Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, c...Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, cell resources, invasive extraction procedures, immunological rejection, tumorigenesis and ethical challenges make it unlikely that many stem cell types could serve as a practical source for therapy. By contrast, these issues do not pertain to human amnion epithelial cells（h AECs）, which are placenta-derived stem cells. We recently assessed the effects of systemically delivered hAECs on stroke outcome using four animal models of stroke. We demonstrated that when injected intravenously after ischemia onset, hAECs migrate preferentially to the spleen and injured brain to limit apoptosis and inflammation, and attenuate early brain infiltration of immune cells, progression of infarction and systemic immunosuppression and to ultimately ameliorate functional deficits. When administration of hAECs is delayed by 1-3 days poststroke, long-term functional recovery can still be enhanced in young and aged mice of either sex. Moreover, our proof-of-principle findings suggest that h AECs are effective at limiting post-stroke infarct development in non-human primates. Overall, the results suggest that hAECs could be a viable clinical stroke therapy.展开更多
The mineralocorticoid receptor（MR）,well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the las...The mineralocorticoid receptor（MR）,well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the last 10–15 years indicates that MRs are also expressed outside of the kidney,including in the brain,vasculature and heart,where they contribute to the pathophysiology of disease（Dinh et al.,2012;]aisser and Farman, 2016）.展开更多
Objective: To examine the association between a lifetime history of migraines and other headaches with and without aura and Rose angina and coronary heart di sease (CHD). Methods: Participants were 12,409 African Amer...Objective: To examine the association between a lifetime history of migraines and other headaches with and without aura and Rose angina and coronary heart di sease (CHD). Methods: Participants were 12,409 African American and white men an d women from the Atherosclerosis Risk in Communities Study, categorized by their lifetime history of headaches lasting ≥ 4 hours (migraine with aura, migraine without aura, other headaches with aura, other headaches without aura, no headac hes). Gender-specific associations of headaches with Rose angina and CHD, adju sted for sociodemographic and cardiovascular disease risk factors, were evaluate d using Poisson regression. Results: Participants with a history of migraines an d other headaches were more likely to have a history of Rose angina than those w ithout headaches. The associations were stronger for mi graine and other headaches with aura (prevalence ratio [PR] = 3.0, 95% CI = 2.4, 3.7 and PR = 2.0, 95% CI = 1.5, 2.7 for women; PR = 2.2, 95% CI = 1.2, 3.9 and PR = 2.4, 95% CI = 1.4, 3.9 for men) than for migraine and other head aches without aura (PR = 1.5, 95% CI = 1.2, 1.9 and PR = 1.3, 95% CI = 1.1, 1.6 for women; PR = 1.9, 95% CI = 1.2, 2.9 and OR = 1.4, 95% CI = 1.0, 1.8 f or men). In contrast, migraine and other headaches were not associated with CHD, regardless of the presence of aura. Conclusions: The lack of association of mig raines with coronary heart disease suggests that the association of migraine wit h Rose angina is not related to coronary artery disease. Future research assessi ng other common underlying pathologic mechanisms is warranted.展开更多
Dear Editor,Takotsubo syndrome(TS)is a stress-induced non-ischaemic cardiomyopathy that is more common in women,but is associated with higher morbidity and mortality in males.Also known as broken-heart syndrome,TS is ...Dear Editor,Takotsubo syndrome(TS)is a stress-induced non-ischaemic cardiomyopathy that is more common in women,but is associated with higher morbidity and mortality in males.Also known as broken-heart syndrome,TS is characterised by transient left ventricular(LV)dysfunction independent of obstructive coronary artery disease.TS is a polygenic condition and nowhere is this more evident than the use of positive inotropes,such as isoprenaline(ISO)in pre-clinical models.1 There is no standard therapy for broken-heart syndrome because the mechanisms underlying the condition remain unknown.Furthermore,there is no consensus on predisposition for Takotsubo2 and our goal was to better understand the regulatory mechanism as a first step towards improved treatment plans.Suberanilohydroxamic acid or SAHA,a drug approved for cancer treatment by the US Food and Drug Administration has previously been shown to improve cardiopulmonary function.3 We tested the hypothesis that the cardioprotective benefit of SAHA in a pre-clinical model of Takotsubo is conferred by an epigenetic acetylation/deacetylation(Ac/Dc)axis.展开更多
文摘Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, cell resources, invasive extraction procedures, immunological rejection, tumorigenesis and ethical challenges make it unlikely that many stem cell types could serve as a practical source for therapy. By contrast, these issues do not pertain to human amnion epithelial cells（h AECs）, which are placenta-derived stem cells. We recently assessed the effects of systemically delivered hAECs on stroke outcome using four animal models of stroke. We demonstrated that when injected intravenously after ischemia onset, hAECs migrate preferentially to the spleen and injured brain to limit apoptosis and inflammation, and attenuate early brain infiltration of immune cells, progression of infarction and systemic immunosuppression and to ultimately ameliorate functional deficits. When administration of hAECs is delayed by 1-3 days poststroke, long-term functional recovery can still be enhanced in young and aged mice of either sex. Moreover, our proof-of-principle findings suggest that h AECs are effective at limiting post-stroke infarct development in non-human primates. Overall, the results suggest that hAECs could be a viable clinical stroke therapy.
基金supported by a postdoctoral fellowship from the National Health and Medical Research Council (NHMRC) of Australiathe Foundation for High Blood Pressure Research Australia (to SC)grants from the NHMRC and the National Heart Foundation of Australia
文摘The mineralocorticoid receptor（MR）,well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the last 10–15 years indicates that MRs are also expressed outside of the kidney,including in the brain,vasculature and heart,where they contribute to the pathophysiology of disease（Dinh et al.,2012;]aisser and Farman, 2016）.
文摘Objective: To examine the association between a lifetime history of migraines and other headaches with and without aura and Rose angina and coronary heart di sease (CHD). Methods: Participants were 12,409 African American and white men an d women from the Atherosclerosis Risk in Communities Study, categorized by their lifetime history of headaches lasting ≥ 4 hours (migraine with aura, migraine without aura, other headaches with aura, other headaches without aura, no headac hes). Gender-specific associations of headaches with Rose angina and CHD, adju sted for sociodemographic and cardiovascular disease risk factors, were evaluate d using Poisson regression. Results: Participants with a history of migraines an d other headaches were more likely to have a history of Rose angina than those w ithout headaches. The associations were stronger for mi graine and other headaches with aura (prevalence ratio [PR] = 3.0, 95% CI = 2.4, 3.7 and PR = 2.0, 95% CI = 1.5, 2.7 for women; PR = 2.2, 95% CI = 1.2, 3.9 and PR = 2.4, 95% CI = 1.4, 3.9 for men) than for migraine and other head aches without aura (PR = 1.5, 95% CI = 1.2, 1.9 and PR = 1.3, 95% CI = 1.1, 1.6 for women; PR = 1.9, 95% CI = 1.2, 2.9 and OR = 1.4, 95% CI = 1.0, 1.8 f or men). In contrast, migraine and other headaches were not associated with CHD, regardless of the presence of aura. Conclusions: The lack of association of mig raines with coronary heart disease suggests that the association of migraine wit h Rose angina is not related to coronary artery disease. Future research assessi ng other common underlying pathologic mechanisms is warranted.
基金A.E-O.dedicates this article to his late grandmother.Professor Sam El-Osta is a National Health and Medical Research Council(NHMRC)Senior Research Fellow(1154650)Funded by NSFC(81561128017)and NHMRC(1113188)International Joint Programme.
文摘Dear Editor,Takotsubo syndrome(TS)is a stress-induced non-ischaemic cardiomyopathy that is more common in women,but is associated with higher morbidity and mortality in males.Also known as broken-heart syndrome,TS is characterised by transient left ventricular(LV)dysfunction independent of obstructive coronary artery disease.TS is a polygenic condition and nowhere is this more evident than the use of positive inotropes,such as isoprenaline(ISO)in pre-clinical models.1 There is no standard therapy for broken-heart syndrome because the mechanisms underlying the condition remain unknown.Furthermore,there is no consensus on predisposition for Takotsubo2 and our goal was to better understand the regulatory mechanism as a first step towards improved treatment plans.Suberanilohydroxamic acid or SAHA,a drug approved for cancer treatment by the US Food and Drug Administration has previously been shown to improve cardiopulmonary function.3 We tested the hypothesis that the cardioprotective benefit of SAHA in a pre-clinical model of Takotsubo is conferred by an epigenetic acetylation/deacetylation(Ac/Dc)axis.
