Objective: To evaluate the effectiveness of a squatting posture grading system established to screen for limited ankle dorsiflexion. Methods: The squat posture grading system categorizes subjects’ squat posture into three grades. Grade 1 is defined as being able to maintain a squatting posture with heels on the ground in full ankle dorsiflexion without effort. Grade 2 is defined as being able to perform the same position, but unable to maintain the position for more than 5 seconds or requiring trunk and leg muscle efforts to maintain the position. Grade 3 is defined as being unable to maintain the same position and falling backwards immediately if attempted to touch the ground with heels. Next, subjects’ ankle dorsiflexion angles were directly measured in knee flexed and extended position by goniometer. Results: Out of the 92 total subjects, 35 were in grade 1, 18 were in grade 2, and 39 were in grade 3. The average ankle dorsiflexion angle with knee flexed position were 23.13° for grade 1, 16.03° for grade 2, and 9.31° for grade 3. The average ankle dorsiflexion angle with knee extended position were 15.16° for grade 1, 7.92° for grade 2, and 3.40° for grade 3. Ankle dorsiflexion angles showed a significant decrease from grade 1 to 3 (p<0.05). Conclusion The squatting posture grading system defined in this study effectively graded the subjects based on the difference in their average ankle dorsiflexion angle. This system could be used as a quick screening method for limited ankle dorsiflexion.

Objective: To evaluate the effectiveness of a squatting posture grading system established to screen for limited ankle dorsiflexion. Methods: The squat posture grading system categorizes subjects’ squat posture into three grades. Grade 1 is defined as being able to maintain a squatting posture with heels on the ground in full ankle dorsiflexion without effort. Grade 2 is defined as being able to perform the same position, but unable to maintain the position for more than 5 seconds or requiring trunk and leg muscle efforts to maintain the position. Grade 3 is defined as being unable to maintain the same position and falling backwards immediately if attempted to touch the ground with heels. Next, subjects’ ankle dorsiflexion angles were directly measured in knee flexed and extended position by goniometer. Results: Out of the 92 total subjects, 35 were in grade 1, 18 were in grade 2, and 39 were in grade 3. The average ankle dorsiflexion angle with knee flexed position were 23.13° for grade 1, 16.03° for grade 2, and 9.31° for grade 3. The average ankle dorsiflexion angle with knee extended position were 15.16° for grade 1, 7.92° for grade 2, and 3.40° for grade 3. Ankle dorsiflexion angles showed a significant decrease from grade 1 to 3 (p<0.05). Conclusion The squatting posture grading system defined in this study effectively graded the subjects based on the difference in their average ankle dorsiflexion angle. This system could be used as a quick screening method for limited ankle dorsiflexion.

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK’s role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.

We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK’s role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.

We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

Objective: To evaluate the effectiveness of a squatting posture grading system established to screen for limited ankle dorsiflexion. Methods: The squat posture grading system categorizes subjects’ squat posture into three grades. Grade 1 is defined as being able to maintain a squatting posture with heels on the ground in full ankle dorsiflexion without effort. Grade 2 is defined as being able to perform the same position, but unable to maintain the position for more than 5 seconds or requiring trunk and leg muscle efforts to maintain the position. Grade 3 is defined as being unable to maintain the same position and falling backwards immediately if attempted to touch the ground with heels. Next, subjects’ ankle dorsiflexion angles were directly measured in knee flexed and extended position by goniometer. Results: Out of the 92 total subjects, 35 were in grade 1, 18 were in grade 2, and 39 were in grade 3. The average ankle dorsiflexion angle with knee flexed position were 23.13° for grade 1, 16.03° for grade 2, and 9.31° for grade 3. The average ankle dorsiflexion angle with knee extended position were 15.16° for grade 1, 7.92° for grade 2, and 3.40° for grade 3. Ankle dorsiflexion angles showed a significant decrease from grade 1 to 3 (p<0.05). Conclusion The squatting posture grading system defined in this study effectively graded the subjects based on the difference in their average ankle dorsiflexion angle. This system could be used as a quick screening method for limited ankle dorsiflexion.

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK’s role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.

We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

Objectives: This study investigated the association between exacerbated economic hardship during the coronavirus disease 2019 (COVID-19) pandemic and changes in the health behaviors of Korean adolescents. Methods: We analyzed data from the 2021 Korea Youth Risk Behavior Survey and included 44 908 students (22 823 boys and 22 085 girls) as study subjects. The dependent variables included changes in health behaviors (breakfast habits, physical activity, and alcohol use) that occurred during the COVID-19 pandemic. The aggravation of economic hardship by COVID-19 and the subjective economic status of the family were used as exposure variables. Multiple logistic regression analysis was utilized to calculate the prevalence odds ratios (PORs). Results: Severe exacerbation of a family’s economic hardship due to COVID-19 was negatively associated with the health behaviors of adolescents, including increased breakfast skipping (POR, 1.85; 95% confidence interval [CI], 1.55 to 2.21 for boys and POR, 1.56; 95% CI, 1.27 to 1.92 for girls) and decreased physical activity (POR, 1.37; 95% CI, 1.19 to 1.57 for boys and POR, 1.38; 95% CI, 1.19 to 1.60 for girls). These negative changes in health behaviors were further amplified when combined with a low subjective family economic status. Conclusions The experience of worsening household hardship can lead to negative changes in health behavior among adolescents. It is crucial to implement measures that address the economic challenges that arise from stressful events such as COVID-19 and to strive to improve the lifestyles of adolescents under such circumstances.