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.

Naturally occurring compounds have widely been applied to treat diverse pharmacological effects, including asthma, allergic diseases, antioxidants, inflammation, antibiotics, and cancer. Recent research has revealed the essential role of the thymic stromal lymphopoietin (TSLP) in regulating inflammatory responses at mucosal barriers and maintaining immune homeostasis. Asthma, inflammation, and chronic obstructive pulmonary disease are allergic disorders in which TSLP plays a significant role. Although TSLP’s role in type 2 immune responses has undergone comprehensive investigation, its involvement in inflammatory diseases and cancer has also been found to be expanding. However, investigating how to block the TSLP pathway using natural products has been limited. This paper summarizes the roles of various medicinal plants and their chemical components that effectively inhibit the TSLP pathway. In addition, we also highlight the contributions of several plant-derived compounds to treat allergic diseases via targeting TSLP. This review intends to offer innovative concepts to scientists investigating the use of naturally produced compounds and extracts for the treatment of allergic illnesses.

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.

Naturally occurring compounds have widely been applied to treat diverse pharmacological effects, including asthma, allergic diseases, antioxidants, inflammation, antibiotics, and cancer. Recent research has revealed the essential role of the thymic stromal lymphopoietin (TSLP) in regulating inflammatory responses at mucosal barriers and maintaining immune homeostasis. Asthma, inflammation, and chronic obstructive pulmonary disease are allergic disorders in which TSLP plays a significant role. Although TSLP’s role in type 2 immune responses has undergone comprehensive investigation, its involvement in inflammatory diseases and cancer has also been found to be expanding. However, investigating how to block the TSLP pathway using natural products has been limited. This paper summarizes the roles of various medicinal plants and their chemical components that effectively inhibit the TSLP pathway. In addition, we also highlight the contributions of several plant-derived compounds to treat allergic diseases via targeting TSLP. This review intends to offer innovative concepts to scientists investigating the use of naturally produced compounds and extracts for the treatment of allergic illnesses.

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.

Naturally occurring compounds have widely been applied to treat diverse pharmacological effects, including asthma, allergic diseases, antioxidants, inflammation, antibiotics, and cancer. Recent research has revealed the essential role of the thymic stromal lymphopoietin (TSLP) in regulating inflammatory responses at mucosal barriers and maintaining immune homeostasis. Asthma, inflammation, and chronic obstructive pulmonary disease are allergic disorders in which TSLP plays a significant role. Although TSLP’s role in type 2 immune responses has undergone comprehensive investigation, its involvement in inflammatory diseases and cancer has also been found to be expanding. However, investigating how to block the TSLP pathway using natural products has been limited. This paper summarizes the roles of various medicinal plants and their chemical components that effectively inhibit the TSLP pathway. In addition, we also highlight the contributions of several plant-derived compounds to treat allergic diseases via targeting TSLP. This review intends to offer innovative concepts to scientists investigating the use of naturally produced compounds and extracts for the treatment of allergic illnesses.

Objective: This was a retrospective investigation conducted to evaluate the impact of the coronavirus disease-2019 (COVID-19) pandemic on the treatment and outcomes of patients with ischemic stroke. Methods: Data were collected over one year for the COVID-19 and pre-COVID-19 (control) groups, from May 1, 2020, to April 30, 2021, when COVID-19 was prevalent in Korea, and from May 1, 2018 to April 30, 2019, before the COVID-19 outbreak, respectively. Adult patients diagnosed with acute cerebral infarction at three emergency medical centers during the study period were included. COVID-19-positive patients (i.e., those with COVID-19 symptoms but those who tested positive) were excluded from this study to ensure only the evaluation of delays in stroke treatment due to the pandemic. Results: During the COVID-19 pandemic, of the total of 82,558 patients who visited the emergency centers, 710 were diagnosed with ischemic stroke. The study observed that the pandemic caused process delays for these patients, resulting in longer wait times for brain CT scans (P=0.010, P<0.001) and emergency room stays (P=0.0055, P<0.001) during the COVID-19 period. However, the length of time for administration of tissue plasminogen activator remained relatively constant. Notably, the 28-day mortality rate was considerably higher for patients with COVID-19-related symptoms during the pandemic (13.6% vs 3.1%; P=0.006). A cumulative risk analysis revealed an increased mortality risk for patients with COVID-19 related symptoms (P=0.005). Conclusion This study showed the need to improve emergency care procedures during pandemics to ensure prompt treatment of ischemic stroke. Preparation and resource allocation for ischemic stroke patients with COVID-19 symptoms are crucial.

Objective: This was a retrospective investigation conducted to evaluate the impact of the coronavirus disease-2019 (COVID-19) pandemic on the treatment and outcomes of patients with ischemic stroke. Methods: Data were collected over one year for the COVID-19 and pre-COVID-19 (control) groups, from May 1, 2020, to April 30, 2021, when COVID-19 was prevalent in Korea, and from May 1, 2018 to April 30, 2019, before the COVID-19 outbreak, respectively. Adult patients diagnosed with acute cerebral infarction at three emergency medical centers during the study period were included. COVID-19-positive patients (i.e., those with COVID-19 symptoms but those who tested positive) were excluded from this study to ensure only the evaluation of delays in stroke treatment due to the pandemic. Results: During the COVID-19 pandemic, of the total of 82,558 patients who visited the emergency centers, 710 were diagnosed with ischemic stroke. The study observed that the pandemic caused process delays for these patients, resulting in longer wait times for brain CT scans (P=0.010, P<0.001) and emergency room stays (P=0.0055, P<0.001) during the COVID-19 period. However, the length of time for administration of tissue plasminogen activator remained relatively constant. Notably, the 28-day mortality rate was considerably higher for patients with COVID-19-related symptoms during the pandemic (13.6% vs 3.1%; P=0.006). A cumulative risk analysis revealed an increased mortality risk for patients with COVID-19 related symptoms (P=0.005). Conclusion This study showed the need to improve emergency care procedures during pandemics to ensure prompt treatment of ischemic stroke. Preparation and resource allocation for ischemic stroke patients with COVID-19 symptoms are crucial.

Objective: This was a retrospective investigation conducted to evaluate the impact of the coronavirus disease-2019 (COVID-19) pandemic on the treatment and outcomes of patients with ischemic stroke. Methods: Data were collected over one year for the COVID-19 and pre-COVID-19 (control) groups, from May 1, 2020, to April 30, 2021, when COVID-19 was prevalent in Korea, and from May 1, 2018 to April 30, 2019, before the COVID-19 outbreak, respectively. Adult patients diagnosed with acute cerebral infarction at three emergency medical centers during the study period were included. COVID-19-positive patients (i.e., those with COVID-19 symptoms but those who tested positive) were excluded from this study to ensure only the evaluation of delays in stroke treatment due to the pandemic. Results: During the COVID-19 pandemic, of the total of 82,558 patients who visited the emergency centers, 710 were diagnosed with ischemic stroke. The study observed that the pandemic caused process delays for these patients, resulting in longer wait times for brain CT scans (P=0.010, P<0.001) and emergency room stays (P=0.0055, P<0.001) during the COVID-19 period. However, the length of time for administration of tissue plasminogen activator remained relatively constant. Notably, the 28-day mortality rate was considerably higher for patients with COVID-19-related symptoms during the pandemic (13.6% vs 3.1%; P=0.006). A cumulative risk analysis revealed an increased mortality risk for patients with COVID-19 related symptoms (P=0.005). Conclusion This study showed the need to improve emergency care procedures during pandemics to ensure prompt treatment of ischemic stroke. Preparation and resource allocation for ischemic stroke patients with COVID-19 symptoms are crucial.

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non–small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. Materials and Methods: This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. Results: A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. Conclusion NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.