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Objective Pre-treatment anxiety (PA) before chemotherapy increases complaints of chemotherapy-related symptoms (CRS). The results on the association have been inconsistent, and the effect of temperament remains unclear. We aimed to determine whether PA is a risk factor for CRS and the effect of differing temperaments on CRS.Methods This prospective study comprised 176 breast cancer patients awaiting adjuvant chemotherapy post-surgery. We assessed CRS, PA, and temperament using the MD Anderson Symptom Inventory (MDASI), the Hospital Anxiety and Depression Scale, and the short form of the Temperament and Character Inventory-Revised, respectively. The MDASI was re-administered three weeks after the first chemo-cycle.Results PA showed weak positive correlation with several CRS after the first cycle; no CRS was significantly associated with PA when pre-treatment depressive symptoms and baseline CRS were adjusted in multiple regression analysis. Moderation model analysis indicated that the PA effect on several CRS, including pain, insomnia, anorexia, dry mouth, and vomiting, was moderated by harm avoidance (HA) but not by other temperament dimensions. In particular, PA was positively associated with CRS in patients with low HA.Conclusion The results in patients with low HA indicate that more attention to PA in patients with confident and optimistic temperaments is necessary.

Hepatic fibrosis is the first stage of liver disease, and can progress to a chronic status, such as cirrhosis or hepatocellular carcinoma. Excessive production of extracellular matrix (ECM) components plays an important role in the development of fibrosis. Mechanistically, transforming growth factor beta (TGFβ)-induced phosphorylation of Smad is thought to be a key signaling pathway in the development of liver fibrosis. Although the natural isoquinoline alkaloid oxoglaucine (1,2,9,10-tetramethoxy-7H-dibenzo(de,g)quinolin-7-one) exerts numerous beneficial effects, including anti-cancer, anti-inflammatory, and anti-osteoarthritic effects in diverse cell types, the effects of oxoglaucine on liver fibrosis and fibrogenic gene expression have not been fully elucidated. The aim of this study is to evaluate the signaling pathway and antifibrotic activity of isoquinoline alkaloid oxoglaucine in TFGβ-induced hepatic fibrosis in vitro. Using Hepa1c1c7 cells and primary hepatocytes, we demonstrated that oxoglaucine treatment resulted in inhibition of the expression of fibrosis markers such as collagen, fibronectin, and alpha-SMA. Subsequent experiments showed that oxoglaucine suppressed TGFβ-induced phosphorylation of Smad2 and reactive oxygen species (ROS) generation, without altering cell proliferation. We further determined that the increase in Smad7 by oxoglaucine treatment is responsible for the inhibition of Smad2 phosphorylation and the anti-fibrogenic effects. These findings indicate that oxoglaucine plays a crucial role in suppression of fibrosis in hepatocytes, thereby making it a potential drug candidate for treatment of liver fibrosis.

Background: Vasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method. Methods: We prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (

Purpose Breast cancer has been reported to be common in middle-age, but little is known about the relationship between menopausal stage and the severity of chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients. Therefore, we examined the association between menopausal stage and CINV severity.Methods Participants were prospectively enrolled from a tertiary general hospital. We evaluated CINV severity of 187 breast cancer patients receiving adjuvant chemotherapy, using a Likert scale from 1 to 10, before chemotherapy (W0), 4 weeks after the first chemotherapy (W4), and 12 weeks (W12) after the first chemotherapy. Premenopause, perimenopause, and postmenopause period were classified by age 45 and 55 years, respectively. CINV severity at different time-points and change values in CINV severity (cCIN, cCIV) at each time point, relative to W0, were compared using a linear mixed modelResults Significant group-by-time interactions were observed for CIN (p = 0.011), CIV (p = 0.027), and cCIN (p = 0.030). In postmenopausal period women, unlike in premenopausal and perimenopausal period women, the mean change values for CIN and CIV at each time point relative to W0 were not significantly different. In the post-hoc analysis, there was a significant difference (p = 0.007) in cCIN at W4 between perimenopausal and postmenopausal period women.Conclusions Changes in CINV severity in breast cancer patients follow different patterns according to menopausal stage. Perimenopausal period women seem to be particularly susceptible to CINV. During chemotherapy, it is necessary to manage CINV with consideration of menopausal stage.

BackgroundThe relationship between elevated serum uric acid (SUA) levels and cardiovascular outcomes after stent implantation remains uncertain. This study sought to evaluate the impact of SUA on 12-month cardiovascular outcomes after stent implantation.MethodsWe performed a retrospective study of patients who successfully underwent stent implantation and enrolled 3,222 patients with coronary artery disease (CAD) from a single center. SUA levels were measured before stent implantation. The patients were divided into six groups (ResultsOver the 12-month follow-up period, there were 101 all-cause deaths and 218 MACCE. After adjustment for several parameters, the group with SUA levels of more than or equal to 8 mg/dL had significantly higher hazard ratios in the incidence of all-cause death or MACCE. The group with ConclusionsOur study identified a U-shaped association between SUA levels and cardiovascular outcomes during 12-month follow-up for males, but not for females. Further studies are warranted to clarify the sex differences between SUA levels and clinical outcomes.

Oxidative stress has been demonstrated to play a pivotal role in the pathological processes of many neurodegenerative diseases. In the present study, we demonstrated that Chrysanthemum boreale Makino extract (CBME) suppresses oxidative stress-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanism. Our observations revealed that CBME effectively protected neuronal cells against H2O2-induced cell death by preventing caspase-3 activation, Bax upregulation, Bcl-2 downregulation, activation of three mitogen-activated protein kinases (MAPKs), cAMP response element-binding protein (CREB) and NF-κB phosphorylation, and iNOS induction. These results provide evidence that CBME has remarkable neuroprotective properties in SH-SY5Y cells against oxidative damage, suggesting that the complementary or even alternative role of CBME in preventing and treating neurodegenerative diseases is worth further studies.

Photodynamic therapy (PDT) is a promising cancer treatment with fewer side effects, and it eliminates tumors in target tissues with reactive oxygen species produced by photosensitizers (PS) and light. In this study, we isolated methyl pheophorbide A, which induces photodynamic cell death in the U937 and SK-HEP-1 cells, from perilla leaves. Its potential as a material for the development of a new PS was also evaluated. The methyl pheophorbide A is a dark green porphyrin compound isolated from methanol extract of perilla leaves. Apoptosis occurred was methyl pheophorbide A treated and irradiated with light, and there was no significant change where light not treated. In both U937 and SK-HEP-1 cells, apoptotic body, vesicle formation, and DNA ladder were confirmed in the light-irradiated. The caspase-3/7 activity an important factor in apoptosis, was 101.50 ± 14.24% when treated with 0.25 μg/ml methyl pheophorbide A in U937, and 91.32 ± 16.23% when treated with 1.00 μg/ml in SK-HEP-1 cells. The apoptotic phenomenon appeared more strongly when the methyl pheophorbide A concentration was increased with irradiating light. This study demonstrates the isolation, identification, and phototoxic activity of methyl pheophorbide A in perilla leaves. We expect that this study will be useful in the search for PS candidates using natural products.

Syntenin acts as an adaptor and scaffold protein through its two PSD-95, Dlg, and ZO-1 (PDZ) domains, participating in multiple signaling pathways and modulating cellular physiology. It has been identified as an oncogene, promoting cancer development, metastasis, and angiogenesis in various carcinomas. Syntenin-1 is also associated with the production and release of exosomes, small extracellular vesicles that play a significant role in intercellular communication by containing bioactive molecules such as proteins, lipids, and nucleic acids. The trafficking of exosomes involves a complex interplay of various regulatory proteins, including syntenin-1, which interacts with its binding partners, syndecan and activated leukocyte cell adhesion molecule (ALIX). Exosomal transfer of microRNAs, a key cargo, can regulate the expression of various cancer-related genes, including syntenin-1. Targeting the mechanism involving the regulation of exosomes by syntenin-1 and microRNAs may provide a novel treatment strategy for cancer. This review highlights the current understanding of syntenin-1’s role in regulating exosome trafficking and its associated cellular signaling pathways.

We sought to investigate the effect of extracts from Rosa gallica petals (RPE) on skin whitening and anti-wrinkle activity. Tyrosinase activity was attenuated by RPE treatment, concomitant with the reduction of melanin accumulation in human B16F10 melanoma. Treatment of the facial skin of volunteers in a clinical trial with an RPE-containing formulation enhanced skin brightness (L* value) significantly. The underlying mechanism responsible was determined to be associated with mitogen-activated protein kinase (MAPK) activation. In addition, RPE exhibited anti-wrinkle formation activity of human dermal fibroblasts by suppressing matrix metalloproteinase (MMP)-1 level. In vivo study, RPE also inhibited solar ultraviolet-stimulated MMP-1 level by c-Jun regulation. Overall, our findings indicate that RPE evokes skin whitening and anti-wrinkle formation activity by regulating intracellular signaling, supporting its utility as an ingredient for skin whitening and anti-wrinkle cosmetic products.

Cracking and erosion are critical factors that reduce the mechanical properties and stability of concrete structures and soil, respectively. They are recognized worldwide as severe disasters causing the collapse of many structures including stone heritage and dams, and landslides. Therefore, it is essential to propose effective and environment-friendly management methods to prevent them. Carbonatogenesis has recently received considerable attention as a reliable biological process for remediating cracks in calcareous structures, stabilizing loose soils, and sequestering CO

Cytochrome P450 (CYP) catalyzes a wide variety of monooxygenation reactions in plant primary and secondary metabolisms. Land plants contain CYP703, belonging to the CYP71 clan, which catalyzes the biochemical pathway of fatty acid hydroxylation, especially in male reproductive tissues. Korean/Asian ginseng (Panax ginseng Meyer) has been regarded as one of important medicinal plant for a long time, however the molecular mechanism is less known on its development. In this study, we identified and characterized a CYP703A gene in P. ginseng (PgCYP703A4), regarding reproductive development. PgCYP703A4 shared a high-sequence identity (81–83%) with predicted amino acid as CYP703 in Dancus carota, Pistacia vera, and Camellia sinensis as well as 76% of amino acid sequence identity with reported CYP703 in Arabidopsis thaliana and 75% with Oryza sativa. Amino acid alignment and phylogenetic comparison of P. ginseng with higher plants and known A. thaliana members clearly distinguish the CYP703 members, each containing the AATDTS oxygen binding motif and PERH as a clade signature. The expression of PgCYP704B1 was only detected in P. ginseng flower buds, particularly in meiotic cells and the tapetum layer of developing anther, indicating the conserved role on male reproduction with At- and Os- CYP703. To acquire the clue of function, we transformed the PgCYP703A4 in A. thaliana. Independent overexpressing lines (PgCYP703A4ox) increased silique size and seed number, and altered the contents of fatty acids composition of cutin monomer in the siliques. Our results indicate that PgCYP703A4 is involved in fatty acid hydroxylation which affects cutin production and fruit size.

Sex (i.e., female sex) confers one point for the CHA2DS2-VASc score. For this reason, females with atrial fibrillation (AF) always have a CHA2DS2-VASc score of at least 1. To compare the CHA2DS2-VA (excluding female sex) and CHA2DS2-VASc scores in Korean AF patients using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke in nonvalvular AF patients between 2013 and 2017. The predictive values of the CHA2DS2-VA and CHA2DS2-VASc scores for ischemic stroke were evaluated using the C-statistic and net reclassification improvement (NRI). The primary outcome was the occurrence of ischemic stroke. A total of 185,637 patients with AF (49.7% women) were included in this study. The mean ages were 66.5 years for females and 64.9 years for males. The incidence of ischemic stroke in male patients was similar to females (3.63%/year vs. 3.72%/year, p = 0.273, respectively). In addition, no sex difference was apparent for stroke risk in AF patients stratified by risk factor component and age group. In the C-statistic analysis, the predictive ability of the CHA2DS2-VA score for ischemic stroke was similar to the CHA2DS2-VASc score. Additionally, CHA2DS2-VA performed better for predicting ischemic stroke in AF patients with risk scores of ≥2 (AUC 0.701 vs. 0.689, z = 4.596, p < 0.001) or those aged ≥75 years (AUC 0.715 vs. 0.701, z = 4.957, p < 0.001). In Korean AF patients, female sex is not a specific risk factor that contributes to the development of ischemic stroke. The CHA2DS2-VA score, which excludes female sex, may be a more suitable risk score for guiding anticoagulation decisions in Korean AF patients.

Cytochrome P450 (CYP) catalyzes a wide variety of monooxygenation reactions in plant primary and secondary metabolisms. Land plants contain CYP703, belonging to the CYP71 clan, which catalyzes the biochemical pathway of fatty acid hydroxylation, especially in male reproductive tissues. Korean/Asian ginseng (

Bottom ash (BA), a byproduct of coal combustion from electric power plants with a porous surface texture and high pH, may influence the physical and chemical properties of upland arable soil associated with nitrous oxide (N2O) emission from upland soil. This study evaluated the use of BA in mitigating N2O emissions from upland arable soil and increasing the crop yield. In a field experiment, N2O emitted from the soil was monitored weekly in a closed chamber over a 2-year period (2018–2019). BA was applied to upland soil at the rates of 0, 200, and 400 Mg·ha−1. Cumulative N2O emission significantly decreased with increasing BA application rate, it decreased by 55% with a BA application rate of 400 Mg·ha−1 compared with the control. Yield-scaled N2O emission decreased with increasing BA application rates of up to 200 Mg·ha−1. Water-filled pore spaces (WFPS) were 70.2%, 52.9%, and 45.3% at the rates of 0, 200, and 400 Mg·ha−1, respectively, during the growing season. For economic viability and environmental conservation, we suggest that BA application at a rate of 200 Mg·ha−1 reduces N2O emissions per unit of crop production.

The purpose of this longitudinal prospective cohort study was to investigate the role of chronotype in the incidence of chemotherapy-induced peripheral neuropathy (CIPN) among women with breast cancer. A total of 128 subjects with breast cancer awaiting adjuvant chemotherapy without peripheral neuropathy participated in this study. The presence of CIPN was defined as a response of 3 or higher on a peripheral neuropathy subscale in the MD Anderson Symptom Inventory. Candidate psychiatric factors associated with CIPN were assessed, using the Composite Scale of Morningness, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale. To examine the association between chronotype and CIPN, we built logistic regression models, adjusting for demographic, clinical, and other psychiatric variables. Forty-nine participants received a chemotherapy regimen containing docetaxel, of which 29 (59%) developed CIPN. We performed subgroup analyses of docetaxel-treated participants. The morning chronotype was inversely associated with CIPN (odds ratio, 0.07; confidence interval, 0.01–0.48; p = 0.016) after adjusting for age, BMI, education, alcohol use, smoking, disease stage, sleep quality, depression, and anxiety. Our results suggest that the morning chronotype is a protective factor against the development of CIPN in patients with breast cancer who were treated with docetaxel.

Inflammatory bowel diseases (IBD) induce inflammation in the colon and small intestine. IBD include ulcerative colitis and Crohn's disease, with such common symptoms as severe diarrhea, fever, and blood in the stool. In the current study, we explored the ability of peanut shell extract (PSE) to alleviate IBD in an experimental colonic inflammation model. Colitis was induced by orally administered dextran sulfate sodium (DSS) in mice. Peanut shell extract was prepared using a method of aqueous ethanol. DSS treatment reduced the colon length and mouse body weight, and aggravated disease condition compared with untreated control mice. Oral administration of 400 mg/kg PSE alleviated colon shortening, body weight loss, DAI, and colon injury score in DSS-induced colitis. These physiological improvements were validated by reduced levels of proinflammatory cytokines and infiltrating macrophage accumulation in the inflamed colon in the PSE administered group. These observations suggest that PSE may be developed as an alternative natural extract for the prevention or treatment of IBD.

The anti-skin inflammatory activities of rose petal extracts have been described in our previous study. Because skin inflammation is closely linked to skin aging, our study investigated the effects of Rosa gallica petals on skin aging-related activities such as skin whitening and anti-wrinkle properties. Each sample was prepared via extraction using different ethanol ratios with the objective of evaluationg optimal extraction conditions for industrial application. Aqueous 50% (v/v) EtOH extract of R. gallica petal significantly suppressed tyrosinase activity, melanin production, and solar UV-induced matrix metalloproteinase-1, a hall mark of wrinkle formation. In addition, the aqueous 50% (v/v) EtOH extract showed the highest antioxidative effect and had highest flavonoid contents, consistent with the reported anti-aging effects. Overall, our findings suggest that R. gallica petals extracts exhibit anti-aging effects. Furthermore, 50% EtOH extraction, in particular, was optimal for the highest anti-aging, and anti-oxidative effects as well as to obtain the highest flavonoid content.

The proper management of bleeding risk in patients undergoing percutaneous coronary intervention (PCI) is critical. Recently, the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria have been proposed as a standardized tool for predicting bleeding risk. We sought to compare the predictive performance of ARC-HBR criteria and the PRECISE-DAPT score for bleeding in Korean patients undergoing PCI. We recruited 1418 consecutive patients undergoing PCI from January 2012 through December 2018 (Dong-A University Medical Center, Busan, Korea). The ARC-HBR and PRECISE-DAPT scores showed a high AUC for three bleeding definitions (AUC 0.75 and 0.77 for BARC 3 to 5, AUC 0.68 and 0.71 for TIMI minor to major, AUC 0.81 and 0.82 for GUSTO moderate to severe, respectively) and all-cause death (AUC 0.82 and 0.82, respectively). When compared with the ARC-HBR score, the discriminant ability of the PRECISE-DAPT score was not significantly different for bleeding events and all-cause death. The ARC-HBR criteria and PRECISE-DAPT scores demonstrated reasonably good discriminatory capacity with respect to 1-year bleeding events in Korean patients treated with DAPT, regardless of the bleeding definition. Our findings also suggest that the simple PRECISE-DAPT score is as useful as ARC-HBR criteria in predicting bleeding and all-cause death after PCI.

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%, HR, 2.93, 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

Cereblon (CRBN), a primary target of immune-modulatory imide drugs (IMiDs), functions as a substrate receptor in the CUL4-RBX1-DDB1-CRBN (known as CRL4CRBN) E3 ubiquitin ligase complex. Binding of IMiDs to CRBN redirects the CRL4CRBN E3 ubiquitin ligase to recruit or displace its substrates. Interaction between CRBN and the AMPK α subunit leads to CRL4CRBN-dependent degradation of the γ subunit and inhibits AMPK activity. However, the effect of thalidomide on the function of CRBN as a negative regulator of AMPK through interaction with the α subunit remains unclear. Here, we show that thalidomide does not affect AMPK activation or the binding affinity between CRBN and the AMPK α subunit. Thalidomide had no effect on AMPK activity independent of CRBN expression. The N-terminal region and C-terminal tail of CRBN, which is distinct from the IMiD binding site, were critical for interaction with the AMPK α subunit. The present results suggest that CRL4CRBN negatively regulates AMPK through a pathway independent from the CRBN-IMiD binding region.

Biomineralization, a well-known natural phenomenon associated with various microbial species, is being studied to protect and strengthen building materials such as concrete. We characterized Rhodococcus erythreus S26, a novel urease-producing bacterium exhibiting CaCO3-forming activity, and investigated its ability in repairing concrete cracks for the development of environment-friendly sealants. Strain S26 grown in solid medium formed spherical and polygonal CaCO3 crystals. The S26 cells grown in a urea-containing liquid medium caused culture fluid alkalinization and increased CaCO3 levels, indicating that ureolysis was responsible for CaCO3 formation. Urease activity and CaCO3 formation increased with incubation time, reaching a maximum of 2054 U/min/mL and 3.83 g/L, respectively, at day four. The maximum CaCO3 formation was achieved when calcium lactate was used as the calcium source, followed by calcium gluconate. Although cell growth was observed after the induction period at pH 10.5, strain S26 could grow at a wide range of pH 4–10.5, showing its high alkali tolerance. FESEM showed rhombohedral crystals of 20–60 µm in size. EDX analysis indicated the presence of calcium, carbon, and oxygen in the crystals. XRD confirmed these crystals as CaCO3 containing calcite and vaterite. Furthermore, R. erythreus S26 successfully repaired the artificially induced large cracks of 0.4–0.6 mm width.

The asbestos victim relief schemes were introduced to resolve the issue of victims of asbestos-related diseases not receiving compensation through conventional legal orders. This article seeks to derive the differences and commonalities of various asbestos victim relief schemes available outside of the conventional occupational compensation system along with a systematic understanding and to propose plans for improvement through a comparative study. After the degree of asbestos exposure, the population, and the period of implementation were corrected, the recognized claims of the total of conventional occupational compensation schemes and the asbestos victim relief schemes could be ranked in the order of South Korea (KOR) (1867, total), France (FRA) (1571), Japan (JPN) (966), KOR (847, asbestosis grade 2,3 excluded), the United Kingdom (GBR) (670), and the Netherlands (NLD) (95). The average amount of compensation per person, in the case of mesothelioma, was higher in the order of FRA (4.60 times), KOR (1.46 times), GBR (1.03 times), and NLD (0.73 times) of the median income per year. The differences between countries were largely caused by the purpose of institutional design and influenced by the level of qualification, the existence of an expiration date, type of disease, type of benefit, level of judgment criteria, the existence of a procedure for appeals, and recognition rate (GBR: 102%, FRA: 84%, NLD: 81%, JPN: 76%, KOR: 73%, and BEL: 54%). Based on this analysis, suggestions could be made regarding the expansion of disease types, benefit types, and the overall review of judgment criteria. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:18 issue:10 ispartof: location:Switzerland status: published

Although safflower seed extract exhibits pharmacological activity against various diseases, the effects of its individual compounds on osteoarthritis (OA) have not been elucidated. Here, we evaluated the effects of these extracts and their single compounds on OA. N-(p-Coumaroyl) serotonin and N-feruloyl serotonin, main components of safflower seed extract, were isolated by high-performance liquid chromatography. Under in vitro OA mimic conditions, the expression of the matrix metalloproteinases (MMPs) MMP3/13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) ADAMTS5 were reduced in mouse chondrocytes treated with safflower seed extract. Furthermore, the oral administration of safflower seed extract attenuated cartilage destruction in a mouse OA model induced by destabilization of the medial meniscus. N-(p-Coumaroyl) serotonin and N-feruloyl serotonin, but not serotonin, reduced MMP3, MMP13, and ADAMTS5 expression in IL-1β-treated chondrocytes. Additionally, they significantly blocked the nuclear factor-κB (NF-κB) pathway by inhibiting IκB degradation and p65 phosphorylation. Our results suggest that safflower seed extract and its single compounds can attenuate cartilage destruction by suppressing MMP and ADMATS5 expression. The anti-arthritic effects are mediated by NF-κB signaling and involve the inhibition of IκB degradation and p65 phosphorylation. These results indicate that safflower seed extract may serve as a novel therapeutic agent against OA.

Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common chronic diseases that frequently co-exist. The link between OA and T2DM is attributed to common risk factors, including age and obesity. Several reports suggest that hyperglycemia and accumulated advanced glycosylation end-products might regulate cartilage homeostasis and contribute to the development and progression of OA. Metformin is used widely as the first-line treatment for T2DM. The drug acts by regulating glucose levels and improving insulin sensitivity. The anti-diabetic effects of metformin are mediated mainly via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), which is an energy sensing enzyme activated directly by an increase in the AMP/ATP ratio under conditions of metabolic stress. Dysregulation of AMPK is strongly associated with development of T2DM and metabolic syndrome. In this review, we discuss common risk factors, the association between OA and T2DM, and the role of AMPK. We also address the adaptive use of metformin, a known AMPK activator, as a new drug for treatment of patients with OA and T2DM.

Cudrania tricuspidata has diverse biological activities, such as antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. This study investigated the protective effects of C. tricuspidata fruit extracts (CTFE) against scopolamine (SCO)-induced neuron impairment. The neuroprotective effects of CTFE on SCO-induced memory dysfunction were confirmed in mice using the Barnes maze test. The results showed that co-treatment of SCO and CTFE increased the stay time in the target zone compared with SCO treatment alone. Similarly, the results obtained by the fear conditioning test revealed that SCO–CTFE co-treatment induced the freezing action time under both the contextual fear condition and the cued fear condition compared with SCO treatment alone. Moreover, we showed that CTFE reduced the SCO-induced acetylcholinesterase (AChE) activity, thereby increasing the acetylcholine concentration in mice hippocampal tissues. Consistent with the improvement of memory and recognition function in vivo, our in vitro results showed that CTFE induced cAMP response element binding protein (CREB) and extracellular regulated kinase 1/2 (ERK1/2) activity in PC12 cells and reduced SCO-induced AChE activity. In addition, the microarray results of the hippocampal tissue support our data showing that CTFE affects gene expressions associated with neurogenesis and neuronal cell differentiation markers such as spp1 and klk6. Overall, CTFE exerts a neuroprotective effect via regulation of the CREB and ERK1/2 signaling pathways and could be a therapeutic candidate for neurodegenerative diseases.

Cereblon (CRBN) is a substrate receptor of the cullin-RING E3 ubiquitin ligase (CRL) complex that mediates the ubiquitination of several substrates. In this study, CRBN knockout (KO) mice exhibited decreased levels of stratum corneum hydration (SCH) and collagen I expression with an elevated protein level of matrix metalloprotease 1 (MMP1). The absence of cereblon in the skin of CRBN KO mice mimics the damage caused by narrowband ultraviolet B (NB-UVB). The primary CRBN deficient mouse embryonic fibroblasts (MEFs) undergo G2/M-arrested premature senescence via protein signaling of p38 MAPK and its dependent p53/p21pathway. The absence of CRBN induced the markers of cellular senescence, such as the senescence-associated heterochromatin foci (SAHF), SA-β-Gal staining, and p21 upregulation while the ectopic expression of CRBN reversed the phenotypes of SA-β-Gal staining and p21 upregulation. Reversion of the decreased protein level of collagen I was demonstrated after the reintroduction of the CRBN gene back into CRBN KO MEFs, validating the promising role of CRBN as a potential regulator for the function of the skin barrier and its cellular homeostasis.

Cudrania tricuspidata has diverse biological activities, such as antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. This study investigated the protective effects of C. tricuspidata fruit extracts (CTFE) against scopolamine (SCO)-induced neuron impairment. The neuroprotective effects of CTFE on SCO-induced memory dysfunction were confirmed in mice using the Barnes maze test. The results showed that co-treatment of SCO and CTFE increased the stay time in the target zone compared with SCO treatment alone. Similarly, the results obtained by the fear conditioning test revealed that SCO-CTFE co-treatment induced the freezing action time under both the contextual fear condition and the cued fear condition compared with SCO treatment alone. Moreover, we showed that CTFE reduced the SCO-induced acetylcholinesterase (AChE) activity, thereby increasing the acetylcholine concentration in mice hippocampal tissues. Consistent with the improvement of memory and recognition function in vivo, our in vitro results showed that CTFE induced cAMP response element binding protein (CREB) and extracellular regulated kinase 1/2 (ERK1/2) activity in PC12 cells and reduced SCO-induced AChE activity. In addition, the microarray results of the hippocampal tissue support our data showing that CTFE affects gene expressions associated with neurogenesis and neuronal cell differentiation markers such as spp1 and klk6. Overall, CTFE exerts a neuroprotective effect via regulation of the CREB and ERK1/2 signaling pathways and could be a therapeutic candidate for neurodegenerative diseases.

Background This study examined phenomenological manifestations of delirium in advanced cancer patients by examining the factor structure of the Delirium Rating Scale-Revised-98 (DRS-R-98) and profiles of delirium symptoms. Methods Ninety-three patients with advanced cancer admitted to inpatient palliative care units in South Korea were examined by psychiatrists using the DRS-R-98 and the Confusion Assessment Method (CAM). The factor structure of the DRS-R-98 was examined by exploratory structural equation modelling analysis (ESEM) and profiles of delirium were examined by latent profile analysis (LPA). Results CAM-defined delirium was present in 66.6% (n = 62) of patients. Results from the ESEM analysis confirmed applicability of the core and noncore symptom factors of the DRS-R-98 to advanced cancer patients. LPA identified three distinct profiles of delirium characterizing the overall severity of delirium and its core and noncore symptoms. Class 1 (n = 55, 59.1%) showed low levels of all delirium symptoms. Class 2 (n = 17, 18.3%) showed high levels of core symptoms only, whereas Class 3 (n = 21, 22.6%) showed high levels of both core and noncore symptoms except motor retardation. Conclusions Clinical care for delirium in advanced cancer patients may benefit from consideration of the core and noncore symptom factor structure and the three distinct phenomenological profiles of delirium observed in the present study.

Background The CHA 2 DS 2 ‐VASc score has been validated for stroke risk prediction in patients with atrial fibrillation (AF). Antithrombotic therapy is not recommended for low‐risk patients with AF (CHA 2 DS 2 ‐VASc 0 [male] or 1 [female]). We studied a cohort of initially low‐risk patients with AF in relation to their development of incident comorbidities and their treatment on oral anticoagulation therapy. Methods and Results We assessed data from 14 441 low‐risk patients with AF (CHA 2 DS 2 ‐VASc score of 0 [male] or 1 [female]) using the Korean National Health Insurance Service database, in relation to their development of incident stroke risk factors and adverse outcomes. The clinical end point was the occurrence of ischemic stroke, major bleeding, all‐cause death, or the composite outcome (ischemic stroke + major bleeding + all‐cause death). In our cohort, 2615 (29.1%) male and 1650 (30.3%) female patients acquired at least 1 new stroke risk factor during a mean follow‐up of 2.0 years. Among the patients with an increasing CHA 2 DS 2 ‐VASc score ≥1, male and female patients treated with oral anticoagulants had a significantly lower risk of ischemic stroke (male: hazard ratio [HR], 0.62 [95% CI, 0.44–0.82; P =0.003]; female: HR, 0.65 [95% CI, 0.47–0.84; P =0.007]), all‐cause death (male: HR, 0.67 [95% CI, 0.49–0.88; P =0.009]; female: HR, 0.82 [95% CI, 0.63–1.02; P =0.185]), and composite outcomes (male: HR, 0.78 [95% CI, 0.61–0.95; P =0.042]; female: HR, 0.79 [95% CI, 0.62–0.96; P =0.045]) than patients not treated with oral anticoagulants. Conclusions Approximately 30% of patients acquired ≥1 stroke risk factor over a 2‐year follow‐up period. Low‐risk patients with AF should be regularly reassessed to adequately identify those with incident stroke risk factors that would merit thromboprophylaxis for the prevention of stroke and the composite outcome.

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Delirium is a common neurocognitive complication in cancer. Despite this, the studies examining the trajectory of the severity of delirium symptoms and its impact on health outcome in gastric cancer is rather limited. This study examined the trajectory of delirium symptom severity (DSS) following resection surgery for gastric cancer and its prospective association with cognitive function. A three-wave prospective observational study was conducted with 242 gastric cancer patients admitted for resection surgery at a teaching hospital in South Korea from May 2016 to November 2017. DSS was assessed by the clinical staff before and 1, 2, 3, and 7 days after surgery using the Delirium Rating Scale-Revised-98. A survey including the Functional Assessment of Cancer Therapy-Cognitive Scale (FACT-Cog) and Mini-Mental State Examination (MMSE) was administered before surgery (T0), 7 days after (T1), and 3 to 6 months after surgery (T2). Out of 242 participants, 48.8% (118) completed the survey at all three time points, 43.4% (105) did so for two time points, and 7.9% (19) for one time point. No cases of full delirium were observed over four postoperative time points. Latent growth curve modeling analyses indicated that DSS declined over 3 days after surgery. Age and anesthesia time were positively associated with the initial level of DSS. A medication history for memory complaints was related to a slower recovery from delirium symptoms. While the use of propofol as an anesthetic agent was associated with lower initial DSS, it predicted a slower recovery from DSS. A higher initial DSS predicted a lower T1 MMSE score. Severity of postoperative delirium symptoms predicts a short-term and objective cognitive function post-surgery. Monitoring and timely treatment of postoperative delirium symptoms is needed to diminish cognitive consequences in gastric cancer patients.

This study suggests sulfuretin as an ant-skin aging agent. Sulfuretin significantly reduces solar UV (sUV)-increased matrix metalloproteinase-1 (MMP-1) expression and c-Jun phosphorylation in human dermal fibroblasts as well as skin tissue. An examination of the underlying mechanisms showed that sUV-activated MAPK signaling pathways are blocked by sulfuretin. Interestingly, sulfuretin directly inhibits the kinase activity of selected Src family. Because the amino acid sequence of Hck kinase which used kinase array is 230–497, it was assumed that sulfuretin interacts with this conserved domain of Src family kinase. It was also found that sulfuretin directly binds to sulfuretin with the lowest binding energy of −8.9 kcal/mol and free energy of −10.07 kcal/mol. Additionally, Hck protein was precipitated with sulfuretin-conjugated Sepharose 4B beads in HDFs cell lysate. Overall, present findings indicated that sulfuretin plays the role of anti-skin aging agent by acting as a general Src family kinase inhibitor in human skin.

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.