Summary:Dexmedetomidine(DEX),a potent and highly selective agonist for a2-adrenergic receptors(a2AR),exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca^2+influx.However,the exact action...Summary:Dexmedetomidine(DEX),a potent and highly selective agonist for a2-adrenergic receptors(a2AR),exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca^2+influx.However,the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation(OGD/R)injury in vitro are unknown.We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells,as evidenced by decreased oxidative stress,autophagy,and neuronal apoptosis.Specifically,DEX pretreatment decreased the expression levels of stromal interaction molecule 1(STIM1)and calcium release-activated calcium channel protein 1(Orail),and reduced the concentration of intracellular calcium pools.In addition,variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions,which were modulated through STIM 1/Orail signaling.Moreover,DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3(LC3),hallmark markers of autophagy,and the formation of autophagosomes.In conclusion,these results suggested that DEX exerts neuroprotective effects against oxidative stress,autophagy,and neuronal apoptosis afier OGD/R injury via modulation of Caf-STIM1/Orai1 signaling.Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.展开更多
BACKGROUND We studied the protective effects of Qingyi decoction(QYD)(a Traditional Chinese Medicine)against severe acute pancreatitis(SAP)-induced myocardial infarction(MI).AIM To study the function and mechanism of ...BACKGROUND We studied the protective effects of Qingyi decoction(QYD)(a Traditional Chinese Medicine)against severe acute pancreatitis(SAP)-induced myocardial infarction(MI).AIM To study the function and mechanism of QYD in the treatment of myocardial injuries induced by SAP.METHODS Ultrasonic cardiography,hematoxylin and eosin staining,immunohistochemistry,qRT-PCR,western blot,enzyme-linked immunosorbent assays,and apoptosis staining techniques were used to determine the effects of QYD following SAP-induced MI in Sprague-Dawley rats.RESULTS Our SAP model showed severe myocardial histological abnormalities and marked differences in the symptoms,mortality rate,and ultrasonic cardiography outputs among the different groups compared to the control.The expression of serum cytokines[interleukin(IL)-1?,IL-6,IL-8,IL-12,amyloidβ,and tumor necrosis factor-α]were significantly higher in the SAP versus QYD treated group(P<0.05 for all).STIM1 and Orai1 expression in myocardial tissue extracts were significantly decreased post QYD gavage(P<0.001).There was no significant histological difference between the 2-aminoethyl diphenylborinate inhibitor and QYD groups.The SAP group had a significantly higher apoptosis index score compared to the QYD group(P<0.001).CONCLUSION QYD conferred cardio-protection against SAP-induced MI by regulating myocardial-associated protein expression(STIM1 and Orai1).展开更多
Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryoni...Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China(No.81801175 and No.81970722)the Fundamental Research Funds for the Central Universities(No.WK9110000044 and No.WK9110000036)+2 种基金China Scholarship Council(No.201706270155)the China Postdoctoral Science Foundation(No.2019M662179)the Anhui Province Postdoctoral Science Foundation(No.2019B324).
文摘Summary:Dexmedetomidine(DEX),a potent and highly selective agonist for a2-adrenergic receptors(a2AR),exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca^2+influx.However,the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation(OGD/R)injury in vitro are unknown.We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells,as evidenced by decreased oxidative stress,autophagy,and neuronal apoptosis.Specifically,DEX pretreatment decreased the expression levels of stromal interaction molecule 1(STIM1)and calcium release-activated calcium channel protein 1(Orail),and reduced the concentration of intracellular calcium pools.In addition,variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions,which were modulated through STIM 1/Orail signaling.Moreover,DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3(LC3),hallmark markers of autophagy,and the formation of autophagosomes.In conclusion,these results suggested that DEX exerts neuroprotective effects against oxidative stress,autophagy,and neuronal apoptosis afier OGD/R injury via modulation of Caf-STIM1/Orai1 signaling.Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.
基金the National Natural Science Foundation of China,No,81573751.
文摘BACKGROUND We studied the protective effects of Qingyi decoction(QYD)(a Traditional Chinese Medicine)against severe acute pancreatitis(SAP)-induced myocardial infarction(MI).AIM To study the function and mechanism of QYD in the treatment of myocardial injuries induced by SAP.METHODS Ultrasonic cardiography,hematoxylin and eosin staining,immunohistochemistry,qRT-PCR,western blot,enzyme-linked immunosorbent assays,and apoptosis staining techniques were used to determine the effects of QYD following SAP-induced MI in Sprague-Dawley rats.RESULTS Our SAP model showed severe myocardial histological abnormalities and marked differences in the symptoms,mortality rate,and ultrasonic cardiography outputs among the different groups compared to the control.The expression of serum cytokines[interleukin(IL)-1?,IL-6,IL-8,IL-12,amyloidβ,and tumor necrosis factor-α]were significantly higher in the SAP versus QYD treated group(P<0.05 for all).STIM1 and Orai1 expression in myocardial tissue extracts were significantly decreased post QYD gavage(P<0.001).There was no significant histological difference between the 2-aminoethyl diphenylborinate inhibitor and QYD groups.The SAP group had a significantly higher apoptosis index score compared to the QYD group(P<0.001).CONCLUSION QYD conferred cardio-protection against SAP-induced MI by regulating myocardial-associated protein expression(STIM1 and Orai1).
基金National Institute of Dental&Craniofacial Research,No.1R21DE028265-01A1.
文摘Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.
