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Dipankar Sen - One of the best experts on this subject based on the ideXlab platform.
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Effect of other G:C ratios on the formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:(a) Circular dichroism spectra of DNA repeats containing varying C:G ratios, independently incubated and diluted either in 150 mM 4-ethylmorpholine, pH 5.2 (left) or 150 mM Lithium Citrate, pH 5.2 (right); in all cases, given the different molecular weights of different oligonucleotides, the DNA mass was kept equal in each solution; (b) data, as above, but incubated and diluted only in 150 mM Lithium Citrate, pH 5.2.
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C2G4 repeat-length dependence on the formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:CD spectra of d(C2G4)n (where n = 2–7), in 150 mM Lithium Citrate, pH 5.2, at DNA concentrations adjusted to ensure unvarying DNA mass from solution to solution. Each DNA was incubated at 700 μM concentration in 150 mM Lithium Citrate, pH 5.2, at 37°C for 14 hrs, following which it was diluted to ensure constant DNA mass into the same buffer as follows—“7”: 2.85 μM d(C2G4)7; “6”: 3.33 μM d(C2G4)6; “5”: 4.0 μM d(C2G4)5; “4”: 5.0 μM d(C2G4)4; “3”: 6.66 μM d(C2G4)3; and “2”: 10.0 μM d(C2G4)2.
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Effect of varying G:C ratios away from C2G4 on the formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:(a-b) Circular dichroism spectra of DNA repeats containing varying C:G ratios, independently incubated and diluted either in 150 mM 4-ethylmorpholine, pH 5.2 (left) or 150 mM Lithium Citrate, pH 5.2 (right); in all cases, given the different molecular weights of different oligonucleotides, the DNA mass was kept equal in each solution.
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Comparison of iCD-DNA with Z DNA and Z-G4.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:Circular dichroism spectra of (C2G4)7 in 150 mM potassium Citrate, pH 5.2; (C2G4)7 in 150 mM Lithium Citrate pH 5.2; a left-handed G-quadruplex (GQ) [ZG4: (T(GGT)4TG(TGG)3TGTT)] in TE (10mM Tris, 0.1mM EDTA, pH 7.0) plus 150 mM KCl; and a duplex Z-DNA [(CG)25] in TE plus 4.0 M NaCl.
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Formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:(a) Circular dichroism spectra of 20 μM d(C2G4)7 in TE Buffer plus 150 mM LiCl, pH 7.4. 700 μM DNA in this buffer, at 37°C, was incubated for 14 hrs and for 5 days. CD spectra were taken shortly following dilution to 20 μM DNA, in the same buffer, and measured at 22°C. (b) Circular dichroism spectra of 20 μM d(C2G4)7 in 150 mM Lithium Citrate buffer at different pH (5, 5.2, 5.4, 5.6, 6) as well as in TE buffer plus 150 mM LiCl (at pH 7.0 and 7.4). 700 μM DNA, in the above buffers, was incubated for 14 hrs at 37°C. CD spectra were taken shortly after dilution to 20 μM DNA, in the appropriate buffer, and measured at 22°C. (c) θ280 from Fig 1B plotted as a function of pH.
Prince Kumar Lat - One of the best experts on this subject based on the ideXlab platform.
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Effect of other G:C ratios on the formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:(a) Circular dichroism spectra of DNA repeats containing varying C:G ratios, independently incubated and diluted either in 150 mM 4-ethylmorpholine, pH 5.2 (left) or 150 mM Lithium Citrate, pH 5.2 (right); in all cases, given the different molecular weights of different oligonucleotides, the DNA mass was kept equal in each solution; (b) data, as above, but incubated and diluted only in 150 mM Lithium Citrate, pH 5.2.
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C2G4 repeat-length dependence on the formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:CD spectra of d(C2G4)n (where n = 2–7), in 150 mM Lithium Citrate, pH 5.2, at DNA concentrations adjusted to ensure unvarying DNA mass from solution to solution. Each DNA was incubated at 700 μM concentration in 150 mM Lithium Citrate, pH 5.2, at 37°C for 14 hrs, following which it was diluted to ensure constant DNA mass into the same buffer as follows—“7”: 2.85 μM d(C2G4)7; “6”: 3.33 μM d(C2G4)6; “5”: 4.0 μM d(C2G4)5; “4”: 5.0 μM d(C2G4)4; “3”: 6.66 μM d(C2G4)3; and “2”: 10.0 μM d(C2G4)2.
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Effect of varying G:C ratios away from C2G4 on the formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:(a-b) Circular dichroism spectra of DNA repeats containing varying C:G ratios, independently incubated and diluted either in 150 mM 4-ethylmorpholine, pH 5.2 (left) or 150 mM Lithium Citrate, pH 5.2 (right); in all cases, given the different molecular weights of different oligonucleotides, the DNA mass was kept equal in each solution.
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Comparison of iCD-DNA with Z DNA and Z-G4.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:Circular dichroism spectra of (C2G4)7 in 150 mM potassium Citrate, pH 5.2; (C2G4)7 in 150 mM Lithium Citrate pH 5.2; a left-handed G-quadruplex (GQ) [ZG4: (T(GGT)4TG(TGG)3TGTT)] in TE (10mM Tris, 0.1mM EDTA, pH 7.0) plus 150 mM KCl; and a duplex Z-DNA [(CG)25] in TE plus 4.0 M NaCl.
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Formation of iCD-DNA.
2018Co-Authors: Prince Kumar Lat, Dipankar SenAbstract:(a) Circular dichroism spectra of 20 μM d(C2G4)7 in TE Buffer plus 150 mM LiCl, pH 7.4. 700 μM DNA in this buffer, at 37°C, was incubated for 14 hrs and for 5 days. CD spectra were taken shortly following dilution to 20 μM DNA, in the same buffer, and measured at 22°C. (b) Circular dichroism spectra of 20 μM d(C2G4)7 in 150 mM Lithium Citrate buffer at different pH (5, 5.2, 5.4, 5.6, 6) as well as in TE buffer plus 150 mM LiCl (at pH 7.0 and 7.4). 700 μM DNA, in the above buffers, was incubated for 14 hrs at 37°C. CD spectra were taken shortly after dilution to 20 μM DNA, in the appropriate buffer, and measured at 22°C. (c) θ280 from Fig 1B plotted as a function of pH.
Wilma J Friedman - One of the best experts on this subject based on the ideXlab platform.
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a novel neuroprotective mechanism for Lithium that prevents association of the p75ntr sortilin receptor complex and attenuates prongf induced neuronal death in vitro and in vivo
eNeuro, 2018Co-Authors: Shayri G Greenwood, Laura Ester Montroull, Marta Volosin, Helen E Scharfman, Kenneth K Teng, Matthew Light, Risa Torkin, Fredrick R Maxfield, Barbara L Hempstead, Wilma J FriedmanAbstract:Abstract Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified Lithium Citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low, submicromolar doses of Lithium Citrate effectively inhibited proNGF-induced cell death in cultured neurons and protected hippocampal neurons following pilocarpine-induced SE in vivo. We analyzed specific mechanisms by which Lithium Citrate afforded neuroprotection and determined that Lithium Citrate prevented the association and internalization of the p75NTR-sortilin receptor complex. Our results demonstrate a novel mechanism by which low-dose treatments of Lithium Citrate are effective in attenuating p75NTR-mediated cell death in vitro and in vivo.
Yu. I. Torshin - One of the best experts on this subject based on the ideXlab platform.
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Targeted proteins involved in the neuroprotective effects of Lithium Citrate
IMA-PRESS LLC, 2017Co-Authors: Yu. I. Torshin, O. A. Gromova, L. A. Mayorova, Yu. A. VolkovAbstract:Preparations based on organic Lithium salts are promising neuroprotective agents that are effective just in the micromolar concentration range and, at the same time, have high safety (Toxicity Class V).Objective: to elucidate more detailed mechanisms responsible for the biological and pharmacological effects of Lithium Citrate, by analyzing the possible interactions of Lithium ion with human proteome proteins that are also represented in the rat proteome.Material and methods. The targets of Lithium are two proteins, such as glycogen synthase-3β (GSK-3β) and inositol monophosphatase 1 (IMPA1), were experimentally validated using Lithium Citrate.Results. The cycle use of oral Lithium Citrate was shown to decrease the activity of these proteins in the rat brain hydrolysates. The effects of Lithium were analyzed in the human and rat proteomes. 47 proteins were ascertained to be present in the human and rat proteomes, the activity of which depended on Lithium ions. There were 4 groups of Lithium-dependent proteins: 1) the proteins regulated by GSK3β kinase; 2) those modulating the level of inositol phosphates; 3) those modulating the metabolism of neurotransmitters; 4) those working via other mechanisms
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Neuroprotective properties of Lithium salts during glutamate-induced stress
IMA-PRESS LLC, 2017Co-Authors: A. V. Pronin, Yu. I. Torshin, O. A. Gromova, E. V. Stelmashuk, O. P. Aleksandrova, E. E. Genrikhs, L. G. KhaspekovAbstract:Organic Lithium salts are a promising area for searching for effective and safe neuroprotective drugs. By using chronic bilateral common carotid artery occlusion models, the authors have previously found that Lithium gluconate and Lithium Citrate are effective agents to prevent a neurological deficit in brain ischemic or neurodegenerative damages. The use of organic Lithium salts in brain ischemia leads to their targeted accumulation in the frontal lobes of the brain and in the cerebrospinal fluid, normalizing trace elemental homeostasis in the brain Objective: to compare the neuroprotective effects of different Lithium salts (chloride, carbonate, ascorbate, and Citrate).Material and methods. A neurocytological study was performed using a glutamate-induced stress model in cultured granular neurons (CGNs).The state of CGNs was monitored daily and at each experimental stage, by viewing in an inverted phase contrast microscope. The final concentrations of the test substances in the culture medium were 0.1, 0.2, and 0.5, and 1 mM. The survival of CGNs was quantified by directly counting the neurons with intact morphology in 5 fields of vision. Five experiments were carried out for each substance. The number of neurons with intact morphology in the control cultures was taken as 100% survival.Results. Lithium chloride and Lithium carbonate in the studied range of concentrations did not show significant neuroprotective properties.Lithium ascorbate and Lithium Citrate, on the contrary, significantly increased the survival of neurons in mild, moderate and severe glutamateinduced stress. Lithium Citrate at a concentration of 0.2 mM increased the survival rate of CGNs by an average of 30% (p < 0.003). The active neuroprotective principles of Lithium Citrate were shown to be both Lithium ion and Citrate anion. These positive qualities of the test organic Lithium salts are explained primarily by the fact that ascorbate and Citrate anions contribute to the enhanced transport of Lithium ions into the cells through appropriate ion channels for the transport of organic acids (SLC13A5, etc.).Conclusion. Lithium ascorbate and Lithium Citrate were confirmed to have an immediate neuroprotective effect on cerebellar CGNs. Treatment of CGNs with Lithium Citrate showed a 30% increase in cell survival during glutamate-induced stress
O. A. Gromova - One of the best experts on this subject based on the ideXlab platform.
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Targeted proteins involved in the neuroprotective effects of Lithium Citrate
IMA-PRESS LLC, 2017Co-Authors: Yu. I. Torshin, O. A. Gromova, L. A. Mayorova, Yu. A. VolkovAbstract:Preparations based on organic Lithium salts are promising neuroprotective agents that are effective just in the micromolar concentration range and, at the same time, have high safety (Toxicity Class V).Objective: to elucidate more detailed mechanisms responsible for the biological and pharmacological effects of Lithium Citrate, by analyzing the possible interactions of Lithium ion with human proteome proteins that are also represented in the rat proteome.Material and methods. The targets of Lithium are two proteins, such as glycogen synthase-3β (GSK-3β) and inositol monophosphatase 1 (IMPA1), were experimentally validated using Lithium Citrate.Results. The cycle use of oral Lithium Citrate was shown to decrease the activity of these proteins in the rat brain hydrolysates. The effects of Lithium were analyzed in the human and rat proteomes. 47 proteins were ascertained to be present in the human and rat proteomes, the activity of which depended on Lithium ions. There were 4 groups of Lithium-dependent proteins: 1) the proteins regulated by GSK3β kinase; 2) those modulating the level of inositol phosphates; 3) those modulating the metabolism of neurotransmitters; 4) those working via other mechanisms
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Neuroprotective properties of Lithium salts during glutamate-induced stress
IMA-PRESS LLC, 2017Co-Authors: A. V. Pronin, Yu. I. Torshin, O. A. Gromova, E. V. Stelmashuk, O. P. Aleksandrova, E. E. Genrikhs, L. G. KhaspekovAbstract:Organic Lithium salts are a promising area for searching for effective and safe neuroprotective drugs. By using chronic bilateral common carotid artery occlusion models, the authors have previously found that Lithium gluconate and Lithium Citrate are effective agents to prevent a neurological deficit in brain ischemic or neurodegenerative damages. The use of organic Lithium salts in brain ischemia leads to their targeted accumulation in the frontal lobes of the brain and in the cerebrospinal fluid, normalizing trace elemental homeostasis in the brain Objective: to compare the neuroprotective effects of different Lithium salts (chloride, carbonate, ascorbate, and Citrate).Material and methods. A neurocytological study was performed using a glutamate-induced stress model in cultured granular neurons (CGNs).The state of CGNs was monitored daily and at each experimental stage, by viewing in an inverted phase contrast microscope. The final concentrations of the test substances in the culture medium were 0.1, 0.2, and 0.5, and 1 mM. The survival of CGNs was quantified by directly counting the neurons with intact morphology in 5 fields of vision. Five experiments were carried out for each substance. The number of neurons with intact morphology in the control cultures was taken as 100% survival.Results. Lithium chloride and Lithium carbonate in the studied range of concentrations did not show significant neuroprotective properties.Lithium ascorbate and Lithium Citrate, on the contrary, significantly increased the survival of neurons in mild, moderate and severe glutamateinduced stress. Lithium Citrate at a concentration of 0.2 mM increased the survival rate of CGNs by an average of 30% (p < 0.003). The active neuroprotective principles of Lithium Citrate were shown to be both Lithium ion and Citrate anion. These positive qualities of the test organic Lithium salts are explained primarily by the fact that ascorbate and Citrate anions contribute to the enhanced transport of Lithium ions into the cells through appropriate ion channels for the transport of organic acids (SLC13A5, etc.).Conclusion. Lithium ascorbate and Lithium Citrate were confirmed to have an immediate neuroprotective effect on cerebellar CGNs. Treatment of CGNs with Lithium Citrate showed a 30% increase in cell survival during glutamate-induced stress