There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.
Adenosine Triphosphatases* ; Adenosine Triphosphate ; Binding Sites ; Cell Proliferation ; DNA Topoisomerases, Type II* ; Heat-Shock Proteins* ; Histidine ; Hot Temperature* ; Humans ; Phosphotransferases

BACKGROUND/OBJECTIVES: Curcumin, an active ingredient in turmeric, is highly consumed in South Asia. However, curry that contains turmeric as its main spice might be the major source of curcumin in most other countries. Although curcumin consumption is not as high in these countries as South Asia, the regular consumption of curcumin may provide a significant health-beneficial effect. This study evaluated whether the moderate consumption of curry can affect blood glucose and lipid levels that become dysregulated with age. SUBJECTS/METHODS: This study used data obtained from the Korea National Health and Nutrition Examination Survey, conducted from 2012 to 2013, to assess curry consumption frequency as well as blood glucose and blood lipid levels. The levels of blood glucose and lipids were subdivided by age, sex, and body mass index, and compared according to the curry consumption level. The estimates in each subgroup were further adjusted for potential confounding factors, including the diagnosis of diseases, physical activity, and smoking. RESULTS: After adjusting for the above confounding factors, the blood glucose and triglyceride levels were significantly lower in the moderate curry consumption group compared to the low curry consumption group, both in older (> 45) male and younger (30 to 44) female overweight individuals who have high blood glucose and triglyceride levels. CONCLUSIONS: These results suggest that curcumin consumption, in an ordinary diet, can have health-beneficial effects, including being helpful in maintaining blood glucose and triglyceride levels that become dysregulated with age. The results should be further confirmed in future studies.
Asia ; Blood Glucose ; Body Mass Index ; Curcuma ; Curcumin ; Diagnosis ; Diet ; Female ; Glucose* ; Humans ; Korea ; Male ; Motor Activity ; Nutrition Surveys ; Overweight ; Smoke ; Smoking ; Spices ; Triglycerides

BACKGROUND/OBJECTIVES: Turmeric and its active component curcumin have received considerable attention due to their many recognized biological activities. Turmeric has been commonly used in food preparation and herbal remedies in South Asia, leading to a high consumption rate of curcumin in this region. However, the amount of curcumin in the Korean diet has not yet been estimated, where turmeric is not a common ingredient. SUBJECTS/METHODS: This study utilized the combined data sets obtained from the Korea National Health and Nutrition Examination Survey conducted from 2008 to 2012 in order to estimate the curcumin intake in the Korean diet. The mean intake of curcumin was estimated from the amount of curcumin-containing foods (curry powder and ready-made curry) consumed using reported curcumin content in commercial turmeric and curry powders. RESULTS: Only 0.06% of Koreans responded that they consumed foods containing curcumin in a given day, and 40% of them were younger than 20 years of age. Curcumin-containing foods were largely prepared at home (72.9%) and a significant proportion (20.4%, nearly twice that of all other foods) was consumed as school and workplace meals. The estimated mean turmeric intake was about 0.47 g/day corresponding to 2.7-14.8 mg curcumin, while the average curry powder consumption was about 16.4 g, which gave rise to curcumin intake in the range of 8.2-95.0 mg among individuals who consumed curcumin. The difference in estimated curcumin intake by using the curcumin content in curry powder and turmeric may reflect that curry powder manufactured in Korea might contain higher amounts of other ingredients such as flour, and an estimation based on the curcumin content in the turmeric might be more acceptable. CONCLUSIONS: Thus, the amount of curcumin that can be obtained from the Korean diet in a day is 2.7-14.8 mg, corresponding to nearly one fourth of the daily curcumin intake in South Asia, although curcumin is rarely consumed in Korea.
Asia ; Curcuma ; Curcumin* ; Dataset ; Diet ; Flour ; Humans ; Korea ; Meals ; Nutrition Surveys* ; Powders

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: The efficacy of the long-pulsed diode laser (LPDL) in hair removal is determined with various physical parameters. Recently, LPDLs with a larger spot size are commercially available; however, the independent effect of spot size on hair removal has not been studied. OBJECTIVE: This study aimed to compare the efficacy of the LPDL in hair removal depending on the spot size. METHODS: A randomized, evaluators-blind, intrapatient comparison (left vs. right) trial was designed. Ten healthy Korean women received three hair removal treatment sessions on both armpits with the 805-nm LPDL and followed for 3 months. A 10x10 mm handpiece (D1) or a 10x30 mm handpiece (D3) was randomly assigned to the right or left axilla. The fluence, pulse duration, and epidermal cooling temperature were identical for both armpits. Hair clearance was quantified with high-resolution photos taken at each visit. Postprocedural pain was quantified on a visual analogue scale. Adverse events were evaluated by physical examination and the patients' self-report. RESULTS: The mean hair clearance at 3 months after three treatment sessions was 38.7% and 50.1% on the armpits treated with D1 and D3, respectively (p=0.028). Procedural pain was significantly greater in the side treated with D3 (p=0.009). Serious adverse events were not observed. CONCLUSION: Given that the pulse duration, fluence, and epidermal cooling were identical, the 805-nm LPDL at the three times larger spot size showed an efficacy improvement of 29.5% in axillary hair removal without serious adverse events.
Axilla ; Female ; Hair Removal* ; Hair* ; Humans ; Lasers, Semiconductor* ; Physical Examination

BACKGROUND: The efficacy of the long-pulsed diode laser (LPDL) in hair removal is determined with various physical parameters. Recently, LPDLs with a larger spot size are commercially available; however, the independent effect of spot size on hair removal has not been studied. OBJECTIVE: This study aimed to compare the efficacy of the LPDL in hair removal depending on the spot size. METHODS: A randomized, evaluators-blind, intrapatient comparison (left vs. right) trial was designed. Ten healthy Korean women received three hair removal treatment sessions on both armpits with the 805-nm LPDL and followed for 3 months. A 10x10 mm handpiece (D1) or a 10x30 mm handpiece (D3) was randomly assigned to the right or left axilla. The fluence, pulse duration, and epidermal cooling temperature were identical for both armpits. Hair clearance was quantified with high-resolution photos taken at each visit. Postprocedural pain was quantified on a visual analogue scale. Adverse events were evaluated by physical examination and the patients' self-report. RESULTS: The mean hair clearance at 3 months after three treatment sessions was 38.7% and 50.1% on the armpits treated with D1 and D3, respectively (p=0.028). Procedural pain was significantly greater in the side treated with D3 (p=0.009). Serious adverse events were not observed. CONCLUSION: Given that the pulse duration, fluence, and epidermal cooling were identical, the 805-nm LPDL at the three times larger spot size showed an efficacy improvement of 29.5% in axillary hair removal without serious adverse events.
Axilla ; Female ; Hair Removal* ; Hair* ; Humans ; Lasers, Semiconductor* ; Physical Examination

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
Administration, Oral ; Aging ; Animals ; Antibody Formation ; Cholesterol ; Diet ; Diet, High-Fat ; Homicide ; Hyperlipidemias* ; Inflammation ; Lymphocytes ; Mice ; Mice, Obese* ; Physiology ; Reference Values ; Rosuvastatin Calcium ; Rubus* ; Tumor Necrosis Factor-alpha

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.