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.

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.

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.

Background: This study investigated trends in national expenditures on anticancer and immunomodulating agents from 2013 to 2022. Methods: Information was obtained from the National Health Insurance claims data spanning a period of 10 years, from 2013 to 2022. The subjects of this study are patients diagnosed with cancer who used anticancer agents between January 1, 2013, and December 31, 2022. Trends were examined across various categories, including sex, age groups, routes of healthcare use, and types of healthcare institutions. We calculated the compound annual growth rate in both the number of patients and expenditures by year. Results: In 2013, pharmaceutical expenditures amounted to USD 11,984 million, representing 25.5% of the total healthcare expenditures, which were USD 46,984 million.Within this pharmaceutical expenditure, anticancer medications constituted USD 584 million, or 4.9%. By 2022, pharmaceutical expenditures had risen to USD 22,093 million, accounting for 22.8% of the total healthcare expenditures of USD 96,904 million. Of this amount, USD 1,566 million was allocated to anticancer drugs, which represented 7.1% of the total pharmaceutical expenditures. Between 2013 and 2022, total healthcare expenditures experienced a significant increase of 106.2%, reaching USD 49,920 million. Concurrently, pharmaceutical expenditures rose by 91.1% to USD 10,919 million, while expenditures on anticancer drugs surged by 168.2% to USD 982 million. In 2022, the category with the highest expenditures was ATC L01FF, which includes programmed cell death protein 1/death ligand 1 inhibitors such as nivolumab, totaling USD 266.2 million. This was followed by L01FD at USD 198.8 million and L01EA at USD 140.4 million. Since 2018, however, spending on immune checkpoint blockers targeting cell death proteins or ligands has continued to rise and currently ranks first. Conclusion The number of patients using anticancer drugs and the associated drug expenditures have risen between 2013 and 2022. As the share of anticancer drugs in total drug expenditures grows, so too do the overall expenditures. This escalating financial burden highlights the necessity for policymakers to thoroughly understand the appropriate and costeffective usage of anticancer drugs, as it directly influences the affordability and accessibility of healthcare services.

Background: This study investigated trends in national expenditures on anticancer and immunomodulating agents from 2013 to 2022. Methods: Information was obtained from the National Health Insurance claims data spanning a period of 10 years, from 2013 to 2022. The subjects of this study are patients diagnosed with cancer who used anticancer agents between January 1, 2013, and December 31, 2022. Trends were examined across various categories, including sex, age groups, routes of healthcare use, and types of healthcare institutions. We calculated the compound annual growth rate in both the number of patients and expenditures by year. Results: In 2013, pharmaceutical expenditures amounted to USD 11,984 million, representing 25.5% of the total healthcare expenditures, which were USD 46,984 million.Within this pharmaceutical expenditure, anticancer medications constituted USD 584 million, or 4.9%. By 2022, pharmaceutical expenditures had risen to USD 22,093 million, accounting for 22.8% of the total healthcare expenditures of USD 96,904 million. Of this amount, USD 1,566 million was allocated to anticancer drugs, which represented 7.1% of the total pharmaceutical expenditures. Between 2013 and 2022, total healthcare expenditures experienced a significant increase of 106.2%, reaching USD 49,920 million. Concurrently, pharmaceutical expenditures rose by 91.1% to USD 10,919 million, while expenditures on anticancer drugs surged by 168.2% to USD 982 million. In 2022, the category with the highest expenditures was ATC L01FF, which includes programmed cell death protein 1/death ligand 1 inhibitors such as nivolumab, totaling USD 266.2 million. This was followed by L01FD at USD 198.8 million and L01EA at USD 140.4 million. Since 2018, however, spending on immune checkpoint blockers targeting cell death proteins or ligands has continued to rise and currently ranks first. Conclusion The number of patients using anticancer drugs and the associated drug expenditures have risen between 2013 and 2022. As the share of anticancer drugs in total drug expenditures grows, so too do the overall expenditures. This escalating financial burden highlights the necessity for policymakers to thoroughly understand the appropriate and costeffective usage of anticancer drugs, as it directly influences the affordability and accessibility of healthcare services.

Background: This study investigated trends in national expenditures on anticancer and immunomodulating agents from 2013 to 2022. Methods: Information was obtained from the National Health Insurance claims data spanning a period of 10 years, from 2013 to 2022. The subjects of this study are patients diagnosed with cancer who used anticancer agents between January 1, 2013, and December 31, 2022. Trends were examined across various categories, including sex, age groups, routes of healthcare use, and types of healthcare institutions. We calculated the compound annual growth rate in both the number of patients and expenditures by year. Results: In 2013, pharmaceutical expenditures amounted to USD 11,984 million, representing 25.5% of the total healthcare expenditures, which were USD 46,984 million.Within this pharmaceutical expenditure, anticancer medications constituted USD 584 million, or 4.9%. By 2022, pharmaceutical expenditures had risen to USD 22,093 million, accounting for 22.8% of the total healthcare expenditures of USD 96,904 million. Of this amount, USD 1,566 million was allocated to anticancer drugs, which represented 7.1% of the total pharmaceutical expenditures. Between 2013 and 2022, total healthcare expenditures experienced a significant increase of 106.2%, reaching USD 49,920 million. Concurrently, pharmaceutical expenditures rose by 91.1% to USD 10,919 million, while expenditures on anticancer drugs surged by 168.2% to USD 982 million. In 2022, the category with the highest expenditures was ATC L01FF, which includes programmed cell death protein 1/death ligand 1 inhibitors such as nivolumab, totaling USD 266.2 million. This was followed by L01FD at USD 198.8 million and L01EA at USD 140.4 million. Since 2018, however, spending on immune checkpoint blockers targeting cell death proteins or ligands has continued to rise and currently ranks first. Conclusion The number of patients using anticancer drugs and the associated drug expenditures have risen between 2013 and 2022. As the share of anticancer drugs in total drug expenditures grows, so too do the overall expenditures. This escalating financial burden highlights the necessity for policymakers to thoroughly understand the appropriate and costeffective usage of anticancer drugs, as it directly influences the affordability and accessibility of healthcare services.

Background: This study investigated trends in national expenditures on anticancer and immunomodulating agents from 2013 to 2022. Methods: Information was obtained from the National Health Insurance claims data spanning a period of 10 years, from 2013 to 2022. The subjects of this study are patients diagnosed with cancer who used anticancer agents between January 1, 2013, and December 31, 2022. Trends were examined across various categories, including sex, age groups, routes of healthcare use, and types of healthcare institutions. We calculated the compound annual growth rate in both the number of patients and expenditures by year. Results: In 2013, pharmaceutical expenditures amounted to USD 11,984 million, representing 25.5% of the total healthcare expenditures, which were USD 46,984 million.Within this pharmaceutical expenditure, anticancer medications constituted USD 584 million, or 4.9%. By 2022, pharmaceutical expenditures had risen to USD 22,093 million, accounting for 22.8% of the total healthcare expenditures of USD 96,904 million. Of this amount, USD 1,566 million was allocated to anticancer drugs, which represented 7.1% of the total pharmaceutical expenditures. Between 2013 and 2022, total healthcare expenditures experienced a significant increase of 106.2%, reaching USD 49,920 million. Concurrently, pharmaceutical expenditures rose by 91.1% to USD 10,919 million, while expenditures on anticancer drugs surged by 168.2% to USD 982 million. In 2022, the category with the highest expenditures was ATC L01FF, which includes programmed cell death protein 1/death ligand 1 inhibitors such as nivolumab, totaling USD 266.2 million. This was followed by L01FD at USD 198.8 million and L01EA at USD 140.4 million. Since 2018, however, spending on immune checkpoint blockers targeting cell death proteins or ligands has continued to rise and currently ranks first. Conclusion The number of patients using anticancer drugs and the associated drug expenditures have risen between 2013 and 2022. As the share of anticancer drugs in total drug expenditures grows, so too do the overall expenditures. This escalating financial burden highlights the necessity for policymakers to thoroughly understand the appropriate and costeffective usage of anticancer drugs, as it directly influences the affordability and accessibility of healthcare services.

Background: Spinal anesthesia-induced hypotension (SAH) frequently occurs in older patients, many of whom have mild left ventricular (LV) diastolic dysfunction, often asymptomatic at rest. This study investigated the association between preoperative echocardiographic measurements and SAH in older patients with mild LV diastolic dysfunction. Methods: We conducted a retrospective observational study using data from electronic medical records. The patients ≥ 65 years old who underwent spinal anesthesia for urologic surgery between January 2016 and December 2017 and whose preoperative echocardiography within 6 months before surgery revealed grade I LV diastolic dysfunction were recruited. SAH was investigated using the anesthesia records. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: A total of 163 patients were analyzed. SAH and significant SAH developed in 55 (33.7%) patients. The mitral inflow E velocity was an independent risk factor for SAH (odds ratio [OR], 0.886; 95% confidence interval [CI], 0.845–0.929; P < 0.001). The area under the ROC curve for mitral inflow E velocity to predict SAH was 0.819 (95% CI, 0.752–0.875; P < 0.001). If mitral inflow E velocity was ≤ 60 cm/s, SAH was predicted with a sensitivity of 83.6% and specificity of 70.4%. Conclusions The preoperative mitral inflow E velocity demonstrated the greatest predictability of SAH in older patients with mild LV diastolic dysfunction. This may assist in identifying patients at high risk of SAH and guiding preventive strategies in the future.

BACKGROUND/OBJECTIVES: The umami taste receptor (TAS1R1/TAS1R3) is endogenously expressed in skeletal muscle and is involved in myogenesis; however, there is a lack of evidence about whether the expression of the umami taste receptor is involved in muscular diseases. This study aimed to elucidate the effects of the umami taste receptor and its mechanism on muscle wasting in cancer cachexia using in vivo and in vitro models.MATERIALS/METHODS: The Lewis lung carcinoma-induced cancer cachexia model was used in vivo and in vitro, and the expressions of umami taste receptor and muscle atrophy-related markers, muscle atrophy F-box protein, and muscle RING-finger protein-1 were analyzed. RESULTS: Results showed that TAS1R1 was significantly downregulated in vivo and in vitro under the muscle wasting condition. Moreover, overexpression of TAS1R1 in vitro in the human primary cell model protected the cells from muscle atrophy, and knockdown of TAS1R1 using siRNA exacerbated muscle atrophy. CONCLUSION Taken together, the umami taste receptor exerts protective effects on muscle-wasting conditions by restoring dysregulated muscle atrophy in cancer cachexia. In conclusion, this result provided evidence that the umami taste receptor exerts a therapeutic anti-cancer cachexia effect by restoring muscle atrophy.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA. METHODS: We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model. RESULTS: IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration. CONCLUSION These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.