scholarly journals Ticagrelor and clopidogrel suppress NF-κB to treat acute coronary syndrome

2019 ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Acute Coronary Syndrome ◽  
Cell Migration ◽  
Cell Viability ◽  
Umbilical Vein ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background: Inflammatory cytokines are involved in acute coronary syndrome (ACS),and NF-kB is the central regulator of inflammation. Moreover, ticagrelor and clopidogrelcan prevent thrombotic events and improve the care of patients with ACS. Thus, we speculated that ticagrelor and clopidogrel relieve ACS by regulating NF-kB pathway. Methods: After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level changes of molecules in the NF-kB pathway, and the changes in cell viability, apoptosis and the cell cycle, cell migration, vascular formation and other vital activities were detected using quantitative Polymerase chain reaction (qPCR), Western blotting and immunofluorescence assay, CCK8， flow cytometry, transwell assay, matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessedby an unpaired two-tailed t-test. Results: Ticagrelor and clopidogrel can suppress the NF-kB pathway by inhibiting the phosphorylation and entry into the nucleus of p65, restraining the degradation of IKBa, improving cell viability, restoring the cell cycle, cell migration and angiogenic ability, and inhibiting apoptosis. Conclusions: Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-kB signaling to treat acute coronary syndrome.

scholarly journals Ticagrelor and clopidogrel suppress NF-κB signaling pathway to alleviate LPS-induced dysfunction in vein endothelial cells

2019 ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background: Ticagrelor and clopidogrel, P2Y12 receptor antagonists, can prevent thrombotic events and are used to treat cardiovascular diseases such as acute coronary syndrome and chronic obstructive pulmonary disease, in which inflammation is involved. Moreover, NF-kB is the central regulator of inflammation. Thus, we suspected that ticagrelor and clopidogrel are involved in the regulation of the NF-kB signaling pathway.Methods: After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level and subcellular localization of molecules in the NF-kB signaling pathway, cell viability, apoptosis and the cell cycle, cell migration, and vascular formation were detected using quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence assay, CCK8, flow cytometry, transwell assay, and matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessed by an unpaired two-tailed t-test.Results: Ticagrelor and clopidogrel can inhibit the degradation of IKBa and phosphorylation of p65, prevent p65 from entering the nucleus, reduce the production of TNFa, IL-1, IL-8, IL-6 and IL-2, and alleviate the decrease in cell viability, cell migration and angiogenesis, the changes of cell cycle and apoptosis induced by LPS. Conclusions: Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-kB signaling pathway.

scholarly journals Ticagrelor and clopidogrel suppress NF-κB signaling pathway to alleviate LPS-induced dysfunction in vein endothelial cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background Ticagrelor and clopidogrel, P2Y12 receptor antagonists, can prevent thrombotic events and are used to treat cardiovascular diseases such as acute coronary syndrome and chronic obstructive pulmonary disease, in which inflammation is involved. Moreover, NF-B is the central regulator of inflammation. Thus, we suspected that ticagrelor and clopidogrel are involved in the regulation of the NF-ΚB signaling pathway. Methods After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level and subcellular localization of molecules in the NF-ΚB signaling pathway, cell viability, apoptosis and the cell cycle, cell migration, and vascular formation were detected using quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence assay, CCK-8, flow cytometry, transwell assay, and matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessed by an unpaired two-tailed t-test. Results Ticagrelor and clopidogrel can inhibit the degradation of IKBα and phosphorylation of p65, prevent p65 from entering the nucleus, reduce the production of TNFα, IL-1, IL-8, IL-6 and IL-2, and alleviate the decrease in cell viability, cell migration and angiogenesis, the changes of cell cycle and apoptosis induced by LPS. Conclusions Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-ΚB signaling pathway.

scholarly journals Ticagrelor and clopidogrel suppress NF-kB signaling pathway to alleviate LPS-induced dysfunction in vein endothelial cells

2019 ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background: Ticagrelor and clopidogrel, P2Y12 receptor antagonists, can prevent thrombotic events and are used to treat cardiovascular diseases such as acute coronary syndrome and chronic obstructive pulmonary disease, in which inflammation is involved. Moreover, NF-kB is the central regulator of inflammation. Thus, we suspected that ticagrelor and clopidogrel are involved in the regulation of the NF-kB signaling pathway.Methods: After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level and subcellular localization of molecules in the NF-kB signaling pathway, cell viability, apoptosis and the cell cycle, cell migration, and vascular formation were detected using quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence assay, CCK-8, flow cytometry, transwell assay, and matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessed by an unpaired two-tailed t-test.Results: Ticagrelor and clopidogrel can inhibit the degradation of IKBa and phosphorylation of p65, prevent p65 from entering the nucleus, reduce the production of TNFa, IL-1, IL-8, IL-6 and IL-2, and alleviate the decrease in cell viability, cell migration and angiogenesis, the changes of cell cycle and apoptosis induced by LPS.Conclusions: Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-kB signaling pathway.

scholarly journals Quercetin Protects RIMVECs From Inflammatory Damage, Pyroptosis and Cell Migration by Inhibiting the TLR4/NF-κB/NLRP3 Pathway

2021 ◽  
Author(s):  
Huixin Zhang ◽  
Yeye Li ◽  
Zhongjie Liu
Keyword(s):  
Cell Migration ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Quantitative Polymerase Chain Reaction ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Caspase 1 ◽  
Inflammatory Damage

Abstract Background: Intestinal mucosal microvascular endothelial cells (MEC) have multiple functions and play an important role in intestinal bowel diseases (IBD). Quercetin is a flavonoid found in many plants and fruits. It was reported that quercetin can treat several gastrointestinal cancers, but its effect on bacterial enteritis and pyroptosis-related diseases has been rarely studied. This article aims to explore the effect and mechanism of quercetin on inflammatory injury and pyroptosis of RIMVECs.Methods: The inflammatory damage and pyroptosis in RIMVECs were induced by LPS and ATP. Real-time quantitative polymerase chain reaction (RT-qPCR), western blot analysis, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence methods were used to detect TLR4/NF-κB/NLRP3 pathways, inflammatory factors (IL-1β and IL-18) and pyroptosis-related proteins (Caspase-1 and GSDMD). The expression and distribution of ZO-1 were detected by western blot analysis and immunofluorescence method. The late apoptosis and necrosis of cells were measured by cell flow cytometry. Results: The results showed that different concentrations (5, 10, 20μM) of quercetin not only significantly reduced the protein and mRNA levels of TLR4, NLRP3, Caspase-1 and GSDMD, but also down-regulated the protein expression, mRNA and secretion of IL-1β and IL-18. Quercetin also inhibited the phosphorylation of NF-κB p65 and the degradation of IκB. At the same time, quercetin increased the cell migration rate and the expression level of ZO-1, and reduced the number of late apoptotic cells (P<0.05). Conclusions: Our data indicated that Quercetin reduced the inflammatory response and pyroptosis induced by LPS/ATP through the TLR4/NF-κB/NLRP3 pathway, and protected the migration and tight junctions of RIMVECs.

scholarly journals LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 117-127
Author(s):  
Hongmei Gao ◽  
Zhaohui Guo
Keyword(s):  
Smooth Muscle ◽  
Muscle Protein ◽  
Umbilical Vein ◽  
Smooth Muscle Actin ◽  
Quantitative Polymerase Chain Reaction ◽  
Density Lipoprotein ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Lactate Dehydrogenase Activity

Abstract Long noncoding RNAs (lncRNAs) have been verified as vital regulators in human disease, including atherosclerosis. However, the precise role of X-inactive-specific transcript (XIST) in atherosclerosis remains unclear. The proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) exposed to low-density lipoprotein (ox-LDL) were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide, and flow cytometry assays, correspondingly. The western blot assay was used to quantify protein expression. Lactate dehydrogenase activity and the concentrations of inflammatory factors were measured by matched kits. The real-time quantitative polymerase chain reaction (qPCR) was used to determine α-smooth muscle actin, smooth muscle protein 22-α, XIST, miR-98-5p, and pregnancy-associated plasma protein A (PAPPA) levels in HUVECs. The relationship among XIST, miR-98-5p, and PAPPA was analyzed by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. We found ox-LDL repressed proliferation and induced inflammation and apoptosis in HUVECs. Loss-of-functional experiment suggested that the downregulation of XIST overturned the ox-LDL-induced effects on HUVECs. Additionally, overexpression of miR-98-5p-induced effects on ox-LDL-stimulated HUVECs was abolished by upregulation of XIST. However, silencing of miR-98-5p strengthened the ox-LDL-induced effects on HUVECs by increasing expression of PAPPA. Mechanistically, XIST could regulate PAPPA expression in ox-LDL-induced HUVECs by sponging miR-98-5p, providing understanding for atherosclerosis.

scholarly journals Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 465
Author(s):  
Omer Anis ◽  
Ajjampura C. Vinayaka ◽  
Nurit Shalev ◽  
Dvora Namdar ◽  
Stalin Nadarajan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Migration ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
High Performance ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Quantitative Polymerase Chain Reaction ◽  
Migration And Invasion ◽  
Xtt Assay

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.

Evaluation of Serum Level of Interleukin 1 in Patients Suffering from Acute Coronary Syndrome, Admitted to the CCU Ward of AmirAlmomenin Hospital of Zahedan

2021 ◽  
Author(s):  
Hossein Ali Khazaei ◽  
Ahmad Bolouri ◽  
Hony Harati ◽  
Mehdi Mohammadi ◽  
Sayed Mohammad Nasiraldin Tabatabei ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Causes Of Death ◽  
Interleukin 1 ◽  
Developed Countries ◽  
Inflammatory Factors ◽  
Coronary Syndrome ◽  
Common Causes ◽  
Artery Disease ◽  
Flow Blockage ◽  
Q Wave

Background: Atherosclerosis is a disease in which the particles of fat builds up in the blood vessel’s walls. This build up leads to blood flow blockage or can cause the arteries to narrow, but until the stenosis of the vessel is not more than 70 percent, there won’t be any obvious symptoms. Symptoms are dependent on the location of the stenosis that can bring about diseases such as, Unstable Angina (UA), Myocardial Infarction with Q Wave (MIQW) and Non Q Wave (NMIQW). The most common causes of death in most developed countries is Coronary Artery Disease (CAD), and since the inflammatory factors are one of the causes of these diseases, we decided to evaluate the level of the Interleukin-1 (IL-1) in patients with acute coronary syndrome. Methods: 90 patients, suffering from the acute coronary syndrome were selected, which were previously diagnosed and referred to a cardiologist in the Imam Ali Ebneh hospital’s cardiac ward, in 2011. Five ml of periphery blood was obtained from each patient, after 24 hours of hospitalization. Using the ELISA method, the level of interleukin-1 was measured in the three groups of patients, each with symptoms of UA, MIQW and MINQW. Results: Our findings, showed the highest level of interleukin-1 in the MIQW patients, with the average of 46.55 pg/ml and, the lowest level in the MINQW patients, with the average of 28.17 pg/ml. Moreover, the average level of IL-1 in the patient’s serum with UA, is determined equal to 31.28 pg/ml. Although, there was no significant correlations between the type of MI development and UA, there was a significant correlation between the level of IL-1 and the type of MI development. Conclusion: Despite the fact, that the level of IL-1 was higher than normal in all the group types, and no significant correlation between the type of MI development and UA was found, there was statistically a significant correlation between the types of MI development and the level of IL-1.

Effects of oral administration of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine in rat

2020 ◽  
Author(s):  
Xiuling Yang ◽  
Xue Guo ◽  
Li Yanan ◽  
Li Jiaxi ◽  
Liu Yue
Keyword(s):  
Acute Coronary Syndrome ◽  
Plasma Concentration ◽  
Plasma Level ◽  
Adverse Reactions ◽  
Statistical Significance ◽  
Loading Dose ◽  
Time Points ◽  
Coronary Syndrome ◽  
P2y12 Receptor Antagonist ◽  
First Time

Abstract Background: Ticagrelor as a reversible P2Y12 receptor antagonist which plays an important role in the treatment of acute coronary syndrome (ACS). Dyspnea is one of the main adverse reactions of ticagrelor, however the mechanism is not clearly now. The aim of this study was to assess the possible relationship between ticagrelor-related dyspnea and some neurotransmitter in plasma which can contract the bronchial smooth muscle.Methods: The effects of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine was studied in rats. Ticagrelor was administered at a loading dose of 24 mg/kg for the first time, and then maintenance dose 12 mg/kg, twice a day for 6 days. The plasma level of adrenaline, histamine, serotonin, and acetylcholine was determined by LC-MS/MS.Results: The plasma level of serotonin increased after ticagrelor administrating, especially at 1.5h ( p <0.05) reach the level of statistical significance. The level of serotonin in plasma was consistent with ticagrelor blood concentration. Meanwhile, ticagrelor can cause a decrease in the plasma concentration of histamine, and the change was statistically significant at time points of 1.5h, 3.5h and 10.5h respectively. The concentration of the adrenaline and acetylcholine had no change.Conclusions: The results of this study reveal that ticagrelor can increases blood serotonin levels and this may be a cause of dyspnea ticagrelor-related.

A PROSPECTIVE CONSIDERATIONS AND COMPARATIVE EFFICACY BETWEEN IVABRADINE VS BETA BLOCKERS IN SOUTH INDIAN ACUTE CORONARY SYNDROME PATIENTS

2019 ◽  
pp. 193-195
Author(s):  
Hemanth Kumar Lekkala
Keyword(s):  
Heart Rate ◽  
Acute Coronary Syndrome ◽  
Beta Blockers ◽  
Statistical Significance ◽  
Reduced Ejection Fraction ◽  
Coronary Syndrome ◽  
Nyha Classification ◽  
South Indian ◽  
Group A ◽  
Group B

Objectives: the objective of this study was to assess the role of heart rate in acute coronary syndrome with reduced ejection fraction, to assess contraindications for beta blockers, to assess the tolerability between Ivabradine and Beta-Blockers, to assess efficacy between Ivabradine and Beta Blockers, to assess patient condition according to NYHA classification. Methods: A Prospective observational study was conducted for a duration of6 months Study population includes 100 patients in which Group A-50, Group B-50. We were selected the subjects according to inclusion and exclusion criteria. The patients were classified in one of four categories based on their symptoms in regards to normal breathing and varying degrees in shortness of breath by using (The New York Heart Association) NYHA Classification. Results: Majority of the patients were in age group between (55-64)(32%) years of age are highly affected with ACS. Prevalence of ACS is high in Rural (56%). Both drugs decreased the mean heart rate to 89.97±10.27 (Group-A) versus 86.76±13.14 (Group-B) beats per minute (P=0.24). The result obtained are clinically and statistically significant with statistical significance at P>0.05. Conclusion:  In the present study we considered and compared the efficacy between Ivabradine and Beta Blockers in south Indian acute coronary syndrome patients shows Ivabradine is as effective as betablockers in reduction of heart rate.    

scholarly journals LncRNA HOXB-AS3 Promotes Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Gallbladder Cancer Cells by Activating the MEK/ERK Pathway

2022 ◽  
Author(s):  
Jiayan Wu ◽  
Hongquan Zhu ◽  
Jiandong Yu ◽  
Zhiping Chen ◽  
Zeyu Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Migration ◽  
Cell Viability ◽  
Gallbladder Cancer ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Migration Ability ◽  
Mesenchymal Transition

Abstract OBJECTIVE: Long non-coding RNA HOXB-AS3 has been implicated in tumor progression in a variety of carcinomas. However, its biological role in gallbladder cancer (GBC) is unknown. The biological function and underlying mechanism of the lncRNA HOXB-AS3 for GBC were investigated in this study.MATERIALS AND METHODS: To investigate the function of lncRNA HOXB-AS3 in GBC, the level of lncRNA HOXB-AS3 in GBC cells was detected by quantitative reverse-transcription polymerase chain reaction. The cell viability was tested by cell counting kit-8 assay and colony formation assay. Flow cytometry was performed to investigate cell apoptosis and cell cycle. In addition, cell migration ability was assessed by wound healing assay and cell invasion ability by transwell invasion assay. RESULTS: It was found that HOXB-AS3 was obviously elevated in GBC tissues and cells. However, inhibition of HOXB-AS3 could depress NOZ and GBC-SD cell viability as well as induce cell apoptosis. Also, the gallbladder cancer cell cycle was blocked in the G1 phase. Meanwhile, NOZ and GBC-SD cell migration, invasion, and epithelial-mesenchymal transition were obviously suppressed by knockdown of HOXB-AS3. What is more, we found that HOXB-AS3 might promote gallbladder progress by activating the MEK/ERK pathway.CONCLUSION: The results show that lncRNA HOXB-AS3 serves as a key regulator in GBC progression, which provides a new treatment strategy for GBC.

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