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Papers by mohsen sedighi

Research paper thumbnail of Metabolic disturbance affects postoperative cognitive function in patients undergoing cardiopulmonary bypass

Neurological Sciences, 2021

Objectives Postoperative delirium is a common neuropsychiatric syndrome after coronary artery byp... more Objectives Postoperative delirium is a common neuropsychiatric syndrome after coronary artery bypass grafting (CABG). We aimed to assess and compare clinical outcomes of CABG patients with delirium with a specific focus on the blood biochemical parameters. Methods This investigation was carried out on the 90 eligible patients undergoing CABG. Delirium was measured using the Neecham confusion scale and assessed patients were divided into two groups of delirium (n = 43) and non-delirium (n = 47). Preoperative variables and intraoperative and postoperative outcomes were compared. Results Delirium patients were older (p = 0.003) and had longer intubation time (p = 0.003). Non-delirium patients obtained a significantly higher Neecham confusion score (p = 0.001), and delirium patients experienced a hyperglycemic state at intraoperative (p = 0.004), intubation (p = 0.03), and extubation time (p = 0.02). Lower value of pH was seen at intubation (p = 0.03) and extubation periods (p = 0.001) in delirium group. A significant difference in base excess was observed between two groups at intubation (p = 0.04) and extubation periods (p = 0.004). Potassium level showed a significant decrease in delirium group at intubation (p = 0.01) and extubation periods (p = 0.001). Multivariate regression indicated that aging (OR = 1.08, p = 0.01), narcotic consumption (OR = 3.27, p = 0.05), DM (OR = 3.03, p=0.03), and prolonged intubation (OR = 1.18, p = 0.03) are predictors of delirium. Postoperative hyperglycemia (OR = 1.01, p = 0.002), low pH value (OR = 2.62, p = 0.02), and low potassium level (OR = 3.25, p = 0.03) are associated with development of delirium. Conclusions Postoperative metabolic disturbance and electrolyte imbalances are closely related to the development of delirium after CABG and need to be considered more carefully. Aging, DM, and preoperative use of narcotics are strong predictors of delirium following CABG.

Research paper thumbnail of Linagliptin Protects Human SH-SY5Y Neuroblastoma Cells against Amyloid-β Cytotoxicity via the Activation of Wnt1 and Suppression of IL-6 Release

Iranian Biomedical Journal, 2020

Background: Alzheimer’s disease is one of the neurodegenerative disorders typified by the aggrega... more Background: Alzheimer’s disease is one of the neurodegenerative disorders typified by the aggregate of Aβ and phosphorylated tau protein. Oxidative stress and neuroinflammation, because of Aβ peptides, are strongly involved in the pathophysiology of AD. Linagliptin shows neuroprotective properties against AD pathological processes through alleviation of neural inflammation and AMPK activation. Methods: We assessed the benefits of linagliptin pretreatment (at 10, 20, and 50 nM concentrations), against Aβ1-42 toxicity (20 μM) in SH-SY5Y cells. The concentrations of secreted cytokines, such as TNF-α, IL-6, and IL-1β, and signaling proteins, including pCREB, Wnt1, and PKCε, were quantified by ELISA. Results: We observed that Aβ led to cellular inflammation, which was assessed by measuring inflammatory cytokines (TNF-α, IL-1β, and IL-6). Moreover, Aβ1-42 treatment impaired pCREB, PKCε, and Wnt1 signaling in human SH-SY5Y neuroblastoma cells. Addition of Linagliptin significantly reduced ...

Research paper thumbnail of The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease

Basic and Clinical Neuroscience Journal, 2020

Klotho and Dipeptidyl Peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We... more Klotho and Dipeptidyl Peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer Disease (AD). Methods: This study was conducted on 16 AD patients and 16 healthy age-matched controls. Plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β, interleukin-6 (IL-6), klotho, and DPP4 were measured by enzyme-linked immunosorbent assay. Plasma expression of miR-29a and miR-195 were also measured and compared by a real-time polymerase chain reaction. Results: There was a significant increase in TNF-α (p=0.006), IL-1β (p=0.012), and IL-6 (p=0.012) levels in the AD subjects compared with controls. Also, we found a decrease in plasma levels of klotho and an increase in plasma levels of DPP4 in the AD group that was not significant compared with the controls. Lower expression of miR-29a (P=0.009) and higher expression of miR-195 (P=0.003) were observed in the AD group that was significant than controls. Further analysis showed a negative correlation between klotho and plasma levels of IL-6 (r=-0.58, p=0.01). Also, there was a positive correlation between plasma DPP4 activity and TNF-α levels (r=0.50, P=0.04) and IL-1β (r=0.62, P=0.01). Likewise, plasma klotho concentration showed a negative correlation with the age of AD subjects (r=-0.56, P=0.02). Conclusion: TNF-α, IL-1β, and IL-6 are involved in AD pathophysiology, and dysregulation of DPP4 and klotho may be associated with the inflammatory response of AD. Down-regulation of miR-29a and up-regulation of miR-195 indicated the role of miRNAs in the AD process.

Research paper thumbnail of Early mobilization reduces delirium after coronary artery bypass graft surgery

Asian Cardiovascular and Thoracic Annals, 2020

Background Postoperative delirium is common in patients undergoing coronary artery bypass graftin... more Background Postoperative delirium is common in patients undergoing coronary artery bypass grafting, characterized by cognitive decline. This study aimed to evaluate the effect of early planned mobilization on delirium after coronary artery bypass grafting. Methods This double-blind randomized clinical trial enrolled 92 consecutive patients who underwent coronary artery bypass grafting from September to December 2018. The patients were divided into two groups of 46: a mobilization protocol was applied in the intervention group in the first 2 days after surgery; the control group received routine nursing care only. Demographic data, medical records, and Neecham confusion scores were analyzed. Results Patients in the control group used cigarettes (31.1% vs. 11.1%, p = 0.020) and opium poppy for recreation (35.6% vs. 8.9%, p = 0.002) more frequently, had longer intubation times (11.91 ± 3.87 vs. 10.23 ± 2.71 h, p = 0.020), and fewer blood components infused (15.6% vs. 33.3%, p = 0.05). ...

Research paper thumbnail of Anti-aging Klotho Protects SH-SY5Y Cells Against Amyloid β1–42 Neurotoxicity: Involvement of Wnt1/pCREB/Nrf2/HO-1 Signaling

Journal of Molecular Neuroscience, 2020

Alzheimer's disease (AD) is considered a prevalent neurological disorder with a neurodegenerative... more Alzheimer's disease (AD) is considered a prevalent neurological disorder with a neurodegenerative nature in elderly people. Oxidative stress and neuroinflammation due to amyloid β (Aβ) peptides are strongly involved in AD pathogenesis. Klotho is an anti-aging protein with multiple protective effects that its deficiency is involved in development of age-related disorders. In this study, we investigated the beneficial effect of Klotho pretreatment at different concentrations of 0.5, 1, and 2 nM against Aβ1-42 toxicity at a concentration of 20 μM in human SH-SY5Y neuroblastoma cells. Our findings showed that Klotho could significantly and partially restore cell viability and decrease reactive oxygen species (known as ROS) and improve superoxide dismutase activity (SOD) in addition to reduction of caspase 3 activity and DNA fragmentation following Aβ1-42 challenge. In addition, exogenous Klotho also reduced inflammatory biomarkers consisting of nuclear factor-kB (NF-kB), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in Aβ-exposed cells. Besides, Klotho caused downregulation of Wnt1 level, upregulation of phosphorylated cyclic AMP response element binding (pCREB), and mRNA levels of nuclear factor erythroid 2related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) with no significant alteration of epsilon isoform of protein kinase C (PKCε) after Aβ toxicity. In summary, Klotho could alleviate apoptosis, oxidative stress, and inflammation in human neuroblastoma cells after Aβ challenge and its beneficial effect is partially exerted through appropriate modulation of Wnt1/pCREB/Nrf2/HO-1 signaling.

Research paper thumbnail of Association of circulating klotho and dipeptidyl peptidase-4 activity with inflammatory cytokines in elderly patients with Alzheimer's disease

Research paper thumbnail of Klotho Ameliorates Cellular Inflammation via Suppression of Cytokine Release and Upregulation of miR-29a in the PBMCs of Diagnosed Alzheimer’s Disease Patients

Journal of Molecular Neuroscience, 2019

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by neural in... more Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by neural inflammation and oxidative stress. In the current study, the protective effects of klotho and linagliptin treatment on human peripheral blood mononuclear cells (PBMCs) of AD patients and healthy controls (HCs) are assessed through measurement of inflammatory cytokines, signaling proteins, and miRNA expression. Sixteen diagnosed AD patients and sixteen HCs were enrolled in the study. Blood samples were obtained and PBMCs were isolated. PBMCs were treated with klotho at different concentrations (0.5, 1, and 2 nM) and linagliptin (50 μM). The concentration of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), epsilon isoform of protein kinase C (PKCε), phosphorylated cyclic AMP response element binding (pCREB), and Wnt1 were measured by ELISA. The expression of miR-29a and miR-195 was detected by real-time PCR. The results showed that klotho significantly reduced IL-1β, IL-6, and TNF-α levels in both groups of the experiment. Linagliptin also remarkably reduced TNF-α levels in the AD group. Moreover, klotho caused the downregulation of Wnt1 in the PBMCs of both groups and the upregulation of the pCREB in HCs. Meanwhile, klotho induced miR-29a expression in the PBMCs of HCs, while miR-29a expression was induced in the AD group by klotho and linagliptin. The current findings revealed that klotho alleviates inflammation in human PBMCs, probably through the suppression of inflammatory cytokines and the upregulation of miR-29a, and part of its beneficial effect is mediated through appropriate modulation of the Wnt1/pCREB signaling cascade. In addition, linagliptin exerts protective effects by reducing TNF-α and inducing miR-29a expression in PBMCs.

Research paper thumbnail of Metabolic disturbance affects postoperative cognitive function in patients undergoing cardiopulmonary bypass

Neurological Sciences, 2021

Objectives Postoperative delirium is a common neuropsychiatric syndrome after coronary artery byp... more Objectives Postoperative delirium is a common neuropsychiatric syndrome after coronary artery bypass grafting (CABG). We aimed to assess and compare clinical outcomes of CABG patients with delirium with a specific focus on the blood biochemical parameters. Methods This investigation was carried out on the 90 eligible patients undergoing CABG. Delirium was measured using the Neecham confusion scale and assessed patients were divided into two groups of delirium (n = 43) and non-delirium (n = 47). Preoperative variables and intraoperative and postoperative outcomes were compared. Results Delirium patients were older (p = 0.003) and had longer intubation time (p = 0.003). Non-delirium patients obtained a significantly higher Neecham confusion score (p = 0.001), and delirium patients experienced a hyperglycemic state at intraoperative (p = 0.004), intubation (p = 0.03), and extubation time (p = 0.02). Lower value of pH was seen at intubation (p = 0.03) and extubation periods (p = 0.001) in delirium group. A significant difference in base excess was observed between two groups at intubation (p = 0.04) and extubation periods (p = 0.004). Potassium level showed a significant decrease in delirium group at intubation (p = 0.01) and extubation periods (p = 0.001). Multivariate regression indicated that aging (OR = 1.08, p = 0.01), narcotic consumption (OR = 3.27, p = 0.05), DM (OR = 3.03, p=0.03), and prolonged intubation (OR = 1.18, p = 0.03) are predictors of delirium. Postoperative hyperglycemia (OR = 1.01, p = 0.002), low pH value (OR = 2.62, p = 0.02), and low potassium level (OR = 3.25, p = 0.03) are associated with development of delirium. Conclusions Postoperative metabolic disturbance and electrolyte imbalances are closely related to the development of delirium after CABG and need to be considered more carefully. Aging, DM, and preoperative use of narcotics are strong predictors of delirium following CABG.

Research paper thumbnail of Linagliptin Protects Human SH-SY5Y Neuroblastoma Cells against Amyloid-β Cytotoxicity via the Activation of Wnt1 and Suppression of IL-6 Release

Iranian Biomedical Journal, 2020

Background: Alzheimer’s disease is one of the neurodegenerative disorders typified by the aggrega... more Background: Alzheimer’s disease is one of the neurodegenerative disorders typified by the aggregate of Aβ and phosphorylated tau protein. Oxidative stress and neuroinflammation, because of Aβ peptides, are strongly involved in the pathophysiology of AD. Linagliptin shows neuroprotective properties against AD pathological processes through alleviation of neural inflammation and AMPK activation. Methods: We assessed the benefits of linagliptin pretreatment (at 10, 20, and 50 nM concentrations), against Aβ1-42 toxicity (20 μM) in SH-SY5Y cells. The concentrations of secreted cytokines, such as TNF-α, IL-6, and IL-1β, and signaling proteins, including pCREB, Wnt1, and PKCε, were quantified by ELISA. Results: We observed that Aβ led to cellular inflammation, which was assessed by measuring inflammatory cytokines (TNF-α, IL-1β, and IL-6). Moreover, Aβ1-42 treatment impaired pCREB, PKCε, and Wnt1 signaling in human SH-SY5Y neuroblastoma cells. Addition of Linagliptin significantly reduced ...

Research paper thumbnail of The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease

Basic and Clinical Neuroscience Journal, 2020

Klotho and Dipeptidyl Peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We... more Klotho and Dipeptidyl Peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer Disease (AD). Methods: This study was conducted on 16 AD patients and 16 healthy age-matched controls. Plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β, interleukin-6 (IL-6), klotho, and DPP4 were measured by enzyme-linked immunosorbent assay. Plasma expression of miR-29a and miR-195 were also measured and compared by a real-time polymerase chain reaction. Results: There was a significant increase in TNF-α (p=0.006), IL-1β (p=0.012), and IL-6 (p=0.012) levels in the AD subjects compared with controls. Also, we found a decrease in plasma levels of klotho and an increase in plasma levels of DPP4 in the AD group that was not significant compared with the controls. Lower expression of miR-29a (P=0.009) and higher expression of miR-195 (P=0.003) were observed in the AD group that was significant than controls. Further analysis showed a negative correlation between klotho and plasma levels of IL-6 (r=-0.58, p=0.01). Also, there was a positive correlation between plasma DPP4 activity and TNF-α levels (r=0.50, P=0.04) and IL-1β (r=0.62, P=0.01). Likewise, plasma klotho concentration showed a negative correlation with the age of AD subjects (r=-0.56, P=0.02). Conclusion: TNF-α, IL-1β, and IL-6 are involved in AD pathophysiology, and dysregulation of DPP4 and klotho may be associated with the inflammatory response of AD. Down-regulation of miR-29a and up-regulation of miR-195 indicated the role of miRNAs in the AD process.

Research paper thumbnail of Early mobilization reduces delirium after coronary artery bypass graft surgery

Asian Cardiovascular and Thoracic Annals, 2020

Background Postoperative delirium is common in patients undergoing coronary artery bypass graftin... more Background Postoperative delirium is common in patients undergoing coronary artery bypass grafting, characterized by cognitive decline. This study aimed to evaluate the effect of early planned mobilization on delirium after coronary artery bypass grafting. Methods This double-blind randomized clinical trial enrolled 92 consecutive patients who underwent coronary artery bypass grafting from September to December 2018. The patients were divided into two groups of 46: a mobilization protocol was applied in the intervention group in the first 2 days after surgery; the control group received routine nursing care only. Demographic data, medical records, and Neecham confusion scores were analyzed. Results Patients in the control group used cigarettes (31.1% vs. 11.1%, p = 0.020) and opium poppy for recreation (35.6% vs. 8.9%, p = 0.002) more frequently, had longer intubation times (11.91 ± 3.87 vs. 10.23 ± 2.71 h, p = 0.020), and fewer blood components infused (15.6% vs. 33.3%, p = 0.05). ...

Research paper thumbnail of Anti-aging Klotho Protects SH-SY5Y Cells Against Amyloid β1–42 Neurotoxicity: Involvement of Wnt1/pCREB/Nrf2/HO-1 Signaling

Journal of Molecular Neuroscience, 2020

Alzheimer's disease (AD) is considered a prevalent neurological disorder with a neurodegenerative... more Alzheimer's disease (AD) is considered a prevalent neurological disorder with a neurodegenerative nature in elderly people. Oxidative stress and neuroinflammation due to amyloid β (Aβ) peptides are strongly involved in AD pathogenesis. Klotho is an anti-aging protein with multiple protective effects that its deficiency is involved in development of age-related disorders. In this study, we investigated the beneficial effect of Klotho pretreatment at different concentrations of 0.5, 1, and 2 nM against Aβ1-42 toxicity at a concentration of 20 μM in human SH-SY5Y neuroblastoma cells. Our findings showed that Klotho could significantly and partially restore cell viability and decrease reactive oxygen species (known as ROS) and improve superoxide dismutase activity (SOD) in addition to reduction of caspase 3 activity and DNA fragmentation following Aβ1-42 challenge. In addition, exogenous Klotho also reduced inflammatory biomarkers consisting of nuclear factor-kB (NF-kB), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in Aβ-exposed cells. Besides, Klotho caused downregulation of Wnt1 level, upregulation of phosphorylated cyclic AMP response element binding (pCREB), and mRNA levels of nuclear factor erythroid 2related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) with no significant alteration of epsilon isoform of protein kinase C (PKCε) after Aβ toxicity. In summary, Klotho could alleviate apoptosis, oxidative stress, and inflammation in human neuroblastoma cells after Aβ challenge and its beneficial effect is partially exerted through appropriate modulation of Wnt1/pCREB/Nrf2/HO-1 signaling.

Research paper thumbnail of Association of circulating klotho and dipeptidyl peptidase-4 activity with inflammatory cytokines in elderly patients with Alzheimer's disease

Research paper thumbnail of Klotho Ameliorates Cellular Inflammation via Suppression of Cytokine Release and Upregulation of miR-29a in the PBMCs of Diagnosed Alzheimer’s Disease Patients

Journal of Molecular Neuroscience, 2019

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by neural in... more Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by neural inflammation and oxidative stress. In the current study, the protective effects of klotho and linagliptin treatment on human peripheral blood mononuclear cells (PBMCs) of AD patients and healthy controls (HCs) are assessed through measurement of inflammatory cytokines, signaling proteins, and miRNA expression. Sixteen diagnosed AD patients and sixteen HCs were enrolled in the study. Blood samples were obtained and PBMCs were isolated. PBMCs were treated with klotho at different concentrations (0.5, 1, and 2 nM) and linagliptin (50 μM). The concentration of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), epsilon isoform of protein kinase C (PKCε), phosphorylated cyclic AMP response element binding (pCREB), and Wnt1 were measured by ELISA. The expression of miR-29a and miR-195 was detected by real-time PCR. The results showed that klotho significantly reduced IL-1β, IL-6, and TNF-α levels in both groups of the experiment. Linagliptin also remarkably reduced TNF-α levels in the AD group. Moreover, klotho caused the downregulation of Wnt1 in the PBMCs of both groups and the upregulation of the pCREB in HCs. Meanwhile, klotho induced miR-29a expression in the PBMCs of HCs, while miR-29a expression was induced in the AD group by klotho and linagliptin. The current findings revealed that klotho alleviates inflammation in human PBMCs, probably through the suppression of inflammatory cytokines and the upregulation of miR-29a, and part of its beneficial effect is mediated through appropriate modulation of the Wnt1/pCREB signaling cascade. In addition, linagliptin exerts protective effects by reducing TNF-α and inducing miR-29a expression in PBMCs.