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Background. In the present study, we aimed to find out whether luteolin (Lut) pretreatment could ameliorate myocardial ischemia/reperfusion (I/R) injury by regulating the lncRNA just proximal to XIST (JPX)/microRNA-146b (miR-146b) axis. Methods. We established the models in vitro (HL-1 cells) and in vivo (C57BL/6J mice) to certify the protection mechanism of Lut pretreatment on myocardial I/R injury. Dual luciferase reporter gene assay was utilized for validating that JPX could bind to miR-146b. JPX and miR-146b expression levels were determined by RT-qPCR. Western blot was utilized to examine apoptosis-related protein expression levels, including cleaved caspase-9, caspase-9, cleaved caspase-3, caspase-3, Bcl-2, Bax, and BAG-1. Apoptosis was analyzed by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, as well as flow cytometry. Animal echocardiography was used to measure cardiac function (ejection fraction (EF) and fractional shortening (FS) indicators). Results. miR-146b was demonstrated to bind and recognize the JPX sequence site by dual luciferase reporter gene assay. The expression level of miR-146b was corroborated to be enhanced by H/R using RT-qPCR (P < 0.001 vs. Con). Moreover, JPX could reduce the expression of miR-146b, whereas inhibiting JPX could reverse the alteration (P < 0.001 vs. H/R, respectively). Western blot analysis demonstrated that Lut pretreatment increased BAG-1 expression level and Bcl-2/Bax ratio, but diminished the ratio of cleaved caspase 9/caspase 9 and cleaved caspase 3/caspase 3 (P < 0.001 vs. H/R, respectively). Moreover, the cell apoptosis change trend, measured by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, along with flow cytometry, was consistent with that of apoptosis-related proteins. Furthermore, pretreatment with Lut improved cardiac function (EF and FS) (P < 0.001 vs. I/R, respectively), as indicated in animal echocardiography. Conclusion. Our results demonstrated that in vitro and in vivo, Lut pretreatment inhibited apoptosis via the JPX/miR-146b axis, ultimately improving myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Our aim was to examine clinical trials, provide guidance to practitioners and estimate the efficacy and safety of two agents by comparing low dose ticagrelor with standard dose clopidogrel in patients with acute coronary syndrome. We systematically looked through Pubmed, Embase, the Cochrane Library, Wanfang data and CNKI for trials comparing low dose ticagrelor with standard dose clopidogrel for the treatment of patients with ACS since the database was created. The primary endpoint for efficacy was the rate of major adverse cardiac events (MACEs). The primary endpoint for safety was the rate of major bleeding events. We also evaluated platelet function between low dose ticagrelor and standard dose clopidogrel in ACS patients. From 6744 articles, 16 studies including 1629 patients met the inclusion criteria. In contrast with standard dose clopidogrel, low dose ticagrelor significantly reduced MACEs (OR 0.39, 95% CI 0.26, 0.58) and the difference was statistically significant (p<0.01). No difference was noted for major bleeding events (OR 1.16, 95% CI 0.43, 3.08) between the two agents (p=0.77). In addition, low dose ticagrelor showed lower platelet aggregation rate than clopidogrel (standardised mean difference (SMD) -0.68, 95% CI -0.83 to 0.53) (p<0.01). Platelet reaction units for low dose ticagrelor were much lower than those for standard dose clopidogrel (SMD -2.46, 95% CI -2.85 to -2.07) (p<0.01). In comparison with standard dose clopidogrel, low dose ticagrelor significantly lowered the incidence of MACEs, improved left ventricular ejection fraction, decreased left ventricular end diastolic dimension and did not expand the risk of major bleeding events or minor or minimal bleeding events in ACS patients with a considerable safety and efficacy profile. In addition, low dose ticagrelor was associated with dramatically lower platelet aggregation compared with standard dose clopidogrel. [ABSTRACT FROM AUTHOR]

Background/Aims: A major challenge for current therapeutic strategies against ischemia/ reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. Methods: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R. The phosphorylation of p38 and phospholamban (p-PLB), the levels and activity of SERCA2a and the levels of proteins related to apoptosis were measured. Apoptotic cells were assessed using the TUNEL assay. Single-cell shortening, Ca2+ transients, and the decay of the mitochondrial membrane potential (Δψm) were detected. Results: The p38 MAPK pathway was activated during the I/R process, and inhibiting it with SB203580 promoted p-PLB, which enhanced the activity of SERCA2a and relieved the calcium overload to promote the recovery of the Δψm and reduce cardiomyocyte apoptosis in I/R. Luteolin also suppressed the activation of the p38 MAPK pathway and showed cardioprotective effects during I/R injury. Conclusions: We conclude that luteolin enhances SERCA2a activity to improve systolic/diastolic function during I/R in rat hearts and cardiomyocytes by attenuating the inhibitive effects of the p38 pathway on p-PLB. [ABSTRACT FROM AUTHOR]

The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications. [ABSTRACT FROM AUTHOR]

Background: In the present study, we aimed to find out whether luteolin (Lut) pretreatment could ameliorate myocardial ischemia/reperfusion (I/R) injury by regulating the lncRNA just proximal to XIST (JPX)/microRNA-146b (miR-146b) axis., Methods: We established the models in vitro (HL-1 cells) and in vivo (C57BL/6J mice) to certify the protection mechanism of Lut pretreatment on myocardial I/R injury. Dual luciferase reporter gene assay was utilized for validating that JPX could bind to miR-146b. JPX and miR-146b expression levels were determined by RT-qPCR. Western blot was utilized to examine apoptosis-related protein expression levels, including cleaved caspase-9, caspase-9, cleaved caspase-3, caspase-3, Bcl-2, Bax, and BAG-1. Apoptosis was analyzed by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, as well as flow cytometry. Animal echocardiography was used to measure cardiac function (ejection fraction (EF) and fractional shortening (FS) indicators)., Results: miR-146b was demonstrated to bind and recognize the JPX sequence site by dual luciferase reporter gene assay. The expression level of miR-146b was corroborated to be enhanced by H/R using RT-qPCR ( P < 0.001 vs. Con). Moreover, JPX could reduce the expression of miR-146b, whereas inhibiting JPX could reverse the alteration ( P < 0.001 vs. H/R, respectively). Western blot analysis demonstrated that Lut pretreatment increased BAG-1 expression level and Bcl-2/Bax ratio, but diminished the ratio of cleaved caspase 9/caspase 9 and cleaved caspase 3/caspase 3 ( P < 0.001 vs. H/R, respectively). Moreover, the cell apoptosis change trend, measured by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, along with flow cytometry, was consistent with that of apoptosis-related proteins. Furthermore, pretreatment with Lut improved cardiac function (EF and FS) ( P < 0.001 vs. I/R, respectively), as indicated in animal echocardiography., Conclusion: Our results demonstrated that in vitro and in vivo , Lut pretreatment inhibited apoptosis via the JPX/miR-146b axis, ultimately improving myocardial I/R injury., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Tongda Xu et al.)