Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the bloo...Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.展开更多
The aim of this study was to identify the correlation between stress, lifestyle, and hyperglycemia among middle-aged Japanese male workers. We also analyzed the obese (OB) and non-obese (non- OB) groups pertaining to ...The aim of this study was to identify the correlation between stress, lifestyle, and hyperglycemia among middle-aged Japanese male workers. We also analyzed the obese (OB) and non-obese (non- OB) groups pertaining to the risk of hyperglycemia. A total of 353 male employees aged between 50 and 59 years taking health checkup sat a company in Japan were examined. The data were collected using validated scales of occupational stress and medical examination. Of the 353 employees, 335 (effective response rate 95%) were analyzed. “Support from colleagues” and “reward from work” reported by the OB group were lower than the non-OB group. The items “eating until satiety” and “having greasy meal often” were significantly more common in the OB group than in the non-OB group. There was a significant correlation between less sleep time and hyperglycemia in the OB group than in the non-OB group. The non-OB group reported more overtime hours than the OB group. Hyperglycemia in the non-OB group was positively correlated with long working hours, “workload,” and “mental workload.” The results indicated that the OB group would benefit from lifestyle interventions, for example, improvement in sleep time and eating habits may prevent hyperglycemia and eventually in obesity. Furthermore, it was suggested that stress in response to “workload” and “mental workload” owing to long working hours leads to hyperglycemia in the non-OB group. Therefore, the improvement of the workplace environment, reducing the number of hours at work, and stress management are required to prevent hyperglycemia in the non-OB group.展开更多
Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for compr...Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for comprehensive approaches addressing the complex pathophysiology of diabetes complications.The recent study by Attia et al explores the potential of a novel therapy combining metformin with cholecalciferol(vitamin D3)and taurine to mitigate T2DM-related complications in a rat model.The findings indicate that this treatment combination improves glycemic control and reduces oxidative stress,inflammation,and lipid abnormalities.However,the study is limited by a lack of safety profile data and in-depth molecular mechanism insights.This editorial critically highlights the study's strengths and weaknesses,compares it against other combination therapy research in T2DM,and underscores the need to explore further the mechanisms underpinning the observed therapeutic effects and investigate the safety profile of this novel approach.展开更多
Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serio...Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serious but common diseases and their association with atherosclerotic cardiovascular risk factors establish a vicious circle culminating in high atherogenicity.Because of that,it is of paramount importance to perform risk stratification of patients with prediabetes to define phenotypes that benefit from various interventions.Furthermore,stress hyperglycemia assessment of hospitalized patients and consensus on the definition of prediabetes is vital.The roles lifestyle and metformin play in prediabetes are well established.However,the role of glucagon-like peptide agonists and metabolic surgery is less clear.Prediabetes is considered an intermediate between normoglycemia and diabetes along the blood glucose continuum.One billion people are expected to suffer from prediabetes by the year 2045.Therefore,realworld randomized controlled trials to assess major adverse cardiac or cerebrovascular event risk reduction and reversal/prevention of type 2 diabetes among patients are needed to determine the proper interventions.展开更多
Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective ...Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective in increasing superoxide dismutase activity. This study sought to investigate the neuroprotective effect of puerarin on high glucose-induced oxidative stress and Schwann cell apoptosis in vitro. Intracellular reactive oxygen radicals and mitochondrial transmembrane potential were detected by flow cytometry analysis. Apoptosis was confirmed by TUNEL and oxidative stress was monitored using an enzyme-linked immunosorbent assay for the DNA marker 8-hydroxy-2-deoxyguanosine. The expression levels of bax and bcl-2 were analyzed by quantitative real-time reverse transcriptase-PCR, while protein expression of cleaved caspase-3 and -9 were analyzed by means of western blotting. Results suggested that puerarin treatment inhibited high glucose-induced oxidative stress, mitochondrial depolarization and apoptosis in a dose-dependent manner. Furthermore, puerarin treatment downregulated Bax expression, upregulated bcl-2 expression and attenuated the activation of caspase-3 and -9. Overall, our results indicated that puerarin antagonized high glucose-induced oxidative stress and apoptosis in Schwann cells.展开更多
Hyperglycemia has been identified as one of the important factors involved in the microvascular complications of diabetes, and has been related to increased cardiovascular mortality. Endothelial damage and dysfunction...Hyperglycemia has been identified as one of the important factors involved in the microvascular complications of diabetes, and has been related to increased cardiovascular mortality. Endothelial damage and dysfunction result from diabetes; therefore, the aim of this study was to determine the response of endothelial cells to stressful stimuli, modelled in normal and high glucose concentrations in vitro. EAhy 926 endothelial ceils were cultured in 5 mmol/L or 30 mmol/L glucose conditions for a 24 hour period and oxidative stress was induced by exposure to hydrogen peroxide （HzO2） or tumour necrosis factor- α （TNF- α ）, following which the protective effect of the glucocorticoid dexamethasone was assessed. Apoptosis, necrosis and cell viability were determined using an ELISA for DNA fragmentation, an enzymatic lactate dehydrogenase assay and an MTT assay, respectively. High glucose significantly increased the susceptibility of EAhy 926 cells to apoptosis in the presence of 500 gmol/L H2O2 , above that induced in normal glucose （P〈0.02）. A reduction of H2O2- and TNF- a -induced apoptosis occurred in both high and low glucose after treatment with dexamethasone （P〈0.05）. Conclusion high glucose is effective in significantly augmenting stress caused by H2O2, but not in causing stress alone. These findings suggest a mechanism by which short term hyperglycemia may facilitate and augment endothelial damage.展开更多
基金supported by the Ningbo Public Welfare Science and Technology Program,No.2022S023(to JY)Ningbo Natural Science Foundation,No.2022J211(to JS)+2 种基金Ningbo Medical and Health Brand Discipline,No.PPXK2018-04(to XG)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.
文摘The aim of this study was to identify the correlation between stress, lifestyle, and hyperglycemia among middle-aged Japanese male workers. We also analyzed the obese (OB) and non-obese (non- OB) groups pertaining to the risk of hyperglycemia. A total of 353 male employees aged between 50 and 59 years taking health checkup sat a company in Japan were examined. The data were collected using validated scales of occupational stress and medical examination. Of the 353 employees, 335 (effective response rate 95%) were analyzed. “Support from colleagues” and “reward from work” reported by the OB group were lower than the non-OB group. The items “eating until satiety” and “having greasy meal often” were significantly more common in the OB group than in the non-OB group. There was a significant correlation between less sleep time and hyperglycemia in the OB group than in the non-OB group. The non-OB group reported more overtime hours than the OB group. Hyperglycemia in the non-OB group was positively correlated with long working hours, “workload,” and “mental workload.” The results indicated that the OB group would benefit from lifestyle interventions, for example, improvement in sleep time and eating habits may prevent hyperglycemia and eventually in obesity. Furthermore, it was suggested that stress in response to “workload” and “mental workload” owing to long working hours leads to hyperglycemia in the non-OB group. Therefore, the improvement of the workplace environment, reducing the number of hours at work, and stress management are required to prevent hyperglycemia in the non-OB group.
文摘Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for comprehensive approaches addressing the complex pathophysiology of diabetes complications.The recent study by Attia et al explores the potential of a novel therapy combining metformin with cholecalciferol(vitamin D3)and taurine to mitigate T2DM-related complications in a rat model.The findings indicate that this treatment combination improves glycemic control and reduces oxidative stress,inflammation,and lipid abnormalities.However,the study is limited by a lack of safety profile data and in-depth molecular mechanism insights.This editorial critically highlights the study's strengths and weaknesses,compares it against other combination therapy research in T2DM,and underscores the need to explore further the mechanisms underpinning the observed therapeutic effects and investigate the safety profile of this novel approach.
文摘Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serious but common diseases and their association with atherosclerotic cardiovascular risk factors establish a vicious circle culminating in high atherogenicity.Because of that,it is of paramount importance to perform risk stratification of patients with prediabetes to define phenotypes that benefit from various interventions.Furthermore,stress hyperglycemia assessment of hospitalized patients and consensus on the definition of prediabetes is vital.The roles lifestyle and metformin play in prediabetes are well established.However,the role of glucagon-like peptide agonists and metabolic surgery is less clear.Prediabetes is considered an intermediate between normoglycemia and diabetes along the blood glucose continuum.One billion people are expected to suffer from prediabetes by the year 2045.Therefore,realworld randomized controlled trials to assess major adverse cardiac or cerebrovascular event risk reduction and reversal/prevention of type 2 diabetes among patients are needed to determine the proper interventions.
基金supported by the National Natural Science Foundation of China, No. 30973354
文摘Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective in increasing superoxide dismutase activity. This study sought to investigate the neuroprotective effect of puerarin on high glucose-induced oxidative stress and Schwann cell apoptosis in vitro. Intracellular reactive oxygen radicals and mitochondrial transmembrane potential were detected by flow cytometry analysis. Apoptosis was confirmed by TUNEL and oxidative stress was monitored using an enzyme-linked immunosorbent assay for the DNA marker 8-hydroxy-2-deoxyguanosine. The expression levels of bax and bcl-2 were analyzed by quantitative real-time reverse transcriptase-PCR, while protein expression of cleaved caspase-3 and -9 were analyzed by means of western blotting. Results suggested that puerarin treatment inhibited high glucose-induced oxidative stress, mitochondrial depolarization and apoptosis in a dose-dependent manner. Furthermore, puerarin treatment downregulated Bax expression, upregulated bcl-2 expression and attenuated the activation of caspase-3 and -9. Overall, our results indicated that puerarin antagonized high glucose-induced oxidative stress and apoptosis in Schwann cells.
文摘Hyperglycemia has been identified as one of the important factors involved in the microvascular complications of diabetes, and has been related to increased cardiovascular mortality. Endothelial damage and dysfunction result from diabetes; therefore, the aim of this study was to determine the response of endothelial cells to stressful stimuli, modelled in normal and high glucose concentrations in vitro. EAhy 926 endothelial ceils were cultured in 5 mmol/L or 30 mmol/L glucose conditions for a 24 hour period and oxidative stress was induced by exposure to hydrogen peroxide （HzO2） or tumour necrosis factor- α （TNF- α ）, following which the protective effect of the glucocorticoid dexamethasone was assessed. Apoptosis, necrosis and cell viability were determined using an ELISA for DNA fragmentation, an enzymatic lactate dehydrogenase assay and an MTT assay, respectively. High glucose significantly increased the susceptibility of EAhy 926 cells to apoptosis in the presence of 500 gmol/L H2O2 , above that induced in normal glucose （P〈0.02）. A reduction of H2O2- and TNF- a -induced apoptosis occurred in both high and low glucose after treatment with dexamethasone （P〈0.05）. Conclusion high glucose is effective in significantly augmenting stress caused by H2O2, but not in causing stress alone. These findings suggest a mechanism by which short term hyperglycemia may facilitate and augment endothelial damage.
