The role of salt-inducible kinases on the modulation of renal and intestinal Na < sup > + < /sup > ,K < sup > + < /sup > -ATPase activity during short- and long-term high-salt intake
Eur J Pharmacol. 2021 May 11:174153. doi: 10.1016/j.ejphar.2021.174153. Online ahead of print.ABSTRACTType 1 salt-inducible kinases (SIK1) has been shown to act as a mediator during the cellular adaptation to variations in intracellular sodium in a variety of cell types. Type 2 SIK (SIK2) modulates various biological functions and acts as a signal transmitter in various pathways. To evaluate the role of both SIK isoforms in renal and intestinal Na+,K+-ATPase (NKA) activity, we made use of constitutive sik1-/- (SIK1-KO), sik2-/- (SIK2-KO), double sik1-/-sik2-/- (double SIK1*2-KO) knockout and wild-type (WT) mice challenged ...
Source: European Journal of Pharmacology - May 14, 2021 Category: Drugs & Pharmacology Authors: Tatiana Ant ónio Dina Cosme Bruno Igreja S ónia Fraga Maria Paula Serr ão Nuno M Pires Patr ício Soares-da-Silva Source Type: research

Ouabain worsens diastolic sarcomere length in myocytes from a cardiomyopathy mouse model
In this study, we tested the acute effects of ouabain on ventricular myocytes of an HCM mouse model. The effects of ouabain on contractility and Ca2+ transients were tested in intact adult mouse ventricular myocytes (AMVMs) of Mybpc3-targeted knock-in (KI) and wild-type (WT) mice. Concentration-response assessment of contractile function revealed low sensitivity of AMVMs to ouabain (10 μM) compared to literature data on human cardiomyocytes (100 nM). Three hundred μM ouabain increased contraction amplitude (WT ∼1.8-fold; KI ∼1.5-fold) and diastolic intracellular Ca2+ in both WT and KI (+12-18 %), but further ...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Silke D üsener Frederik Flenner Christoph Maack Michael Kohlhaas Johannes Bay Lucie Carrier Felix W Friedrich Source Type: research

Losartan protects endothelium-dependent relaxation in vivo in a murine model of rheumatoid arthritis
Eur J Pharmacol. 2021 May 10:174133. doi: 10.1016/j.ejphar.2021.174133. Online ahead of print.ABSTRACTAngiotensin II-type 1 receptor stimulation is recognised to promote inflammation, a state central to the development and maintenance of rheumatoid arthritis. Herein we examined the use of losartan, an angiotensin II-type 1 receptor antagonist, on vascular reactivity, knee joint diameter and behavioural assessment of pain in a Freund's complete adjuvant (FCA) mouse model of joint inflammation. Monoarthritis was induced via FCA in the presence or absence of losartan with naive mice serving as controls. Knee joint swelling, j...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Moanna Villaluz Lynette Dunning Carl S Goodyear William R Ferrell John C Lockhart Andrew MacKenzie Source Type: research

Current progress on the mechanisms of hyperhomocysteinemia-induced vascular injury and use of natural polyphenol compounds
Eur J Pharmacol. 2021 May 10:174168. doi: 10.1016/j.ejphar.2021.174168. Online ahead of print.ABSTRACTCardiovascular disease is one of the most common diseases in the elderly population, and its incidence has rapidly increased with the prolongation of life expectancy. Hyperhomocysteinemia is an independent risk factor for various cardiovascular diseases, including atherosclerosis, and damage to vascular function plays an initial role in its pathogenesis. This review presents the latest knowledge on the mechanisms of vascular injury caused by hyperhomocysteinemia, including oxidative stress, endoplasmic reticulum stress, pr...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Qiao Jiang Li Wang Xu Si Jin-Long Tian Ye Zhang Hai-Long Gui Bin Li De-Hong Tan Source Type: research

"The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics"
Eur J Pharmacol. 2021 May 10:174169. doi: 10.1016/j.ejphar.2021.174169. Online ahead of print.ABSTRACTDiabetes, characterized by high glucose levels, has been listed to be one of the world's major causes of death. Around 1.6 million deaths are attributed to this disease each year. Persistent hyperglycemic conditions in diabetic patients affect various organs of the body leading to diabetic complications and worsen the disease condition. Current treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4(dipeptidyl peptidase-4) and GLP...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Prabhsimran Kaur Bidwan Sekhar Behera Sandeep Singh Anjana Munshi Source Type: research

Ouabain worsens diastolic sarcomere length in myocytes from a cardiomyopathy mouse model
In this study, we tested the acute effects of ouabain on ventricular myocytes of an HCM mouse model. The effects of ouabain on contractility and Ca2+ transients were tested in intact adult mouse ventricular myocytes (AMVMs) of Mybpc3-targeted knock-in (KI) and wild-type (WT) mice. Concentration-response assessment of contractile function revealed low sensitivity of AMVMs to ouabain (10 μM) compared to literature data on human cardiomyocytes (100 nM). Three hundred μM ouabain increased contraction amplitude (WT ∼1.8-fold; KI ∼1.5-fold) and diastolic intracellular Ca2+ in both WT and KI (+12-18 %), but further ...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Silke D üsener Frederik Flenner Christoph Maack Michael Kohlhaas Johannes Bay Lucie Carrier Felix W Friedrich Source Type: research

Losartan protects endothelium-dependent relaxation in vivo in a murine model of rheumatoid arthritis
Eur J Pharmacol. 2021 May 10:174133. doi: 10.1016/j.ejphar.2021.174133. Online ahead of print.ABSTRACTAngiotensin II-type 1 receptor stimulation is recognised to promote inflammation, a state central to the development and maintenance of rheumatoid arthritis. Herein we examined the use of losartan, an angiotensin II-type 1 receptor antagonist, on vascular reactivity, knee joint diameter and behavioural assessment of pain in a Freund's complete adjuvant (FCA) mouse model of joint inflammation. Monoarthritis was induced via FCA in the presence or absence of losartan with naive mice serving as controls. Knee joint swelling, j...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Moanna Villaluz Lynette Dunning Carl S Goodyear William R Ferrell John C Lockhart Andrew MacKenzie Source Type: research

Current progress on the mechanisms of hyperhomocysteinemia-induced vascular injury and use of natural polyphenol compounds
Eur J Pharmacol. 2021 May 10:174168. doi: 10.1016/j.ejphar.2021.174168. Online ahead of print.ABSTRACTCardiovascular disease is one of the most common diseases in the elderly population, and its incidence has rapidly increased with the prolongation of life expectancy. Hyperhomocysteinemia is an independent risk factor for various cardiovascular diseases, including atherosclerosis, and damage to vascular function plays an initial role in its pathogenesis. This review presents the latest knowledge on the mechanisms of vascular injury caused by hyperhomocysteinemia, including oxidative stress, endoplasmic reticulum stress, pr...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Qiao Jiang Li Wang Xu Si Jin-Long Tian Ye Zhang Hai-Long Gui Bin Li De-Hong Tan Source Type: research

"The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics"
Eur J Pharmacol. 2021 May 10:174169. doi: 10.1016/j.ejphar.2021.174169. Online ahead of print.ABSTRACTDiabetes, characterized by high glucose levels, has been listed to be one of the world's major causes of death. Around 1.6 million deaths are attributed to this disease each year. Persistent hyperglycemic conditions in diabetic patients affect various organs of the body leading to diabetic complications and worsen the disease condition. Current treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4(dipeptidyl peptidase-4) and GLP...
Source: European Journal of Pharmacology - May 13, 2021 Category: Drugs & Pharmacology Authors: Prabhsimran Kaur Bidwan Sekhar Behera Sandeep Singh Anjana Munshi Source Type: research

Role of pyroptosis in diabetic retinopathy and its therapeutic implications
Eur J Pharmacol. 2021 May 9:174166. doi: 10.1016/j.ejphar.2021.174166. Online ahead of print.ABSTRACTPyroptosis has recently been established as a term of programmed-inflammatory cell death. Pyroptosis is mainly divided into two molecular signaling pathways, including caspase-1-dependent canonical and caspase-4/5/11-dependent non-canonical inflammasome pathways. Extensive investigations have reported inflammasome activation facilitates the maturation and secretion of the inflammatory factors interleukin-1β/18 (IL-1β/18), cleavage of gasdermin D (GSDMD), and leading to the stimulation of pyroptosis-mediated cell d...
Source: European Journal of Pharmacology - May 12, 2021 Category: Drugs & Pharmacology Authors: Abdullah Al Mamun Anjuman Ara Mimi Muhammad Zaeem Yanqing Wu Ilma Monalisa Afroza Akter Fahad Munir Jian Xiao Source Type: research

IL-6 deficiency promotes colitis by recruiting Ly6C < sup > hi < /sup > monocytes into inflamed colon tissues in a CCL2-CCR2-dependent manner
This study aimed to investigate the effect of IL-6 in ulcerative colitis in Il6-/- mice. Results indicated that physiological deficiency of IL-6 promoted the development of colitis. Moreover, IL-6 deficiency significantly increased the mRNA levels of monocytes chemokine Ccl2 and its receptor Ccr2 in colon tissues. Similarly, the percentage of Ly6Chigh monocytes and neutrophils were increased in the colon of Il6-/- mice. Intestinal crypts more strongly increased the migration of Il6-/- macrophages than wild-type ones. Moreover, Il6-/- macrophages promoted the migration of neutrophils. Most importantly, RS102895, an antagoni...
Source: European Journal of Pharmacology - May 12, 2021 Category: Drugs & Pharmacology Authors: Qiuhua Cao Yanting Lin Chongxiu Yue Yue Wang Fei Quan Xinmeng Cui Ran Bi Xinying Tang Yong Yang Chen Wang Xianjing Li Xinghua Gao Source Type: research

Role of pyroptosis in diabetic retinopathy and its therapeutic implications
Eur J Pharmacol. 2021 May 9:174166. doi: 10.1016/j.ejphar.2021.174166. Online ahead of print.ABSTRACTPyroptosis has recently been established as a term of programmed-inflammatory cell death. Pyroptosis is mainly divided into two molecular signaling pathways, including caspase-1-dependent canonical and caspase-4/5/11-dependent non-canonical inflammasome pathways. Extensive investigations have reported inflammasome activation facilitates the maturation and secretion of the inflammatory factors interleukin-1β/18 (IL-1β/18), cleavage of gasdermin D (GSDMD), and leading to the stimulation of pyroptosis-mediated cell d...
Source: European Journal of Pharmacology - May 12, 2021 Category: Drugs & Pharmacology Authors: Abdullah Al Mamun Anjuman Ara Mimi Muhammad Zaeem Yanqing Wu Ilma Monalisa Afroza Akter Fahad Munir Jian Xiao Source Type: research

IL-6 deficiency promotes colitis by recruiting Ly6C < sup > hi < /sup > monocytes into inflamed colon tissues in a CCL2-CCR2-dependent manner
This study aimed to investigate the effect of IL-6 in ulcerative colitis in Il6-/- mice. Results indicated that physiological deficiency of IL-6 promoted the development of colitis. Moreover, IL-6 deficiency significantly increased the mRNA levels of monocytes chemokine Ccl2 and its receptor Ccr2 in colon tissues. Similarly, the percentage of Ly6Chigh monocytes and neutrophils were increased in the colon of Il6-/- mice. Intestinal crypts more strongly increased the migration of Il6-/- macrophages than wild-type ones. Moreover, Il6-/- macrophages promoted the migration of neutrophils. Most importantly, RS102895, an antagoni...
Source: European Journal of Pharmacology - May 12, 2021 Category: Drugs & Pharmacology Authors: Qiuhua Cao Yanting Lin Chongxiu Yue Yue Wang Fei Quan Xinmeng Cui Ran Bi Xinying Tang Yong Yang Chen Wang Xianjing Li Xinghua Gao Source Type: research

New generation ENaC inhibitors detach cystic fibrosis airway mucus bundles via Sodium/Hydrogen Exchanger inhibition
Eur J Pharmacol. 2021 May 8:174123. doi: 10.1016/j.ejphar.2021.174123. Online ahead of print.ABSTRACTCystic fibrosis (CF) is a recessive inherited disease caused by mutations affecting anion transport by the epithelial ion channel cystic fibrosis transmembrane conductance regulator (CFTR). The disease is characterized by mucus accumulation in the airways and intestine, but the major cause of mortality in CF is airway mucus accumulation, leading to bacterial colonization, inflammation and respiratory failure. Several drug targets are under evaluation to alleviate airway mucus obstruction in CF and one of these targets is th...
Source: European Journal of Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Authors: Melania Giorgetti Nikolai Klymiuk Andrea B ähr Martin Hemmerling Lisa Jinton Robert Tarran Anna Malmgren Annika Åstrand Gunnar C Hansson Anna Ermund Source Type: research

Effects of trans-resveratrol on type 1 diabetes-induced up-regulation of apoptosis and mitogen-activated protein kinase signaling in retinal pigment epithelium of Dark Agouti rats
In conclusion, Trans-resveratrol-induced alterations in gene expressions do not seem to affect RPE functions as they do not reflect as altered protein functions. Trans-resveratrol imparts its protective effects by normalizing apoptosis-related proteins and ERK1 but does not affect JNK proteins. Trans-resveratrol causes cytostasis in RPE of normal rats by upregulating Bcl2 protein and apoptotic proteins.PMID:33974882 | DOI:10.1016/j.ejphar.2021.174167 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Authors: Heba Al-Hussaini Rawan Sharhabeel Kittaneh Narayana Kilarkaje Source Type: research

Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms
Eur J Pharmacol. 2021 May 7:174156. doi: 10.1016/j.ejphar.2021.174156. Online ahead of print.ABSTRACT3,4-methylenedioxymethamphetamine or MDMA (known as "ecstasy") is a recreational drug of abuse, popular worldwide for its distinctive psychotropic effects. Currently, the therapeutic potential of MDMA in psychotherapy has attracted a lot of interest from the scientific community, despite the multitude of effects that this drug of abuse elicits on the human body. While neuronal effects have been the most studied, cardiovascular effects have also been described, as increased blood pressure and heart rate are the mos...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Diogo A Fonseca Daniel M Ribeiro Margarida Tapadas Maria Dulce Cotrim Source Type: research

Methylglyoxal augments uridine diphosphate-induced contraction via activation of p38 mitogen-activated protein kinase in rat carotid artery
This study aimed to evaluate the relationship between methylglyoxal and uridine diphosphate-induced carotid arterial contraction in rats. Additionally, we examined whether p38 mitogen-activated protein kinase (MAPK) would involve such responses. Organ baths were conducted to determine vascular reactivity in isolated carotid arterial rings, and western blotting was used for protein analysis. Treatment with methylglyoxal to carotid arterial rings showed concentration-dependent augmentation to uridine diphosphate-induced contraction in the absence and presence of NG-nitro-L-arginine, which is a nitric oxide synthase inhibitor...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Takayuki Matsumoto Tomoki Katome Mihoka Kojima Keisuke Takayanagi Kumiko Taguchi Tsuneo Kobayashi Source Type: research

Inhibition of voltage-dependent K < sup > + < /sup > channels in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic agent lorcainide
Eur J Pharmacol. 2021 May 7:174158. doi: 10.1016/j.ejphar.2021.174158. Online ahead of print.ABSTRACTVoltage-dependent K+ (Kv) channels play the role of returning the membrane potential to the resting state, thereby maintaining the vascular tone. Here, we used native smooth-muscle cells from rabbit coronary arteries to investigate the inhibitory effect of lorcainide, a class Ic antiarrhythmic agent, on Kv channels. Lorcainide inhibited Kv channels in a concentration-dependent manner with an IC50 of 4.46 ± 0.15 μM and a Hill coefficient of 0.95 ± 0.01. Although application of lorcainide did not change the a...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Hongliang Li Wenwen Zhuang Mi Seon Seo Jin Ryeol An Yongqi Yang Yiwen Zha Jingyan Liang Zheng-Xin Xu Won Sun Park Source Type: research

Advantages and disadvantages of disulfiram coadministered with popular addictive substances
Eur J Pharmacol. 2021 May 7:174143. doi: 10.1016/j.ejphar.2021.174143. Online ahead of print.ABSTRACTDisulfiram (DSF) is a well-known anti-alcohol agent that inhibits aldehyde dehydrogenase and results in extreme 'hangover' symptoms when consumed with alcohol. This drug, however, has been suggested as useful in other forms of drug addiction due to its beneficial potential in both drug abuse reduction and withdrawal. However, among other drugs used in alcohol dependence, it carries the greatest risk of pharmacological interactions. Concomitant use of DSF and central nervous system stimulants usually leads to harmful, undesi...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Patrycja Kleczkowska Dorota Sulejczak Malgorzata Zaremba Source Type: research

Melatonin Postconditioning Ameliorates Anoxia/Reoxygenation Injury by Regulating Mitophagy and Mitochondrial Dynamics in a SIRT3-Dependent Manner
Eur J Pharmacol. 2021 May 7:174157. doi: 10.1016/j.ejphar.2021.174157. Online ahead of print.ABSTRACTIschaemia/reperfusion (I/R) injury is accompanied by excessive mitochondrial autophagy (mitophagy) and an imbalance in mitochondrial dynamics. Melatonin has been reported to alleviate I/R injury by regulating mitophagy and mitochondrial dynamics. However, the underlying mechanism associated with this activity is not fully understood. The goal of the present study was to investigate whether and how melatonin administration at the beginning of reoxygenation exerts protective effects by regulating mitophagy and mitochondrial d...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Yang Bai Yanli Yang Yafen Gao Duomao Lin Zhaoqi Wang Jun Ma Source Type: research

Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms
Eur J Pharmacol. 2021 May 7:174156. doi: 10.1016/j.ejphar.2021.174156. Online ahead of print.ABSTRACT3,4-methylenedioxymethamphetamine or MDMA (known as "ecstasy") is a recreational drug of abuse, popular worldwide for its distinctive psychotropic effects. Currently, the therapeutic potential of MDMA in psychotherapy has attracted a lot of interest from the scientific community, despite the multitude of effects that this drug of abuse elicits on the human body. While neuronal effects have been the most studied, cardiovascular effects have also been described, as increased blood pressure and heart rate are the mos...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Diogo A Fonseca Daniel M Ribeiro Margarida Tapadas Maria Dulce Cotrim Source Type: research

Methylglyoxal augments uridine diphosphate-induced contraction via activation of p38 mitogen-activated protein kinase in rat carotid artery
This study aimed to evaluate the relationship between methylglyoxal and uridine diphosphate-induced carotid arterial contraction in rats. Additionally, we examined whether p38 mitogen-activated protein kinase (MAPK) would involve such responses. Organ baths were conducted to determine vascular reactivity in isolated carotid arterial rings, and western blotting was used for protein analysis. Treatment with methylglyoxal to carotid arterial rings showed concentration-dependent augmentation to uridine diphosphate-induced contraction in the absence and presence of NG-nitro-L-arginine, which is a nitric oxide synthase inhibitor...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Takayuki Matsumoto Tomoki Katome Mihoka Kojima Keisuke Takayanagi Kumiko Taguchi Tsuneo Kobayashi Source Type: research

Inhibition of voltage-dependent K < sup > + < /sup > channels in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic agent lorcainide
Eur J Pharmacol. 2021 May 7:174158. doi: 10.1016/j.ejphar.2021.174158. Online ahead of print.ABSTRACTVoltage-dependent K+ (Kv) channels play the role of returning the membrane potential to the resting state, thereby maintaining the vascular tone. Here, we used native smooth-muscle cells from rabbit coronary arteries to investigate the inhibitory effect of lorcainide, a class Ic antiarrhythmic agent, on Kv channels. Lorcainide inhibited Kv channels in a concentration-dependent manner with an IC50 of 4.46 ± 0.15 μM and a Hill coefficient of 0.95 ± 0.01. Although application of lorcainide did not change the a...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Hongliang Li Wenwen Zhuang Mi Seon Seo Jin Ryeol An Yongqi Yang Yiwen Zha Jingyan Liang Zheng-Xin Xu Won Sun Park Source Type: research

Advantages and disadvantages of disulfiram coadministered with popular addictive substances
Eur J Pharmacol. 2021 May 7:174143. doi: 10.1016/j.ejphar.2021.174143. Online ahead of print.ABSTRACTDisulfiram (DSF) is a well-known anti-alcohol agent that inhibits aldehyde dehydrogenase and results in extreme 'hangover' symptoms when consumed with alcohol. This drug, however, has been suggested as useful in other forms of drug addiction due to its beneficial potential in both drug abuse reduction and withdrawal. However, among other drugs used in alcohol dependence, it carries the greatest risk of pharmacological interactions. Concomitant use of DSF and central nervous system stimulants usually leads to harmful, undesi...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Patrycja Kleczkowska Dorota Sulejczak Malgorzata Zaremba Source Type: research

Melatonin Postconditioning Ameliorates Anoxia/Reoxygenation Injury by Regulating Mitophagy and Mitochondrial Dynamics in a SIRT3-Dependent Manner
Eur J Pharmacol. 2021 May 7:174157. doi: 10.1016/j.ejphar.2021.174157. Online ahead of print.ABSTRACTIschaemia/reperfusion (I/R) injury is accompanied by excessive mitochondrial autophagy (mitophagy) and an imbalance in mitochondrial dynamics. Melatonin has been reported to alleviate I/R injury by regulating mitophagy and mitochondrial dynamics. However, the underlying mechanism associated with this activity is not fully understood. The goal of the present study was to investigate whether and how melatonin administration at the beginning of reoxygenation exerts protective effects by regulating mitophagy and mitochondrial d...
Source: European Journal of Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Authors: Yang Bai Yanli Yang Yafen Gao Duomao Lin Zhaoqi Wang Jun Ma Source Type: research

Design and biological evaluation of novel long-acting adalimumab Fab conjugated with the albumin binding domain
In this study, to mitigate the poor pharmacokinetics of adalimumab Fab targeting tumor necrosis factor-α (TNFα), an ABD fusion strategy was applied innovatively using GA3, ABD035, ABD094 and ABDCon with high affinities for albumin. The prokaryotic expression, bioactivities and half-lives of those novel Fab-ABD fusions were investigated in vitro and in vivo. All Fab-ABD fusions were successfully purified, and they retained similar TNFα-binding activities with the unmodified Fab control, also presented high affinities for human/mouse serum albumin (HSA/MSA). Additionally, the simultaneous binding of the dif...
Source: European Journal of Pharmacology - May 8, 2021 Category: Drugs & Pharmacology Authors: Qingbin Zhang Mengxin Qian Yong Wu Yapeng Wang Wenwen Shangguan Jianguang Lu Wenjie Zhao Jun Feng Source Type: research

A Comprehensive Review on Pharmacology of Efflux Pumps and their Inhibitors in Antibiotic Resistance
Eur J Pharmacol. 2021 May 5:174151. doi: 10.1016/j.ejphar.2021.174151. Online ahead of print.ABSTRACTThe potential for the build-up of resistance to a particular antibiotic endangers its therapeutic application over time. In recent decades, antibiotic resistance has become one of the most severe threats to public health. It can be attributed to the relentless and unchecked use of antibiotics in healthcare sectors, cell culture, animal husbandry, and agriculture. Some classic examples of resistance mechanisms employed by bacteria include developing antibiotic degrading enzymes, modifying target sites previously targeted by ...
Source: European Journal of Pharmacology - May 8, 2021 Category: Drugs & Pharmacology Authors: Vaibhav Thakur Ankit Uniyal Vinod Tiwari Source Type: research

Design and biological evaluation of novel long-acting adalimumab Fab conjugated with the albumin binding domain
In this study, to mitigate the poor pharmacokinetics of adalimumab Fab targeting tumor necrosis factor-α (TNFα), an ABD fusion strategy was applied innovatively using GA3, ABD035, ABD094 and ABDCon with high affinities for albumin. The prokaryotic expression, bioactivities and half-lives of those novel Fab-ABD fusions were investigated in vitro and in vivo. All Fab-ABD fusions were successfully purified, and they retained similar TNFα-binding activities with the unmodified Fab control, also presented high affinities for human/mouse serum albumin (HSA/MSA). Additionally, the simultaneous binding of the dif...
Source: European Journal of Pharmacology - May 8, 2021 Category: Drugs & Pharmacology Authors: Qingbin Zhang Mengxin Qian Yong Wu Yapeng Wang Wenwen Shangguan Jianguang Lu Wenjie Zhao Jun Feng Source Type: research

A Comprehensive Review on Pharmacology of Efflux Pumps and their Inhibitors in Antibiotic Resistance
Eur J Pharmacol. 2021 May 5:174151. doi: 10.1016/j.ejphar.2021.174151. Online ahead of print.ABSTRACTThe potential for the build-up of resistance to a particular antibiotic endangers its therapeutic application over time. In recent decades, antibiotic resistance has become one of the most severe threats to public health. It can be attributed to the relentless and unchecked use of antibiotics in healthcare sectors, cell culture, animal husbandry, and agriculture. Some classic examples of resistance mechanisms employed by bacteria include developing antibiotic degrading enzymes, modifying target sites previously targeted by ...
Source: European Journal of Pharmacology - May 8, 2021 Category: Drugs & Pharmacology Authors: Vaibhav Thakur Ankit Uniyal Vinod Tiwari Source Type: research

The role of CD44 in cancer chemoresistance: a concise review
Eur J Pharmacol. 2021 May 4:174147. doi: 10.1016/j.ejphar.2021.174147. Online ahead of print.ABSTRACTCD44 is a cell surface adhesion molecule, which is overexpressed on cancer stem cells. The interaction of CD44 with hyaluronan is responsible for tumor development, metastasis, and expression of the chemoresistant phenotype. The overexpression of CD44 impedes the cytotoxic effect of chemotherapy medications in various cancers. Therefore, the high expression of CD44 is associated with a poor prognosis in affected patients. This high expression of CD44 in various cancers has provided an ample opportunity for the treatment of ...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Zohreh Yaghobi Aliakbar Movassaghpour Mehdi Talebi Mahdi Abdoli Shadbad Khalil Hajiasgharzadeh Shiva Pourvahdani Behzad Baradaran Source Type: research

Time-dependent changes in striatal monoamine levels and gene expression following single and repeated amphetamine administration in rats
Eur J Pharmacol. 2021 May 4:174148. doi: 10.1016/j.ejphar.2021.174148. Online ahead of print.ABSTRACTAs drug addiction may result from pathological usurpations of learning and memory's neural mechanisms, we focused on the amphetamine-induced time-dependent neurochemical changes associated with neural plasticity. We used juvenile rats as the risk for drug abuse is higher during adolescence. Experiment 1 served to define the appropriate amphetamine dose and the neurochemical effects of a single administration. In experiment 2, rats received seven amphetamine or saline injections in the open-field test throughout a twelve-day...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Andrey Sequeira-Cordero Juan C Brenes Source Type: research

Molecular mechanism of apelin-13 regulation of colonic motility in rats
In conclusion, apelin-13 inhibited the spontaneous contractile activity of isolated rat colons via the suppression of L-type calcium channels and BKCa channels in colonic smooth muscle cells.PMID:33961873 | DOI:10.1016/j.ejphar.2021.174149 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Lin Yan Haixia Ren Fangting Yuan Wenyao Shi Ying Wang Hesheng Luo Source Type: research

ERK1/2 kinases and dopamine D2 receptors participate in the anticonvulsant effects of a new derivative of benzoylpyridine oxime and valproic acid
Eur J Pharmacol. 2021 May 4:174150. doi: 10.1016/j.ejphar.2021.174150. Online ahead of print.ABSTRACTInhibition of the activity of extracellular signal-regulated kinases (ERK1/2) induced by the activation of the dopamine D2 receptor signalling cascade may be a promising pharmacological target. The aim of this work was to study the involvement of ERK1/2 and dopamine D2 receptor in the mechanism of the anticonvulsant action of valproic acid (VA) and a new benzoylpyridine oxime derivative (GIZH-298), which showed antiepileptic activity in different models of epilepsy. We showed that subchronic exposure to maximal electroshock...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Svetlana A Litvinova Tat'yana A Voronina Evgeny A Kondrakhin Igor O Gaydukov Artem I Davletshin Ekaterina V Vasil'eva Georgy I Kovalev David G Garbuz Source Type: research

Metformin protects against neuroinflammation through integrated mechanisms of miR-141 and the NF- ĸB-mediated inflammasome pathway in a diabetic mouse model
Eur J Pharmacol. 2021 May 4:174146. doi: 10.1016/j.ejphar.2021.174146. Online ahead of print.ABSTRACTThe brain responds to diabetic stress by inducing the inflammatory response. Under normal circumstances this process is tightly regulated. However, uncontrolled inflammatory responses lead to compromised function and eventual neurodegeneration. The microRNA (miR)-200 family, specifically miR-141, is differentially expressed in diseased states including cognitive decline, thereby triggering changes in downstream genes. We hypothesised that Metformin (MF) regulates the miR-141/protein phosphatase 2A (PP2A) axis, and associate...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Taskeen Fathima Docrat Savania Nagiah Anil A Chuturgoon Source Type: research

The role of CD44 in cancer chemoresistance: a concise review
Eur J Pharmacol. 2021 May 4:174147. doi: 10.1016/j.ejphar.2021.174147. Online ahead of print.ABSTRACTCD44 is a cell surface adhesion molecule, which is overexpressed on cancer stem cells. The interaction of CD44 with hyaluronan is responsible for tumor development, metastasis, and expression of the chemoresistant phenotype. The overexpression of CD44 impedes the cytotoxic effect of chemotherapy medications in various cancers. Therefore, the high expression of CD44 is associated with a poor prognosis in affected patients. This high expression of CD44 in various cancers has provided an ample opportunity for the treatment of ...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Zohreh Yaghobi Aliakbar Movassaghpour Mehdi Talebi Mahdi Abdoli Shadbad Khalil Hajiasgharzadeh Shiva Pourvahdani Behzad Baradaran Source Type: research

Time-dependent changes in striatal monoamine levels and gene expression following single and repeated amphetamine administration in rats
Eur J Pharmacol. 2021 May 4:174148. doi: 10.1016/j.ejphar.2021.174148. Online ahead of print.ABSTRACTAs drug addiction may result from pathological usurpations of learning and memory's neural mechanisms, we focused on the amphetamine-induced time-dependent neurochemical changes associated with neural plasticity. We used juvenile rats as the risk for drug abuse is higher during adolescence. Experiment 1 served to define the appropriate amphetamine dose and the neurochemical effects of a single administration. In experiment 2, rats received seven amphetamine or saline injections in the open-field test throughout a twelve-day...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Andrey Sequeira-Cordero Juan C Brenes Source Type: research

Molecular mechanism of apelin-13 regulation of colonic motility in rats
In conclusion, apelin-13 inhibited the spontaneous contractile activity of isolated rat colons via the suppression of L-type calcium channels and BKCa channels in colonic smooth muscle cells.PMID:33961873 | DOI:10.1016/j.ejphar.2021.174149 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Lin Yan Haixia Ren Fangting Yuan Wenyao Shi Ying Wang Hesheng Luo Source Type: research

ERK1/2 kinases and dopamine D2 receptors participate in the anticonvulsant effects of a new derivative of benzoylpyridine oxime and valproic acid
Eur J Pharmacol. 2021 May 4:174150. doi: 10.1016/j.ejphar.2021.174150. Online ahead of print.ABSTRACTInhibition of the activity of extracellular signal-regulated kinases (ERK1/2) induced by the activation of the dopamine D2 receptor signalling cascade may be a promising pharmacological target. The aim of this work was to study the involvement of ERK1/2 and dopamine D2 receptor in the mechanism of the anticonvulsant action of valproic acid (VA) and a new benzoylpyridine oxime derivative (GIZH-298), which showed antiepileptic activity in different models of epilepsy. We showed that subchronic exposure to maximal electroshock...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Svetlana A Litvinova Tat'yana A Voronina Evgeny A Kondrakhin Igor O Gaydukov Artem I Davletshin Ekaterina V Vasil'eva Georgy I Kovalev David G Garbuz Source Type: research

Metformin protects against neuroinflammation through integrated mechanisms of miR-141 and the NF- ĸB-mediated inflammasome pathway in a diabetic mouse model
Eur J Pharmacol. 2021 May 4:174146. doi: 10.1016/j.ejphar.2021.174146. Online ahead of print.ABSTRACTThe brain responds to diabetic stress by inducing the inflammatory response. Under normal circumstances this process is tightly regulated. However, uncontrolled inflammatory responses lead to compromised function and eventual neurodegeneration. The microRNA (miR)-200 family, specifically miR-141, is differentially expressed in diseased states including cognitive decline, thereby triggering changes in downstream genes. We hypothesised that Metformin (MF) regulates the miR-141/protein phosphatase 2A (PP2A) axis, and associate...
Source: European Journal of Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Authors: Taskeen Fathima Docrat Savania Nagiah Anil A Chuturgoon Source Type: research

SGLT2i increased the plasma fasting glucagon level in patients with diabetes: a meta-analysis
In conclusion, our result indicated SGLT2i intervention would increase the plasma fasting glucagon level in patients with diabetes mellitus. The increase in plasma fasting glucagon level may be associated with reduced insulin level. The increased glucagon-insulin ratio after the use of SGLT2i may make diabetic patients susceptible to ketosis.PMID:33957085 | DOI:10.1016/j.ejphar.2021.174145 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - May 6, 2021 Category: Drugs & Pharmacology Authors: Xingyun Zhu Chu Lin Li Li Suiyuan Hu Xiaoling Cai Linong Ji Source Type: research

Oleic acid and oleoylethanolamide decrease interferon- γ-induced expression of PD-L1 and induce apoptosis in human lung carcinoma cells
This study investigated the effects of oleic acid and an oleic acid metabolite, oleoylethanolamide (OEA), on PD-L1 expression and biomarkers of tumorigenesis in several cancer cell lines, namely A549, HuH-7, MCF-7, DLD-1, and LoVo cells. Specifically, we analyzed the expression of PD-L1 and several apoptosis-related genes using RT-PCR. Interferon-gamma (IFN-γ)-induced modulation of PD-L1 protein expression was investigated using western blotting. Results indicate that IFN-γ stimulation increased the expression of PD-L1 in the chosen cancer cell lines. The IFN-γ-induced expression of PD-L1 was greater in A...
Source: European Journal of Pharmacology - May 6, 2021 Category: Drugs & Pharmacology Authors: Kazuo Yamagata Erika Uzu Yuri Yoshigai Chihiro Kato Motoki Tagami Source Type: research

Therapeutic targets and biological mechanisms of action of curcumin against Zika virus: in silico and in vitro analyses
Eur J Pharmacol. 2021 May 3:174144. doi: 10.1016/j.ejphar.2021.174144. Online ahead of print.ABSTRACTZika virus (ZIKV) is a mosquito-borne flavivirus, that could cause congenital Zika syndrome (CZS), characterized by microcephaly, neurological complications and fetal deaths. No specific treatments for ZIKV are currently available, highlighting the urgent global need to identify and develop therapeutic agents. Drug repositioning of approved natural compounds can provide effective alternative solutions for novel antiviral development. The current study focused on curcumin, a component of turmeric known to exert diverse antiv...
Source: European Journal of Pharmacology - May 6, 2021 Category: Drugs & Pharmacology Authors: Minjee Kim Hanul Choi Young Bong Kim Source Type: research

SGLT2i increased the plasma fasting glucagon level in patients with diabetes: a meta-analysis
In conclusion, our result indicated SGLT2i intervention would increase the plasma fasting glucagon level in patients with diabetes mellitus. The increase in plasma fasting glucagon level may be associated with reduced insulin level. The increased glucagon-insulin ratio after the use of SGLT2i may make diabetic patients susceptible to ketosis.PMID:33957085 | DOI:10.1016/j.ejphar.2021.174145 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - May 6, 2021 Category: Drugs & Pharmacology Authors: Xingyun Zhu Chu Lin Li Li Suiyuan Hu Xiaoling Cai Linong Ji Source Type: research

Oleic acid and oleoylethanolamide decrease interferon- γ-induced expression of PD-L1 and induce apoptosis in human lung carcinoma cells
This study investigated the effects of oleic acid and an oleic acid metabolite, oleoylethanolamide (OEA), on PD-L1 expression and biomarkers of tumorigenesis in several cancer cell lines, namely A549, HuH-7, MCF-7, DLD-1, and LoVo cells. Specifically, we analyzed the expression of PD-L1 and several apoptosis-related genes using RT-PCR. Interferon-gamma (IFN-γ)-induced modulation of PD-L1 protein expression was investigated using western blotting. Results indicate that IFN-γ stimulation increased the expression of PD-L1 in the chosen cancer cell lines. The IFN-γ-induced expression of PD-L1 was greater in A...
Source: European Journal of Pharmacology - May 6, 2021 Category: Drugs & Pharmacology Authors: Kazuo Yamagata Erika Uzu Yuri Yoshigai Chihiro Kato Motoki Tagami Source Type: research

Therapeutic targets and biological mechanisms of action of curcumin against Zika virus: in silico and in vitro analyses
Eur J Pharmacol. 2021 May 3:174144. doi: 10.1016/j.ejphar.2021.174144. Online ahead of print.ABSTRACTZika virus (ZIKV) is a mosquito-borne flavivirus, that could cause congenital Zika syndrome (CZS), characterized by microcephaly, neurological complications and fetal deaths. No specific treatments for ZIKV are currently available, highlighting the urgent global need to identify and develop therapeutic agents. Drug repositioning of approved natural compounds can provide effective alternative solutions for novel antiviral development. The current study focused on curcumin, a component of turmeric known to exert diverse antiv...
Source: European Journal of Pharmacology - May 6, 2021 Category: Drugs & Pharmacology Authors: Minjee Kim Hanul Choi Young Bong Kim Source Type: research

Preconditioning of mesenchymal stem cells with ghrelin exerts superior cardioprotection in aged heart through boosting mitochondrial function and autophagy flux
This study investigated the effects of preconditioning of human umbilical cord-derived MSCs with ghrelin and their combination with nicotinamide-mononucleotide (NMN) on cardioprotection, and the role of autophagy flux and mitochondrial function in aged hearts subjected to IR injury. Aged Sprague Dawley rats (20-22 months old) were subjected to LAD occlusion-induced myocardial IR injury and treated with ghrelin-preconditioned or unconditioned-MSCs at early reperfusion. NMN (500 mg/kg, i.p) was also administered at early reperfusion and repeated 12 h later. Intra-myocardial injection of ghrelin-preconditioned MSCs reduced in...
Source: European Journal of Pharmacology - May 5, 2021 Category: Drugs & Pharmacology Authors: Liqiang Sun Wenlong Zhang Source Type: research

Preconditioning of mesenchymal stem cells with ghrelin exerts superior cardioprotection in aged heart through boosting mitochondrial function and autophagy flux
This study investigated the effects of preconditioning of human umbilical cord-derived MSCs with ghrelin and their combination with nicotinamide-mononucleotide (NMN) on cardioprotection, and the role of autophagy flux and mitochondrial function in aged hearts subjected to IR injury. Aged Sprague Dawley rats (20-22 months old) were subjected to LAD occlusion-induced myocardial IR injury and treated with ghrelin-preconditioned or unconditioned-MSCs at early reperfusion. NMN (500 mg/kg, i.p) was also administered at early reperfusion and repeated 12 h later. Intra-myocardial injection of ghrelin-preconditioned MSCs reduced in...
Source: European Journal of Pharmacology - May 5, 2021 Category: Drugs & Pharmacology Authors: Liqiang Sun Wenlong Zhang Source Type: research

RS4651 suppresses lung fibroblast activation via the TGF- β1/SMAD signalling pathway
CONCLUSIONS: Our data suggest that RS4651 alleviates BLM-induced pulmonary fibrosis in mice by inhibiting the TGF-β1/SMAD signalling pathway.PMID:33940030 | DOI:10.1016/j.ejphar.2021.174135 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - May 3, 2021 Category: Drugs & Pharmacology Authors: Shirong Li Anjian Xu Yanmeng Li Chunting Tan Giuseppe La Regina Romano Silvestri Haoyan Wang Wenjie Qi Source Type: research

Taurine improves follicular survival and function of mice ovarian grafts through increasing CD31 and GDF9 expression and reducing oxidative stress and apoptosis
Eur J Pharmacol. 2021 Apr 30:174134. doi: 10.1016/j.ejphar.2021.174134. Online ahead of print.ABSTRACTIschemia-reperfusion (IR) injury is a major limitation of ovarian transplantation which threatens the follicular and graft survival. Taurine as a potent anti-oxidant, anti-apoptotic and anti-inflammatory agent, can prevent graft damages due to IR. We aimed to investigate the effect of taurine on the follicular survival and function of autotransplanted mouse ovaries. Female mice (4-5 weeks old) were divided into: control, autograft and autograft + taurine (200 mg/kg/day). The level of CD31 expression was evaluated two days ...
Source: European Journal of Pharmacology - May 3, 2021 Category: Drugs & Pharmacology Authors: Sepideh Ahmadi Malek Soleimani Mehranjani Source Type: research

Acteoside exerts neuroprotection effects in the model of Parkinson's disease via inducing autophagy: Network pharmacology and experimental study
In this study, we dissected the neuroprotection effects of ACT on PD and its potential molecular mechanism in our PD model pathology based on network pharmacology prediction and experimental assays. Network pharmacology and bioinformatics analysis demonstrated that ACT has 381 potential targets; among them 78 putative targets associated with PD were closely related to cellular autophagy and apoptotic processes. Our experimental results showed that ACT exerted significant neuroprotection effects on Rotenone (ROT) -induced injury of neuronal cells and Drosophila melanogaster (D. melanogaster). Meanwhile, ACT treatment induce...
Source: European Journal of Pharmacology - May 3, 2021 Category: Drugs & Pharmacology Authors: Mutalifu Aimaiti Ainiwaer Wumaier Yiliyasi Aisa Yu Zhang Xirenayi Xirepu Yilizire Aibaidula XiuYing Lei Qian Chen XueZhao Feng Na Mi Source Type: research