partial lime hydrate substitute in mortar composition were also highly appreciated with respect to the sustainability of the construction industry.
- Triclofos Sodium for Pediatric Sedation in Non-Painful Neurodiagnostic Studies. [Journal Article]
- PDPaediatr Drugs 2019 Jul 11
- CONCLUSIONS: TFS, when administered in a controlled and monitored environment, may be safe for use in children, including those with underlying neurocognitive disorders.
- Effect of residue substitution via site-directed mutagenesis on activity and steroselectivity of transaminase BpTA from Bacillus pumilus W3 for sitafloxacin hydrate intermediate. [Journal Article]
- IJInt J Biol Macromol 2019 Jul 04; 137:732-740
- Aminotransferases are widely employed as biocatalysts for the asymmetric synthesis of biologically active pharmaceuticals. Transaminase BpTA from Bacillus pumilus W3 can accept a broad spectrum of st…
Aminotransferases are widely employed as biocatalysts for the asymmetric synthesis of biologically active pharmaceuticals. Transaminase BpTA from Bacillus pumilus W3 can accept a broad spectrum of sterically demanding substrates, but it does not process the key five-membered ring intermediate of sitafloxacin. In the present study, we rationally constructed numerous single-point mutants and six multi-point mutants by combining the structural characteristics of transaminase and its substrates. Biochemical characteristics of wild-type and mutant enzymes were initially analyzed, and mutants I215M, I215F, and Y32L displayed increased catalytic efficiency, K155A, I215V and T252A completely lost enzyme activity. Residues K155 and T252 had a particularly strong influence on catalytic activity. Four multi-point mutants (L212M/I215M, Y32L/S190A/L212M/I215M, Y32L/Y159F/T252A and Y32W/Y159F/I215M/T252A) possess potential for industrial production of the key five-membered ring intermediate of sitafloxacin. Furthermore, mutants Y32L/Y159F/T252A and Y32W/Y159F/I215M/T252A can catalyze conversion of (R)-α-phenethylamine, albeit at an extremely low rate (<8%). In summary, mutants L212M/I215M and Y32L/S190A/L212M/I215M are more suitable for industrial production of the antibiotic, sitafloxacin, via an enzymatic approach.
- Methane-fuelled biofilms predominantly composed of methanotrophic ANME-1 in Arctic gas hydrate-related sediments. [Journal Article]
- SRSci Rep 2019 Jul 05; 9(1):9725
- Sedimentary biofilms comprising microbial communities mediating the anaerobic oxidation of methane are rare. Here, we describe two biofilm communities discovered in sediment cores recovered from Arct…
Sedimentary biofilms comprising microbial communities mediating the anaerobic oxidation of methane are rare. Here, we describe two biofilm communities discovered in sediment cores recovered from Arctic cold seep sites (gas hydrate pingos) in the north-western Barents Sea, characterized by steady methane fluxes. We found macroscopically visible biofilms in pockets in the sediment matrix at the depth of the sulphate-methane-transition zone. 16S rRNA gene surveys revealed that the microbial community in one of the two biofilms comprised exclusively of putative anaerobic methanotrophic archaea of which ANME-1 was the sole archaeal taxon. The bacterial community consisted of relatives of sulphate-reducing bacteria (SRB) belonging to uncultured Desulfobacteraceae clustering into SEEP-SRB1 (i.e. the typical SRB associated to ANME-1), and members of the atribacterial JS1 clade. Confocal laser scanning microscopy demonstrates that this biofilm is composed of multicellular strands and patches of ANME-1 that are loosely associated with SRB cells, but not tightly connected in aggregates. Our discovery of methanotrophic biofilms in sediment pockets closely associated with methane seeps constitutes a hitherto overlooked and potentially widespread sink for methane and sulphate in marine sediments.
- Waterborne Polyurethanes as a New and Promising Class of Kinetic Inhibitors for Methane Hydrate Formation. [Journal Article]
- SRSci Rep 2019 Jul 05; 9(1):9797
- A facile, new and promising technique based on waterborne polymers for designing and synthesizing kinetic hydrate inhibitors (KHIs) has been proposed to prevent methane hydrate formation. This topic …
A facile, new and promising technique based on waterborne polymers for designing and synthesizing kinetic hydrate inhibitors (KHIs) has been proposed to prevent methane hydrate formation. This topic is challenging subject in flow assurance problems in gas and oilfields. Proposed technique helps to get KHIs with required number and distance of hydrophilic and hydrophobic groups in molecule and good solubility in water. The performance of these new KHIs was investigated by high pressure micro-differential scanning calorimeter (HP-μDSC) and high-pressure autoclave cell. The results demonstrated the high performance of these inhibitors in delay the induction time (10-20 times) and reduce the hydrate growth rate (3 times). Also they did not increase hydrate dissociation temperature in comparison with pure water and show thermodynamic inhibition as well. Inhibition effect of synthesized polymers is improved with the increase of concentration significantly. Since this is the first report of the use of waterborne polymers as kinetic hydrate inhibitor, we expect that KHIs based on waterborne-based polymers can be a prospective option for preventing methane hydrate formation.
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- Feasibility of a Mobile Health Application To Monitor Recovery and Patient-reported Outcomes after Robot-assisted Radical Prostatectomy. [Journal Article]
- EUEur Urol Oncol 2019; 2(4):425-428
- A mobile application (app) designed on the basis of a literature review and interviews with urologic oncologists was created to help streamline robot-assisted radical prostatectomy care and in compli…
A mobile application (app) designed on the basis of a literature review and interviews with urologic oncologists was created to help streamline robot-assisted radical prostatectomy care and in compliance with quality indicators. Use of the app was limited to English-speaking men with iPhones; 20 of 43 men approached (47%) agreed to participate. Lack of an iPhone was the most common reason for non-enrollment (52%). Preoperatively, men received daily push notifications to perform Kegel exercises and 19 men (95%) completed an Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) questionnaire using the app. After hospital discharge, men completed a postoperative pain questionnaire and received push notifications to ambulate and increase their fluid intake. After catheter removal, daily notifications to perform Kegel exercises and complete weekly EPIC-CP surveys were pushed to monitor recovery of functional outcomes. EPIC-CP and postoperative pain assessment response rates were 75% and 90%, respectively. 85% of the men complied with notifications to ambulate, hydrate, and perform Kegel exercises. The 15 men (75%) who completed the satisfaction survey found the app easy to use and understand, which suggests that mobile apps can be easily implemented perioperatively. Mobile apps have the potential to improve compliance with perioperative instructions and allow more frequent capture of patient-reported outcomes with minimal resource utilization. Patient summary: We examined the use of a mobile application designed to capture patient-reported outcomes and guide postoperative care after major urologic surgery. Mobile apps can be implemented with relative ease and high patient satisfaction.