Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reper...Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.展开更多
This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani,which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for metabolic dysfunction-associat...This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani,which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for metabolic dysfunction-associated fatty liver disease.We provide supplementary insights to their research,highlighting the broader systemic implications of GLP-1RAs,synthesizing the current understanding of their mechanisms and the trajectory of research in this field.GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond.Beyond glycemic control,GLP-1RAs demonstrate cardiovascular and renal protective effects,offering potential in managing diabetic kidney disease alongside renin–angiotensin–aldosterone system inhibitors.Their role in bone metabolism hints at benefits for diabetic osteoporosis,while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling.Additionally,they improve hormonal and metabolic profiles in polycystic ovary syndrome.This editorial highlights the multifaceted mechanisms of GLP-1RAs,emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.展开更多
BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal fu...BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well described.AIM To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.METHODS This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,2021.Patients were classified based on whether they received PGE1.PGE1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative period.Demographics,post-LT treatments and/or complications,renal function,and survival were analyzed.Multivariable logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically significant.RESULTS A total of 145 patients underwent LT,with 44(30%)receiving PGE1.Baseline patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between the two groups(95.4%vs 93.9%,P=0.74 and 88.4%vs 86.9%,P=0.81 respectively).Although the PGE1 group had a significantly lower glomerular filtration rate(eGFR)on post-LT day 7(46.3 mL/minute±26.7 mL/minute vs 62.5 mL/minute±34 mL/minute,P=0.009),the eventual need for renal replacement therapy(13.6%vs 5.9%,P=0.09),the number of dialysis sessions(0.91 vs 0.27,P=0.13),and eGFR at 1-month(37.2 mL/minute±35.9 mL/minute vs 42 mL/minute±36.9 mL/minute,P=0.49),6-months(54.8 mL/minute±21.6 mL/minute vs 62 mL/minute±21.4 mL/minute,P=0.09),and 12-months(63.7 mL/minute±20.7 mL/minute vs 62.8 mL/minute±20.3 mL/minute,P=0.85)post-LT were similar to those in the non-PGE1 group.CONCLUSION In patients who received PGE1 for ischemia-reperfusion injury,despite immediate acute renal injury post-LT,the renal function at 1-month,6-months,and 12-months post-LT was similar compared to those without ischemiareperfusion injury.Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.展开更多
To clarify the characteristics of photoinhibition and the primary defense mechanisms of ephemeral plant leaves against photodestruction under high temperature stress,inhibitors and the technology to determine chloroph...To clarify the characteristics of photoinhibition and the primary defense mechanisms of ephemeral plant leaves against photodestruction under high temperature stress,inhibitors and the technology to determine chlorophyll fluorescence were used to explore the protective effects of D1 protein turnover and the lutein cycle in the high temperature stress of the leaves of three ephemeral plants.The results showed that the maximum light conversion efficiency(Fv/Fm)of the ephemeral plant leaves decreased,and the initial fluorescence(Fo)increased under 35℃±1℃ heat stress for 1-4 h or on sunny days in the summer.Both Fv/Fm and Fo could be recovered after 8 h of darkness or afternoon weakening of the external temperature.Streptomycin sulfate(SM)or dithiothreitol(DTT)accelerated the decrease of Fv/Fm and the photochemical quenching coefficient(qP)in the leaves of three ephemeral plants at high temperature,and the decrease was greater in the SM than in the DTT treatment.When the high temperature stress was prolonged,the Y(II)values of light energy distribution parameters of PSII decreased,and the Y(NPQ)and Y(NO)values increased gradually in all the treatment groups of the three ephemeral plants.The results showed that the leaves of the three ephemeral plants had their own highly advanced mechanisms to protect against photodamage,which inhibited the turnover of D1 protein and xanthophyll cycle.This can damage the PSII reaction center in the leaves of the three ephemeral plants under high temperature.The protective effect of D1 protein turnover on heat stress in Erodium oxyrrhynchum and Senecio subdentatus was greater than that of the lutein cycle,while the protective effect of lutein cycle was greater than that of D1 protein turnover in Heliotropium acutiflorum subjected to heat damage.展开更多
Glucagon-like peptide-1(GLP-1)is a multifunctional hormone with broad pharmacological potential to control inflammation,protect cardiovascular,kidney,and liver functions.Moreover,GLP-1 can also cross the blood-brain b...Glucagon-like peptide-1(GLP-1)is a multifunctional hormone with broad pharmacological potential to control inflammation,protect cardiovascular,kidney,and liver functions.Moreover,GLP-1 can also cross the blood-brain barrier and bind with GLP-1R distributed in various parts of the brain,thereby reducing apoptosis caused by neuroinflammation and oxygen stress,and promoting learning,memory,cognitive function,neuroprotection,and nerve cell remodeling.However,the exact molecular pathway by which GLP-1 receptor agonists(GLP-1RAs)exerts protective effects on many organs is not fully understood,so it is a hot topic of research.In this article,the recent research on the multi-organ protection of GLP-1 is reviewed,with emphasis on the research progress in the field of nervous system and perioperative anesthesia.展开更多
The regulatory mechanisms of cytoplasmic Ca2＋ after myocardial infarction-induced Ca2＋ overload involve secretory pathway Ca2＋-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi ...The regulatory mechanisms of cytoplasmic Ca2＋ after myocardial infarction-induced Ca2＋ overload involve secretory pathway Ca2＋-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi apparatus on Ca2＋ overload after cerebral ischemia and reperfusion remains unclear. Four-vessel occlusion rats were used as animal models of cerebral ischemia. The expression of secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus was detected by immunoblotting, and Ca2＋ concentrations in the cytoplasm and Golgi vesicles were determined. Results showed an overload of cytoplasmic Ca2＋ during ischemia and reperfusion that reached a peak after reperfusion. Levels of Golgi Ca2＋ showed an opposite effect. The expression of Golgi-specific secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion, and increased after reperfusion for 6 hours. This variation was similar to the alteration of calcium in separated Golgi vesicles. These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload, and that secretory pathway Ca2＋-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells. Thus, we concluded that secretory pathway Ca2＋-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress, responding to cerebral ischemia and reperfusion. The secretory pathway Ca2＋-ATPase 1 can be an important neuroprotective target of ischemic stroke.展开更多
基金supported fiancially by the Natural Science Foundation of Inner Mongolia Autonomous Region in China(Grant No.2018MS08043)Inner Mongolia Autonomous Region Scientific and Technological Achievements Transformation Guidance Project in China(2020PT0030).
文摘Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.
基金Supported by National Natural Science Foundation of China,No.U23A20398 and No.82030007Sichuan Science and Technology Program,No.2022YFS0578.
文摘This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani,which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for metabolic dysfunction-associated fatty liver disease.We provide supplementary insights to their research,highlighting the broader systemic implications of GLP-1RAs,synthesizing the current understanding of their mechanisms and the trajectory of research in this field.GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond.Beyond glycemic control,GLP-1RAs demonstrate cardiovascular and renal protective effects,offering potential in managing diabetic kidney disease alongside renin–angiotensin–aldosterone system inhibitors.Their role in bone metabolism hints at benefits for diabetic osteoporosis,while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling.Additionally,they improve hormonal and metabolic profiles in polycystic ovary syndrome.This editorial highlights the multifaceted mechanisms of GLP-1RAs,emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.
文摘BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well described.AIM To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.METHODS This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,2021.Patients were classified based on whether they received PGE1.PGE1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative period.Demographics,post-LT treatments and/or complications,renal function,and survival were analyzed.Multivariable logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically significant.RESULTS A total of 145 patients underwent LT,with 44(30%)receiving PGE1.Baseline patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between the two groups(95.4%vs 93.9%,P=0.74 and 88.4%vs 86.9%,P=0.81 respectively).Although the PGE1 group had a significantly lower glomerular filtration rate(eGFR)on post-LT day 7(46.3 mL/minute±26.7 mL/minute vs 62.5 mL/minute±34 mL/minute,P=0.009),the eventual need for renal replacement therapy(13.6%vs 5.9%,P=0.09),the number of dialysis sessions(0.91 vs 0.27,P=0.13),and eGFR at 1-month(37.2 mL/minute±35.9 mL/minute vs 42 mL/minute±36.9 mL/minute,P=0.49),6-months(54.8 mL/minute±21.6 mL/minute vs 62 mL/minute±21.4 mL/minute,P=0.09),and 12-months(63.7 mL/minute±20.7 mL/minute vs 62.8 mL/minute±20.3 mL/minute,P=0.85)post-LT were similar to those in the non-PGE1 group.CONCLUSION In patients who received PGE1 for ischemia-reperfusion injury,despite immediate acute renal injury post-LT,the renal function at 1-month,6-months,and 12-months post-LT was similar compared to those without ischemiareperfusion injury.Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.
基金This work was supported by the Open Foundation of the State Key Laboratory of Desert and Oasis Ecology(KH0054).
文摘To clarify the characteristics of photoinhibition and the primary defense mechanisms of ephemeral plant leaves against photodestruction under high temperature stress,inhibitors and the technology to determine chlorophyll fluorescence were used to explore the protective effects of D1 protein turnover and the lutein cycle in the high temperature stress of the leaves of three ephemeral plants.The results showed that the maximum light conversion efficiency(Fv/Fm)of the ephemeral plant leaves decreased,and the initial fluorescence(Fo)increased under 35℃±1℃ heat stress for 1-4 h or on sunny days in the summer.Both Fv/Fm and Fo could be recovered after 8 h of darkness or afternoon weakening of the external temperature.Streptomycin sulfate(SM)or dithiothreitol(DTT)accelerated the decrease of Fv/Fm and the photochemical quenching coefficient(qP)in the leaves of three ephemeral plants at high temperature,and the decrease was greater in the SM than in the DTT treatment.When the high temperature stress was prolonged,the Y(II)values of light energy distribution parameters of PSII decreased,and the Y(NPQ)and Y(NO)values increased gradually in all the treatment groups of the three ephemeral plants.The results showed that the leaves of the three ephemeral plants had their own highly advanced mechanisms to protect against photodamage,which inhibited the turnover of D1 protein and xanthophyll cycle.This can damage the PSII reaction center in the leaves of the three ephemeral plants under high temperature.The protective effect of D1 protein turnover on heat stress in Erodium oxyrrhynchum and Senecio subdentatus was greater than that of the lutein cycle,while the protective effect of lutein cycle was greater than that of D1 protein turnover in Heliotropium acutiflorum subjected to heat damage.
基金Shanxi Youth Science and Technology Research Foundation(2019041035-3).
文摘Glucagon-like peptide-1(GLP-1)is a multifunctional hormone with broad pharmacological potential to control inflammation,protect cardiovascular,kidney,and liver functions.Moreover,GLP-1 can also cross the blood-brain barrier and bind with GLP-1R distributed in various parts of the brain,thereby reducing apoptosis caused by neuroinflammation and oxygen stress,and promoting learning,memory,cognitive function,neuroprotection,and nerve cell remodeling.However,the exact molecular pathway by which GLP-1 receptor agonists(GLP-1RAs)exerts protective effects on many organs is not fully understood,so it is a hot topic of research.In this article,the recent research on the multi-organ protection of GLP-1 is reviewed,with emphasis on the research progress in the field of nervous system and perioperative anesthesia.
基金supported by the National Natural Science Foundation of China,No.81171239
文摘The regulatory mechanisms of cytoplasmic Ca2＋ after myocardial infarction-induced Ca2＋ overload involve secretory pathway Ca2＋-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi apparatus on Ca2＋ overload after cerebral ischemia and reperfusion remains unclear. Four-vessel occlusion rats were used as animal models of cerebral ischemia. The expression of secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus was detected by immunoblotting, and Ca2＋ concentrations in the cytoplasm and Golgi vesicles were determined. Results showed an overload of cytoplasmic Ca2＋ during ischemia and reperfusion that reached a peak after reperfusion. Levels of Golgi Ca2＋ showed an opposite effect. The expression of Golgi-specific secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion, and increased after reperfusion for 6 hours. This variation was similar to the alteration of calcium in separated Golgi vesicles. These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload, and that secretory pathway Ca2＋-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells. Thus, we concluded that secretory pathway Ca2＋-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress, responding to cerebral ischemia and reperfusion. The secretory pathway Ca2＋-ATPase 1 can be an important neuroprotective target of ischemic stroke.
