The Experts below are selected from a list of 183 Experts worldwide ranked by ideXlab platform
Ahmed Al-harrasi - One of the best experts on this subject based on the ideXlab platform.
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Novel Anticancer Dimeric Napthoquiones from Diospyros lotus Having Anti-Tumor, Anti-Inflammatory and Multidrug Resistance Reversal Potential: In Vitro, In Vivo and In Silico Evidence
Anti-cancer agents in medicinal chemistry, 2021Co-Authors: Abdur Rauf, Ajmal Khan, Tareq Abu-izneid, Fahad A. Alhumaydhi, Saud Bawazeer, Muslim Raza, Haroon Khan, Seema Patel, Ahmed Al-harrasiAbstract:Background Cancer being a genetically heterogenous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals. Objective The current study focused on anticancer Potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus. Methods In-vitro Epstein-Barr-Virus (EVA) early antigen activation assay was used to evaluate the antitumor Potential of test compounds followed by two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance Reversal Potential. The in-vitro heat induced protein denaturation assay was used for the anti-inflammatory effect of the test compounds. Results Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th weeks, whereas compound 2 exerted the same effect at 13th weeks, while both provoked 100% effect at 20th weeks. Both compounds significantly attenuated thermal induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of multidrug resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR Reversal effect in a dose-dependent manner against mouse Tlymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard. Conclusions Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR Reversal effects with significant attenuation of thermal induced denaturation of protein. These compounds may explain the traditional uses of D. lotus and might be effective anticancer agents.
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Novel Anticancer Dimeric Napthoquiones from Diospyros lotus Having Anti-Tumor, Anti-Inflammatory and Multidrug Resistance Reversal Potential: In Vitro, In Vivo and In Silico Evidence.
Anti-cancer agents in medicinal chemistry, 2021Co-Authors: Abdur Rauf, Ajmal Khan, Tareq Abu-izneid, Fahad A. Alhumaydhi, Saud Bawazeer, Muslim Raza, Haroon Khan, Seema Patel, Ahmed Al-harrasiAbstract:Cancer being a genetically heterogenous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals. The current study focused on anticancer Potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus. In-vitro Epstein-Barr-Virus (EVA) early antigen activation assay was used to evaluate the antitumor Potential of test compounds followed by two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance Reversal Potential. The in-vitro heat induced protein denaturation assay was used for the anti-inflammatory effect of the test compounds. Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th weeks, whereas compound 2 exerted the same effect at 13th weeks, while both provoked 100% effect at 20th weeks. Both compounds significantly attenuated thermal induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of multidrug resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR Reversal effect in a dose-dependent manner against mouse Tlymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard. Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR Reversal effects with significant attenuation of thermal induced denaturation of protein. These compounds may explain the traditional uses of D. lotus and might be effective anticancer agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
D M Bers - One of the best experts on this subject based on the ideXlab platform.
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Ca2+ influx via the L-type Ca2+ channel during tail current and above current Reversal Potential in ferret ventricular myocytes.
The Journal of physiology, 2000Co-Authors: Z Zhou, D M BersAbstract:1. Current through L-type Ca2+ channels (ICa) was measured electrophysiologically at the same time as Ca2+ influx was measured by trapping entering Ca2+ with a high concentration of indo-1 (> 1 mM) in ferret ventricular myocytes. 2. Na+-free conditions prevented Na+-Ca2+ exchange and K+ currents were blocked by Cs+ and TEA. Thapsigargin (5 microM) prevented Ca2+ uptake and release by the sarcoplasmic reticulum. ICa was pre-activated by brief pulses to +120 mV (the equilibrium Potential for Ca2+, ECa), followed by steps to different membrane Potentials (Em, -80 to +100 mV), in some cases in the presence of the Ca2+ channel agonist FPL-64176. 3. Integrated ICa ( 82 ICa) was linearly related to the change in the concentration of Ca2+ bound to indo-1, which was assessed by the fluorescence difference signal DeltaFd (Fd = F500 - F400). This created an internal calibration of DeltaFd as a measure of Ca2+ influx. 4. The DeltaFd/ 82 ICadt relationship was virtually unchanged at all measurable inward ICa (at Em from -80 to +50 mV). This indicates that the fractional current carried by Ca2+ and channel selectivity are unchanged over this Em range, and also that the selectivity for Ca2+ is very high. 5. Ca2+ influx was readily detected by DeltaFd beyond the ICa Reversal Potential (+65 to +100 mV) and was not abolished until Em was +120 mV (i.e. ECa). This is explained by the fact that inward Ca2+ flux at the ICa Reversal Potential is exactly balanced by outward Cs+ current through the Ca2+ channels and can be described by classic Goldman flux analysis with a Ca2+/Cs+ selectivity of the order of 5000. 6. This result also emphasizes that net Ca2+ influx via Ca2+ channels occurs over a voltage range where the net channel current is outward.
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Ca2+ influx via the L-type Ca2+ channel during tail current and above current Reversal Potential in ferret ventricular myocytes.
The Journal of Physiology, 2000Co-Authors: Z Zhou, D M BersAbstract:Current through L-type Ca2+ channels (ICa) was measured electrophysiologically at the same time as Ca2+ influx was measured by trapping entering Ca2+ with a high concentration of indo-1 (> 1 mm) in ferret ventricular myocytes. Na+-free conditions prevented Na+-Ca2+ exchange and K+ currents were blocked by Cs+ and TEA. Thapsigargin (5 μM) prevented Ca2+ uptake and release by the sarcoplasmic reticulum. ICa was pre-activated by brief pulses to +120 mV (the equilibrium Potential for Ca2+, ECa), followed by steps to different membrane Potentials (Em, −80 to +100 mV), in some cases in the presence of the Ca2+ channel agonist FPL-64176. Integrated ICa (ICa) was linearly related to the change in the concentration of Ca2+ bound to indo-1, which was assessed by the fluorescence difference signal ΔFd (Fd=F500–F400). This created an internal calibration of ΔFd as a measure of Ca2+ influx. The ΔFd/ICadt relationship was virtually unchanged at all measurable inward ICa (at Em from −80 to +50 mV). This indicates that the fractional current carried by Ca2+ and channel selectivity are unchanged over this Em range, and also that the selectivity for Ca2+ is very high. Ca2+ influx was readily detected by ΔFd beyond the ICa Reversal Potential (+65 to +100 mV) and was not abolished until Em was +120 mV (i.e. ECa). This is explained by the fact that inward Ca2+ flux at the ICa Reversal Potential is exactly balanced by outward Cs+ current through the Ca2+ channels and can be described by classic Goldman flux analysis with a Ca2+/Cs+ selectivity of the order of 5000. This result also emphasizes that net Ca2+ influx via Ca2+ channels occurs over a voltage range where the net channel current is outward.
Abdur Rauf - One of the best experts on this subject based on the ideXlab platform.
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Novel Anticancer Dimeric Napthoquiones from Diospyros lotus Having Anti-Tumor, Anti-Inflammatory and Multidrug Resistance Reversal Potential: In Vitro, In Vivo and In Silico Evidence
Anti-cancer agents in medicinal chemistry, 2021Co-Authors: Abdur Rauf, Ajmal Khan, Tareq Abu-izneid, Fahad A. Alhumaydhi, Saud Bawazeer, Muslim Raza, Haroon Khan, Seema Patel, Ahmed Al-harrasiAbstract:Background Cancer being a genetically heterogenous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals. Objective The current study focused on anticancer Potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus. Methods In-vitro Epstein-Barr-Virus (EVA) early antigen activation assay was used to evaluate the antitumor Potential of test compounds followed by two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance Reversal Potential. The in-vitro heat induced protein denaturation assay was used for the anti-inflammatory effect of the test compounds. Results Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th weeks, whereas compound 2 exerted the same effect at 13th weeks, while both provoked 100% effect at 20th weeks. Both compounds significantly attenuated thermal induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of multidrug resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR Reversal effect in a dose-dependent manner against mouse Tlymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard. Conclusions Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR Reversal effects with significant attenuation of thermal induced denaturation of protein. These compounds may explain the traditional uses of D. lotus and might be effective anticancer agents.
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Novel Anticancer Dimeric Napthoquiones from Diospyros lotus Having Anti-Tumor, Anti-Inflammatory and Multidrug Resistance Reversal Potential: In Vitro, In Vivo and In Silico Evidence.
Anti-cancer agents in medicinal chemistry, 2021Co-Authors: Abdur Rauf, Ajmal Khan, Tareq Abu-izneid, Fahad A. Alhumaydhi, Saud Bawazeer, Muslim Raza, Haroon Khan, Seema Patel, Ahmed Al-harrasiAbstract:Cancer being a genetically heterogenous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals. The current study focused on anticancer Potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus. In-vitro Epstein-Barr-Virus (EVA) early antigen activation assay was used to evaluate the antitumor Potential of test compounds followed by two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance Reversal Potential. The in-vitro heat induced protein denaturation assay was used for the anti-inflammatory effect of the test compounds. Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th weeks, whereas compound 2 exerted the same effect at 13th weeks, while both provoked 100% effect at 20th weeks. Both compounds significantly attenuated thermal induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of multidrug resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR Reversal effect in a dose-dependent manner against mouse Tlymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard. Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR Reversal effects with significant attenuation of thermal induced denaturation of protein. These compounds may explain the traditional uses of D. lotus and might be effective anticancer agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Z Zhou - One of the best experts on this subject based on the ideXlab platform.
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Ca2+ influx via the L-type Ca2+ channel during tail current and above current Reversal Potential in ferret ventricular myocytes.
The Journal of physiology, 2000Co-Authors: Z Zhou, D M BersAbstract:1. Current through L-type Ca2+ channels (ICa) was measured electrophysiologically at the same time as Ca2+ influx was measured by trapping entering Ca2+ with a high concentration of indo-1 (> 1 mM) in ferret ventricular myocytes. 2. Na+-free conditions prevented Na+-Ca2+ exchange and K+ currents were blocked by Cs+ and TEA. Thapsigargin (5 microM) prevented Ca2+ uptake and release by the sarcoplasmic reticulum. ICa was pre-activated by brief pulses to +120 mV (the equilibrium Potential for Ca2+, ECa), followed by steps to different membrane Potentials (Em, -80 to +100 mV), in some cases in the presence of the Ca2+ channel agonist FPL-64176. 3. Integrated ICa ( 82 ICa) was linearly related to the change in the concentration of Ca2+ bound to indo-1, which was assessed by the fluorescence difference signal DeltaFd (Fd = F500 - F400). This created an internal calibration of DeltaFd as a measure of Ca2+ influx. 4. The DeltaFd/ 82 ICadt relationship was virtually unchanged at all measurable inward ICa (at Em from -80 to +50 mV). This indicates that the fractional current carried by Ca2+ and channel selectivity are unchanged over this Em range, and also that the selectivity for Ca2+ is very high. 5. Ca2+ influx was readily detected by DeltaFd beyond the ICa Reversal Potential (+65 to +100 mV) and was not abolished until Em was +120 mV (i.e. ECa). This is explained by the fact that inward Ca2+ flux at the ICa Reversal Potential is exactly balanced by outward Cs+ current through the Ca2+ channels and can be described by classic Goldman flux analysis with a Ca2+/Cs+ selectivity of the order of 5000. 6. This result also emphasizes that net Ca2+ influx via Ca2+ channels occurs over a voltage range where the net channel current is outward.
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Ca2+ influx via the L-type Ca2+ channel during tail current and above current Reversal Potential in ferret ventricular myocytes.
The Journal of Physiology, 2000Co-Authors: Z Zhou, D M BersAbstract:Current through L-type Ca2+ channels (ICa) was measured electrophysiologically at the same time as Ca2+ influx was measured by trapping entering Ca2+ with a high concentration of indo-1 (> 1 mm) in ferret ventricular myocytes. Na+-free conditions prevented Na+-Ca2+ exchange and K+ currents were blocked by Cs+ and TEA. Thapsigargin (5 μM) prevented Ca2+ uptake and release by the sarcoplasmic reticulum. ICa was pre-activated by brief pulses to +120 mV (the equilibrium Potential for Ca2+, ECa), followed by steps to different membrane Potentials (Em, −80 to +100 mV), in some cases in the presence of the Ca2+ channel agonist FPL-64176. Integrated ICa (ICa) was linearly related to the change in the concentration of Ca2+ bound to indo-1, which was assessed by the fluorescence difference signal ΔFd (Fd=F500–F400). This created an internal calibration of ΔFd as a measure of Ca2+ influx. The ΔFd/ICadt relationship was virtually unchanged at all measurable inward ICa (at Em from −80 to +50 mV). This indicates that the fractional current carried by Ca2+ and channel selectivity are unchanged over this Em range, and also that the selectivity for Ca2+ is very high. Ca2+ influx was readily detected by ΔFd beyond the ICa Reversal Potential (+65 to +100 mV) and was not abolished until Em was +120 mV (i.e. ECa). This is explained by the fact that inward Ca2+ flux at the ICa Reversal Potential is exactly balanced by outward Cs+ current through the Ca2+ channels and can be described by classic Goldman flux analysis with a Ca2+/Cs+ selectivity of the order of 5000. This result also emphasizes that net Ca2+ influx via Ca2+ channels occurs over a voltage range where the net channel current is outward.
Peter Wenner - One of the best experts on this subject based on the ideXlab platform.
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gabaergic synaptic scaling in embryonic motoneurons is mediated by a shift in the chloride Reversal Potential
The Journal of Neuroscience, 2010Co-Authors: Carlos Gonzalezislas, Miguel Angel Garciabereguiain, Nikolai Chub, Peter WennerAbstract:Homeostatic synaptic plasticity ensures that networks maintain specific levels of activity by regulating synaptic strength in a compensatory manner. When spontaneous network activity was blocked in vivo in the embryonic spinal cord, compensatory increases in excitatory GABAergic synaptic inputs were observed. This homeostatic synaptic strengthening was observed as an increase in the amplitude of GABAergic miniature postsynaptic currents. We find that this process is mediated by an increase in chloride accumulation, which produces a depolarizing shift in the GABAergic Reversal Potential ( E GABA). The findings demonstrate a previously unrecognized mechanism underlying homeostatic synaptic scaling. Similar shifts in E GABA have been described following various forms of neuronal injury, introducing the possibility that these shifts in E GABA represent a homeostatic response.
