BACKGROUND/OBJECTIVES: Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging.MATERIALS/METHODS: The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS: Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.

BACKGROUND: Beta-carotene (BC) is a carotenoid which exerts anti-cancer effects in several types of cancer, including colorectal cancer. Epigenetic modifications of genes, such as histone deacetylation and DNA hypermethylation, have also been detected in various types of cancer. To understand the molecular mechanism underlying cancer preventive and therapeutic effects of BC, microRNAs (miRNAs), histone acetylation, and global DNA methylation in colon cancer stem cells (CSCs) were investigated.METHODS: HCT116 colon cancer cells positive for expression of CD44 and CD133 were sorted by flow cytometry and used in subsequent experiments. Cell proliferation was examined by the MTT assay and self-renewal capacity was analyzed by the sphere formation assay. The miRNA sequencing array was used to detect miRNAs regulated by BC. Histone acetylation levels were measured by the Western blot analysis. mRNA expression of DNA methyltransferases (DNMTs) was examined by qPCR and global DNA methylation levels were determined by enzyme-linked immunosorbent assay.RESULTS: Treatment of CD44⁺CD133⁺ colon CSCs with BC caused a reduction in both cell proliferation and sphere formation. Analysis of the miRNA sequencing array showed that BC regulated expression of miRNAs associated with histone acetylation. Histone H3 and H4 acetylation levels were elevated by BC treatment. In addition, BC treatment down-regulated DNMT3A mRNA expression and global DNA methylation in colon CSCs.CONCLUSIONS: These results suggest that BC regulates epigenetic modifications for its anti-cancer effects in colon CSCs.
Acetylation ; beta Carotene ; Blotting, Western ; Cell Proliferation ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; DNA Methylation ; DNA ; Enzyme-Linked Immunosorbent Assay ; Epigenomics ; Flow Cytometry ; Histones ; Methyltransferases ; MicroRNAs ; RNA, Messenger ; Stem Cells ; Therapeutic Uses

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.

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.

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/OBJECTIVES: Brain senescence causes cognitive impairment and neurodegeneration. It has also been demonstrated that curcumin (Cur) and hesperetin (Hes), both antioxidant polyphenolic compounds, mediate anti-aging and neuroprotective effects. Therefore, the objective of this study was to investigate whether Cur, Hes, and/or their combination exert anti-aging effects in D-galactose (Dg)-induced aged neuronal cells and rats.MATERIALS/METHODS: SH-SY5Y cells differentiated in response to retinoic acid were treated with Cur (1 μM), Hes (1 μM), or a combination of both, followed by 300 mM Dg.Neuronal loss was subsequently evaluated by measuring average neurite length and analyzing expression of β-tubulin III, phosphorylated extracellular signal-regulated kinases, and neurofilament heavy polypeptide. Cellular senescence and related proteins, p16 and p21, were also investigated, including their regulation of antioxidant enzymes. In vivo, brain aging was induced by injecting 250 mg/kg body weight (b.w.) Dg. The effects of supplementing this model with 50 mg/kg b.w. Cur, 50 mg/kg b.w. Hes, or a combination of both for 3 months were subsequently evaluated. Brain aging was examined with a step-through passive avoidance test and apoptosis markers were analyzed in brain cortex tissues. RESULTS: Cur, Hes, and their combination improved neuron length and cellular senescence by decreasing the number of β-gal stained cells, down-regulated expression of p16 and p21, and up-regulated expression of antioxidant enzymes, including superoxide dismutase 1, glutathione peroxidase 1, and catalase. Administration of Cur, Hes, or their combination also tended to ameliorate cognitive impairment and suppress apoptosis in the cerebral cortex by downregulating Bax and poly (ADP-ribose) polymerase expression and increasing Bcl-2 expression. CONCLUSIONS Cur and Hes appear to attenuate Dg-induced brain aging via regulation of antioxidant enzymes and apoptosis. These results suggest that Cur and Hes may mediate neuroprotective effects in the aging process, and further study of these antioxidant polyphenolic compounds is warranted.