Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.