To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Humans ; Adult ; Cigarette Smoking/epidemiology* ; Prevalence ; Electronic Nicotine Delivery Systems ; Tobacco Products ; Republic of Korea/epidemiology*

Objective: This study evaluated the anxiety, work, and socioeconomic burden of emergency physicians (EP) during the coronavirus disease 2019 (COVID-19) pandemic in South Korea. Methods: A cross-sectional observational study was conducted using data from the 2020 Korean Emergency Physician Survey that included the following domains: hospital resources of suspected COVID-19 patients, availability of personal protective equipment, levels of home and workplace anxiety, the severity of work burnout, identification of stressors, changes in personal environments, and measures to decrease stress/anxiety. Results: Totally, 855 eligible participants were enrolled in the study. A statistically significant deterioration was observed in response to decreased working income or an unstable employment situation (0.46±0.88 points). The median number of patients with confirmed COVID-19 was 2.72. The risk of infection during emergency department (ED) work was found to be significantly increased (P<0.01). Of the 751 respondents (91.4%) who reported patient contact during their survey phase, 516 (62.8%) reported having taken the COVID-19 reverse transcription polymerase chain reaction test. The major factors that affected worsening of the work burden were determined to be unsuitable inter-hospital transfer arrangements for febrile patients (3.46±1.06 before vs. 1.99±1.16 after the pandemic, P<0.01) and delayed consultation for patients with fever or respiratory symptoms in the ED (3.20±1.06 before vs. 2.66±1.10 after the pandemic, P<0.01). Conclusion During the peak phase, the COVID-19 pandemic induced substantial workplace and socioeconomic burdens for Korean EPs. The sustained impact of the pandemic on the wellness of EPs deserves further investigation to guide targeted interventions.