Synthesis of Maleimide-Based Enediynes with Cyclopropane Moiety for Enhanced Cytotoxicity under Normoxic and Hypoxic Conditions

2021 ◽  
Author(s):  
Wenbo Wang ◽  
Haotian Lu ◽  
Mengsi Zhang ◽  
Hailong Ma ◽  
Xiaoyu Cheng ◽  
...  
Keyword(s):  
Working Mechanism ◽  
Hypoxic Conditions ◽  
Zwitterionic Intermediate

Myers-Saito cycloaromatization (MSC) is the working mechanism of many natural enediyne antibiotics with high antitumor potency. However, the presence of the equilibrium between diradical and zwitterionic intermediate in MSC severely...

Impact Assessment of Dynamic Characteristics on the Hydraulic Driven Machinery Operation

2018 ◽  
pp. 1-12
Author(s):  
A. D. Terenteva
Keyword(s):  
Dynamic Error ◽  
Total Error ◽  
Soil Layer ◽  
Hydraulic Drive ◽  
Hydraulic Cylinder ◽  
Working Mechanism ◽  
Automated Control ◽  
Vertical Coordinate ◽  
Construction Machinery ◽  
The Difference

In civil engineering in Russia, trenching for utilities is currently under digging. To perform such works, it is necessary to use high-precision construction machinery, because inaccurate performance of works can lead to the break down of existing utilities, thereby affecting the residents of nearby houses and demanding the additional works for renewal.The most universal labour saver to perform construction works is hydraulic driven single-bucket excavators, which provide up to 38% of works. Therefore, to improve technical characteristics that affect the accuracy of the work performed is an important task.High requirements for the performance of works are defined by existing construction regulations: an allowable soil layer to remain is at most 0.05 m. To fulfil such requirements, an exact assessment of the working mechanism position and a trench profile is necessary.Examination of a manually operated digging process shows that an operator provides operations untimely, however an automated control system can solve this problem. Dynamic phenomena in the working mechanism have the greatest impact on the accuracy of the works performed.To assess the bucket digging edge position accuracy, a mathematical model of the working mechanism has been created. Based on the cycle scheme of the working process, the excessive displacements of the hydraulic cylinder rods under the load are taken into account. By the end of the cycle, the difference between the specified and obtained positions along the vertical coordinate has been 0.0892 m.A dynamic error of the hydraulic drive system of the working mechanism is considered as a sum of the error due to excessive displacements of the hydraulic cylinder rods and the error due to delay of the hydraulic drive, with the latter being calculated for the average time of delay taking into account the data available in the literature. The total error of the bucket digging edge position of the working mechanism is 0.1176 m, which is 2 times more than the value of 0.05 mConformity of all the links with specification requirements does not guarantee compliance with the required displacement accuracy of the bucket digging edge, and, thus, the soil layer to remain in the base of the trench can exceed the regulated value of 0.05 m.

Study on the Working Mechanism of Amylosucrase DrAS and Its Stability Engineering

2013 ◽  
Vol 29 (4) ◽  
pp. 286
Author(s):  
Ming LIU ◽  
Ping LI ◽  
Bin LIU ◽  
Jiguo SU ◽  
Cunxin WANG
Keyword(s):  
Working Mechanism

Chronic Hypoxia as a Potential Factor in Human Life-threatening Diseases

2017 ◽  
Vol 10 (4) ◽  
pp. 3759-3762
Author(s):  
Sandhya MNVS ◽  
Vanitha K ◽  
Ramesh A
Keyword(s):  
Chronic Hypoxia ◽  
Atmospheric Oxygen ◽  
Human Life ◽  
The Body ◽  
Cellular Damage ◽  
Otto Warburg ◽  
Regular Treatment ◽  
Breathing Exercises ◽  
Hypoxic Conditions ◽  
Cancerous Cell

The review article focuses on the importance of adequate oxygen levels in the body as cure and therapy for many ailments. It is known that hypoxia is the cause for cellular damage and if it can be applied to major patho-physiology’s, it can be observed that slow and chronic hypoxic conditions are the cause for most of the diseases. On the contrary, providing each cell of the body with proper oxygen may be helpful in maintaining the immunity of the body and therefore treating many disease conditions. This theory, if tested may show positive results in heart related diseases, neuronal disorders, stresses, digestive disorders and the unresolved cancer too. Slow decrease in the levels of atmospheric oxygen could be a reason to induce chronic hypoxia. According to Dr. Otto Warburg, a Noble laurate, a normal cell when deprived of oxygen, may get converted to a cancerous cell, whereas a cancerous cell cannot survive in aerobic conditions. If this part of his research be concentrated on, there could be fruitful results in the treatment of cancer. To maintain adequate levels of oxygen in the body, simple yogic breathing practices are helpful. And to maintain the adequate atmospheric oxygen, trees and plants which cleanse the atmospheric air are useful. Clinical surveys on volunteers who have been practicing regular breathing exercises can prove the fact that proper and concentrated respiration could prevent many diseases. Thus, supplementing breathing exercises along with the regular treatment for cancer patients could be helpful in alleviating cancer and other diseases.

scholarly journals Understanding delayed fluorescence and triplet decays of Protoporphyrin IX under hypoxic conditions

2021 ◽  
Author(s):  
Marek Scholz ◽  
Gauthier Croizat ◽  
Jakub Pšenčík ◽  
Roman Dědic ◽  
Santi Nonell ◽  
...  
Keyword(s):  
Protoporphyrin Ix ◽  
Delayed Fluorescence ◽  
Hypoxic Conditions

scholarly journals A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells

2021 ◽  
Author(s):  
Rashmi Kumari ◽  
Vasumathy R ◽  
Dhanya Sunil ◽  
Raghumani Singh Ningthoujam ◽  
Badri Narain Pandey ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Tumor Hypoxia ◽  
Binding Pocket ◽  
Docking Studies ◽  
Single Step ◽  
Naphthalic Anhydride ◽  
Hypoxic Conditions ◽  
Fluorescence Measurements ◽  
Enzymatic Reduction

AbstractThe bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. Graphical abstract

scholarly journals Olive leaf extract prevents obesity, cognitive decline, and depression and improves exercise capacity in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Toshio Mikami ◽  
Jimmy Kim ◽  
Jonghyuk Park ◽  
Hyowon Lee ◽  
Pongson Yaicharoen ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Exercise Capacity ◽  
Endurance Exercise ◽  
Leaf Extract ◽  
Metabolic Diseases ◽  
Olive Leaf ◽  
Olive Leaf Extract ◽  
Hypoxic Conditions ◽  
G Protein Coupled ◽  
Antioxidant Effects

AbstractObesity is a risk factor for development of metabolic diseases and cognitive decline; therefore, obesity prevention is of paramount importance. Neuronal mitochondrial dysfunction induced by oxidative stress is an important mechanism underlying cognitive decline. Olive leaf extract contains large amounts of oleanolic acid, a transmembrane G protein-coupled receptor 5 (TGR5) agonist, and oleuropein, an antioxidant. Activation of TGR5 results in enhanced mitochondrial biogenesis, which suggests that olive leaf extract may help prevent cognitive decline through its mitochondrial and antioxidant effects. Therefore, we investigated olive leaf extract’s effects on obesity, cognitive decline, depression, and endurance exercise capacity in a mouse model. In physically inactive mice fed a high-fat diet, olive leaf extract administration suppressed increases in fat mass and body weight and prevented cognitive declines, specifically decreased working memory and depressive behaviors. Additionally, olive leaf extract increased endurance exercise capacity under atmospheric and hypoxic conditions. Our study suggests that these promising effects may be related to oleanolic acid’s improvement of mitochondrial function and oleuropein’s increase of antioxidant capacity.

scholarly journals Survival and Proliferation under Severely Hypoxic Microenvironments Using Cell-Laden Oxygenating Hydrogels

2021 ◽  
Vol 12 (2) ◽  
pp. 30
Author(s):  
Shabir Hassan ◽  
Berivan Cecen ◽  
Ramon Peña-Garcia ◽  
Fernanda Roberta Marciano ◽  
Amir K. Miri ◽  
...  
Keyword(s):  
Prolonged Release ◽  
Therapeutic Approaches ◽  
Encapsulated Cells ◽  
Hypoxic Conditions ◽  
Skeletal Myoblasts ◽  
Artificial Tissue ◽  
Delivery Platform ◽  
Living Tissues

Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.

scholarly journals The Long-Lasting Story of One Sensor Development: From Novel Ionophore Design toward the Sensor Selectivity Modeling and Lifetime Improvement

Sensors ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 1401
Author(s):  
Larisa Lvova ◽  
Donato Monti ◽  
Corrado Di Natale ◽  
Roberto Paolesse
Keyword(s):  
Anion Exchanger ◽  
Specific Interaction ◽  
Spectroscopic Studies ◽  
Polymeric Membranes ◽  
Polymeric Membrane ◽  
Active Components ◽  
Nitrite Ion ◽  
Working Mechanism ◽  
Axial Coordination ◽  
Porphyrin Aggregation

The metalloporphyrin ligand bearing incorporated anion-exchanger fragment, 5-[4-(3-trimethylammonium)propyloxyphenyl]-10,15,20-triphenylporphyrinate of Co(II) chloride, CoTPP-N, has been tested as anion-selective ionophore in PVC-based solvent polymeric membrane sensors. A plausible sensor working mechanism includes the axial coordination of the target anion on ionophore metal center followed by the formed complex aggregation with the second ionophore molecule through positively charged anion-exchanger fragment. The UV-visible spectroscopic studies in solution have revealed that the analyte concentration increase induces the J-type porphyrin aggregation. Polymeric membranes doped with CoTPP-N showed close to the theoretical Nernstian response toward nitrite ion, preferably coordinated by the ionophore, and were dependent on the presence of additional membrane-active components (lipophilic ionic sites and ionophore) in the membrane phase. The resulting selectivity was a subject of specific interaction and/or steric factors. Moreover, it was demonstrated theoretically and confirmed experimentally that the selection of a proper ratio of ionophore and anionic additive can optimize the sensor selectivity and lifetime.

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