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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 and objective Lipid metabolism dysregulation has been implicated in the pathogenesis of IPF; however, the roles of most lipid metabolites in lung fibrosis remain unexplored. Therefore, we aimed to identify changes in lipid metabolites in the lung tissues of IPF patients and determine their roles in pulmonary fibrosis. Methods Free fatty acids in the lung tissues of IPF patients and controls were quantified using a metabolomic approach. The roles of free fatty acids in fibroblasts or epithelial cells treated with TGF-β1 were evaluated using fibrotic markers. The antifibrotic role of stearic acid was also assessed in a bleomycin-induced lung fibrosis mouse model. Protein levels in cell lysates or tissues were measured by western blotting. Results The levels of stearic acid were lower in IPF lung tissues than in control lung tissues. Stearic acid significantly reduced TGF-β1-induced α-SMA and collagen type 1 expression in MRC-5 cells. Furthermore, stearic acid decreased the levels of p-Smad2/3 and ROS in MRC-5 cells treated with TGF-β1 and disrupted TGF-β1-induced EMT in Beas-2B cells. Stearic acid reduced the levels of bleomycin-induced hydroxyproline in a mouse model. Conclusion Changes in the free fatty acid profile, including low levels of stearic acid, were observed in IPF patients. Stearic acid may exert antifibrotic activity by regulating profibrotic signalling.

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.

Background and purpose 3'-Sialyllactose (3'-SL) is a safe compound that is present in high levels in human milk. Although it has anti-inflammatory properties and supports immune homeostasis, its effect on collagen-induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3'-SL on the progression of rheumatoid arthritis (RA) in in vitro and in vivo models. Experimental approach The anti-arthritic effect of 3'-SL was analysed with fibroblast-like synoviocytes in vitro and an in vivo mouse model of CIA. RT-PCR, Western blotting and ELISA were performed to evaluate its effects in vitro. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin-O and haematoxylin staining. Key results 3'-SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3'-SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro-inflammatory cytokines, matrix metalloproteinases and osteoclastogenesis via NF-κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF-κB signalling pathway, was totally blocked by 3'-SL in the RA models. Conclusions and implications 3'-SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated via blockade of the NF-κB signalling pathway. Therefore, 3'-SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.

Background Precise assessment of health-related quality of life (HRQOL) with a reliable and valid measure is a prerequisite to the enhancement of HRQOL. This study examined the psychometric properties of the Korean version of the Medical Outcomes Study HIV Health Survey (K-MOS-HIV). Methods The reliability and validity of the K-MOS-HIV were examined in a multicenter survey involving 201 outpatients with human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) from four teaching hospitals throughout Korea. Results Ceiling effects were observed in six subscales scores, particularly, for the role functioning (71.1%), social functioning (63.2%), and pain (48.8%) scores. The Cronbach’s α for the physical health summary and mental health summary were 0.90 and 0.94, respectively, and it ranged from 0.78 to 0.95 for the subscales. The results of the exploratory structural equation modeling supported the two-factor structure of the K-MOS-HIV (physical health summary and mental health summary). An examination of the mean square statistics values from the Rasch analysis showed that the information-weighted fit and outlier-sensitive fit statistics were within the acceptable ranges of 0.6–1.4 except for two items in the mental health summary. The convergent validity of the K-MOS-HIV was supported by its significant positive correlations with the World Health Organization Quality of Life-HIV-BREF subscale scores. Its known-group validity was proven with its ability to detect significant differences in several K-MOS-HIV subscale scores among participants with different sociodemographic and clinical characteristics. Conclusions The K-MOS-HIV health survey appears to be a reliable and valid measure of HRQOL.

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p

Mutations in thecereblon(CRBN) gene cause human intellectual disability, one of the most common cognitive disorders. However, the molecular mechanisms ofCRBN-related intellectual disability remain poorly understood. We investigated the role ofCRBNin synaptic function and animal behavior using male mouse andDrosophilamodels.Crbnknock-out (KO) mice showed normal brain and spine morphology as well as intact synaptic plasticity; however, they also exhibited decreases in synaptic transmission and presynaptic release probability exclusively in excitatory synapses. Presynaptic function was impaired not only by loss of CRBN expression, but also by expression of pathogenic CRBN mutants (human R419X mutant andDrosophilaG552X mutant). We found that the BK channel blockers paxilline and iberiotoxin reversed this decrease in presynaptic release probability inCrbnKO mice. In addition, paxilline treatment also restored normal cognitive behavior inCrbnKO mice. These results strongly suggest that increased BK channel activity is the pathological mechanism of intellectual disability inCRBNmutations.SIGNIFICANCE STATEMENTCereblon(CRBN), a well known target of the immunomodulatory drug thalidomide, was originally identified as a gene that causes human intellectual disability when mutated. However, the molecular mechanisms of CRBN-related intellectual disability remain poorly understood. Based on the idea that synaptic abnormalities are the most common factor in cognitive dysfunction, we monitored the synaptic structure and function ofCrbnknock-out (KO) animals to identify the molecular mechanisms of intellectual disability. Here, we found thatCrbnKO animals showed cognitive deficits caused by enhanced BK channel activity and reduced presynaptic glutamate release. Our findings suggest a physiological pathomechanism of the intellectual disability-related geneCRBNand will contribute to the development of therapeutic strategies forCRBN-related intellectual disability.

Biocalcification is a natural biochemical process, which has been regarded as a promising method for sequestering heavy metals or carbon dioxide in the environment, healing cracks in concrete structures, and stabilizing soil. One of the key factors in this process is calcium carbonate-producing bacteria. The purpose of this study was to maximize the production of calcium carbonate by alkaliphilic Bacillus psychrodurans LC40 isolated from a limestone cave, by manipulating the medium composition for fast and non-detrimental crack healing, and to investigate the mechanism of its production. Strain LC40 could grow well in the strongly alkaline region (pH 9.5–11), indicating its alkaliphilic nature. The optimal medium for calcium carbonate production contained 2% tryptone, 1.5% urea, 0.15% NaHCO3, and 150 mM calcium formate (pH 6). Using this medium, the yield of calcium carbonate at 72 h was approximately 8.6-fold higher than that obtained through Urea-CaCl2 medium. In this culture, the urease and carbonic anhydrase activities were observed simultaneously, and the pH of the medium was found to have increased to 9.4, leading to maximum calcium carbonate production. This suggests that this pH value is achieved by the synergistic action of the two enzymes, resulting in a high calcium carbonate yield. The crystals were characterized by FESEM, EDS and XRD, which confirmed the production of rhombohedral and spherical calcium carbonate crystals containing vaterite and calcite. Strain LC40 completely healed a 0.75 mm wide crack in a very short time of 3 days using the optimized medium as a cementation solution. Our findings indicate that B. psychrodurans LC40 could be a promising candidate for the development of eco-friendly biosealant applicable to environmentally stressed concrete structures.

Oxysterols are oxygenated cholesterol derivatives and important regulators of cholesterol metabolism, lipid homeostasis, the immune system, and membrane fluidity regulation. Although the detailed mechanism of action of oxysterols remains unclear, activation of some nuclear receptors, such as liver X receptor α (LXRα) and RAR-related orphan receptors, have been believed to be critical for the regulation of various physiological processes in multiple tissues. 27-Hydroxycholesterol (27-OHC) is an endogenous oxysterol, which has an intermediate function in cholesterol catabolism to bile acid synthesis. According to previous studies, however, there are opposing opinions on whether 27-OHC activates human LXR. Recently, several studies have shown that 27-OHC can activate or inhibit the function of estrogen receptors ERα and ERβ in a tissue-specific manner, indicating that the understanding of 27-OHC-mediated biological output is very complicated. This review summarizes the pathophysiological relevance of 27-OHC in various tissues, with a special discussion on their functions in human diseases.

Cynanchum wilfordii Hemsley is a traditional herbal medicine that has been widely used in Asia. In the present study, we investigated the MMP-1 suppressing activity of a high-molecular weight fraction isolated from the roots of C. wilfordii Hemsley (HMF). In human skin tissue, UVB irradiation significantly increased matrix metalloproteinase-1 (MMP-1) expression, while HMF suppressed this effect. The inhibitory effect of HMF was confirmed in both primary human dermal fibroblasts (HDFs) and a human keratinocyte (HaCaT) model. An investigation of the underlying mechanisms responsible revealed that MKK4-JNK, MEK-ERK, and MKK3/6-p38 phosphorylation was downregulated by HMF treatment. HMF also induced a 30–40% increase in DPPH radical scavenging activity and recovered expression levels of the antioxidant enzyme superoxide dismutase. Taken together, these findings suggest that HMF elicits MMP-1 suppressing activity via inhibition of the signaling that drives UVB-induced oxidative stress in human skin.

To investigate efficacy of over-glasses patching treatment for amblyopic children using visual function improvement and Amblyopia Treatment Index (ATI) changes. In a randomized multi-center controlled clinical trial, 107 children aged 3–7 years with moderate amblyopia (visual acuity in the range of 20/40 to 20/100) were included to receive treatment with either an adhesive skin patch or a fabric over-glasses patch. The patients were prescribed 2 h of patching per day for the sound eye. Best-corrected visual acuity (BCVA) was investigated and ATI questionnaires were collected from parents at 5 weeks and 17 weeks after the initiation of treatment. ATI identifies barriers and problems associated with amblyopia treatment. We compared the changes of visual acuity of amblyopic eyes and ATI scores in two groups. At 17 weeks, the mean visual acuity of the amblyopic eye using Snellen chart improved 3.2 lines in the adhesive patching group and 2.7 lines for an over-glasses patching method that fit over eyeglasses (p = 0.345). A similar proportion of subjects in each group had improvement of ≥ 2 lines (adhesive patching group 67% vs over-glasses patching group 67%, p = 0.372). There was also no difference in treatment burden in each group as measured with the Amblyopia Treatment Index. The only item to demonstrate a significant difference between groups was that related to “Treatment makes the eye or eyelids red” (mean 4.0 ± 1.1 vs 3.0 ± 1.0 at 17 weeks, p = 0.001, for adhesive vs over-glasses patch). Over-glasses patching treatment is a useful option for amblyopia treatment when the patients suffer from adverse effects of using adhesive skin patching.

3′‐Sialyllactose has specific physiological functions in a variety of tissues; however, its effects on osteoarthritic development remain unknown. Here, we demonstrated the function of 3′‐sialyllactose on osteoarthritic cartilage destruction. In vitro and ex vivo, biochemical and histological analysis demonstrated that 3′‐sialyllactose was sufficient to restore the synthesis of Col2a1 and accumulation of sulphated proteoglycan, a critical factor for cartilage regeneration in osteoarthritic development, and blocked the expression of Mmp3, Mmp13 and Cox2 induced by IL‐1β, IL‐6, IL‐17 and TNF‐α, which mediates cartilage degradation. Further, reporter gene assays revealed that the activity of Sox9 as a transcription factor for Col2a1 expression was accelerated by 3′‐sialyllactose, whereas the direct binding of NF‐κB to the Mmp3, Mmp13 and Cox2 promoters was reduced by 3′‐sialyllactose in IL‐1β‐treated chondrocytes. Additionally, IL‐1β induction of Erk phosphorylation and IκB degradation, representing a critical signal pathway for osteoarthritic development, was totally blocked by 3′‐sialyllactose in a dose‐dependent manner. In vivo, 3′‐sialyllactose protected against osteoarthritic cartilage destruction in an osteoarthritis mouse model induced by destabilization of the medial meniscus, as demonstrated by histopathological analysis. Our results strongly suggest that 3′‐sialyllactose may ameliorate osteoarthritic cartilage destruction by cartilage regeneration via promoting Col2a1 production and may inhibit cartilage degradation and inflammation by suppressing Mmp3, Mmp13 and Cox2 expression. The effects of 3′‐sialyllactose could be attributed in part to its regulation of Sox9 or NF‐κB and inhibition of Erk phosphorylation and IκB degradation. Taken together, these effects indicate that 3′‐sialyllactose merits consideration as a natural therapeutic agent for protecting against osteoarthritis.

Little research has examined the role of pain catastrophizing (PC) in predicting suicide among patients with rheumatic disease or the mechanisms through which it works. This study examines whether depression, perceived social support (PSS), and perceived burdensomeness (PB) mediate the relationship between PC and suicide risk. It also examines the relative importance of sociodemographic, clinical, and psychological factors in predicting suicide risk. Three hundred sixty patients from a rheumatology clinic in Korea completed measures of pain catastrophizing, social support, depression, and perceived burdensomeness. In hierarchical multiple regression analysis, the PC magnification, PB, physical disability, and PSS were significantly related to suicide risk. Results of the serial multiple mediation analysis indicated that the total indirect effect of PC magnification on suicide risk was significant while the direct effect was not. Four specific indirect effects of PC magnification were found to be statistically significant. First of all, PC magnification was associated with suicide risk through PB and through depression and PB. PC magnification was also associated with suicide risk through depression and PSS. Lastly, PC magnification was associated with suicide risk through depression, PSS, and PB. The identified pathways through which PC affects suicide risk suggest the importance of depression, PSS, and PB. Evaluation and intervention targeted at physical disability and the psychological factors of PC magnification, depression, PSS, and PB may be integrated into the management of suicide risk in patients with rheumatic disease.

To examine factors in the fear-avoidance model, such as pain, pain catastrophizing, fear-avoidance beliefs, physical disability, and depression and their relationships with physical and psychological quality of life in patients with rheumatic diseases.The data were obtained from 360 patients with rheumatic diseases who completed self-report measures assessing study variables. Structural equation modeling was used to examine the hypothesized relationships among factors specified in the fear-avoidance model predicting physical and psychological quality of life.Final models fit the data well, explaining 96% and 82% of the variance in physical and psychological quality of life, respectively. Higher pain catastrophizing was related to stronger fear-avoidance beliefs that had a direct negative association with physical disability and depression, which, in turn, negatively affected physical quality of life. Pain severity was also directly related to physical disability. Physical disability also affected physical quality of life indirectly through depression. The hypothesized relationships specified in the model were also confirmed for psychological quality of life. However, physical disability had an indirect association with psychological quality of life via depression.The current results underscore the significant role of cognitive, affective, and behavioral factors in perceived physical disability and their mediated detrimental effect on physical and psychological quality of life in patients with rheumatic diseases. Implications for rehabilitation The fear-avoidance model is applicable to the prediction of quality of life in patients with rheumatic diseases. As pain-catastrophizing and fear-avoidance beliefs are important factors linked to physical disability and depression, intervening these cognitive factors is necessary to improve physical function and depression in patients with rheumatic diseases. Considering the strong association between depression and physical and psychological quality of life, the assessment and treatment of the former should be included in the rehabilitation of patients with rheumatic diseases. Interventions targeting physical function and depression are likely to be effective in terms of improving physical and psychological quality of life in patients with rheumatic diseases.

We compared the long-term outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease in a real-world population.CABG is the standard of care for ULMCA disease. Contemporary randomized trials have reported conflicting results with the two revascularization strategies for the treatment of ULMCA disease at intermediate-term follow-up.We evaluated 422 consecutive patients with ULMCA disease who underwent CABG (n = 273) or PCI (n = 149) from 1998-2008. The primary outcome measure was major adverse cardiac and cerebrovascular event (MACCE) rate, defined as the composite of all-cause death, myocardial infarction (MI), stroke, or target-vessel revascularization (TVR) at 10 years. Propensity-score matched (PSM) analysis was used to assess long-term MACCE.The cumulative 10-year incidence of risk for MACCE was not significantly different between the PCI and CABG groups (24.8% vs 20.5%, respectively; log rank P=.22; log rank PSM P=.45). The risk for all-cause death was not significantly different between the two groups (log rank P=.09; PSM log rank P=.51). The risk for stroke was significantly lower with PCI (log rank P=.02), but was not significant after matching (PSM log rank P=.27). The risk for TVR was significantly higher with PCI vs CABG prior to and after matching (log rank P.001; log rank PSM P=.01). There were no significant differences in MACCE between the two groups when stratified by SYNTAX scores ≤22% (log rank P=.61) and23% (log rank P=.06).In patients with ULMCA disease, PCI was comparable with CABG for long-term MACCE and death rates. The TVR rate was higher in the PCI group.

Background: The optimal strategy to manage chronic total occlusion (CTO) remains unclear. The Japanese CTO multicenter registry (J-CTO) score is an established tool for predicting successful recanalization. However, it does not take into account nonangiographic predictors for final technique success. In the present study, we designed and tested a scoring model called the Busan single-center CTO registry (B-CTO) score combining clinical and angiographic characteristics to predict successful CTO recanalization in Korean patients. Methods: Prospectively enrolled CTO patients (n = 438) undergoing coronary intervention (1999-2015) were assessed. The B-CTO score comprises 6 independent predictors: age 60-74 years and lesion length ≥20 mm were assigned 1 point each, while age ≥75 years, female gender, lesion location in the right coronary artery, blunt stump, and bending >45° were assigned 2 points each. For each predictor, the points assigned were based on the associated odds ratio by multivariate analysis. The lesions were classified into 4 groups according to the summation of points scored to assess the probability of successful CTO recanalization: easy (score 0-1), intermediate (score 2-3), difficult (score 4-5), and very difficult (score ≥6). CTO opening was designated as the primary endpoint regardless of the interventional era or the skill of the operator. Results: The final success rate for B-CTO was 81.1%. The probability of successful recanalization for patient groups classified as easy (n = 64), intermediate (n = 148), difficult (n = 134), and very difficult (n = 92) was 95.3, 86.5, 79.1 and 65.2%, respectively (p for trend Conclusions: The B-CTO score has been designed and validated in Korean patients with native coronary CTO and is an improved tool for predicting successful recanalization. Wider application of the B-CTO score remains to be explored.

Background Medical students face a variety of stressors associated with their education; if not promptly identified and adequately dealt with, it may bring about several negative consequences in terms of mental health and academic performance. This study examined psychometric properties of the Korean version of the Higher Education Stress Inventory (K-HESI). Methods The reliability and validity of the K-HESI were examined in a large scale multi-site survey involving 7110 medical students. The K-HESI, Beck Depression Inventory (BDI) and questions regarding quality of life (QOL) and self-rated physical health (SPH) were administered. Results Exploratory factor analysis of the K-HESI identified seven factors: Low commitment; financial concerns; teacher-student relationship; worries about future profession; non-supportive climate; workload; and dissatisfaction with education. A subsequent confirmatory factor analysis supported the 7-factor model. Internal consistency of the K-HESI was satisfactory (Cronbach’s α = .78). Convergent validity was demonstrated by its positive association with the BDI. Known group validity was supported by the K-HESI’s ability to detect significant differences on the overall and subscale scores of K-HESI according to different levels of QOL and SPH. Conclusions The K-HESI is a psychometrically valid tool that comprehensively assesses various relevant stressors related to medical education. Evidence-based stress management in medical education empirically guided by the regular assessment of stress using reliable and valid measure is warranted.

The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4(+) T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4(+) T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell-specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4(+) T-cell activation via epigenetic regulation of Kv1.3 expression.

Cholesterol homeostasis is mediated by Scap, a polytopic endoplasmic reticulum (ER) protein that transports sterol regulatory element-binding proteins from the ER to Golgi, where they are processed to forms that activate cholesterol synthesis. Scap has eight transmembrane helices and two large luminal loops, designated Loop1 and Loop7. We earlier provided indirect evidence that Loop1 binds to Loop7, allowing Scap to bind COPII proteins for transport in coated vesicles. When ER cholesterol rises, it binds to Loop1. We hypothesized that this causes dissociation from Loop7, abrogating COPII binding. Here we demonstrate direct binding of the two loops when expressed as isolated fragments or as a fusion protein. Expressed alone, Loop1 remained intracellular and membrane-bound. When Loop7 was co-expressed, it bound to Loop1, and the soluble complex was secreted. A Loop1-Loop7 fusion protein was also secreted, and the two loops remained bound when the linker between them was cleaved by a protease. Point mutations that disrupt the Loop1-Loop7 interaction prevented secretion of the Loop1-Loop7 fusion protein. These data provide direct documentation of intramolecular Loop1-Loop7 binding, a central event in cholesterol homeostasis.

With the enhancement of built-in communication capabilities in various meters and wearable devices, which implies Internet of things (IoT), the demand of small-area embedded processors has increased. In this paper, we introduce a small-area 32-bit pipelined processor, Juno, which is available in the field of IoT. Juno is an EISC (Extendable Instruction Set Computer) machine and has a 2/3-stage pipeline structure to reduce the data dependency of the pipeline. It has a simple pipeline controller which only controls the program counter (PC) and two pipeline registers. It offers $32{\times}32

This study examined whether somatic symptoms and sleep quality can be indicators of depression and suicide risk in Korean military conscripts. In October and November of 2016, a total of 1,937 conscripts completed a survey that included the patient health questionnaire (PHQ) 9, PHQ15, the Mini International Neuropsychiatric Interview Plus suicidality module, and the Pittsburgh sleep quality index. Four groups were formed by depression and suicide risk status. Results from analyses of covariance indicated that overall, the severity of somatic symptoms and aspects of sleep quality were higher in conscripts with both depression and suicide risk, and greater associations of depression with somatic symptoms and sleep quality. The results of logistic regression analyses indicated that moderate to high levels of somatic symptoms and poorly perceived health were associated with the risk of depression and suicide, respectively. Poor sleep quality was associated with a higher risk of depression, but it was not significantly related to suicide risk after accounting for depression, which showed a greater association with suicide risk. Monitoring somatic and sleep complaints along with perceived health are needed as potential markers of depression and suicide risk among military conscripts.

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.

Our objective was to compare the predictive performance between the HAS-BLED, ATRIA, and PRECISE-DAPT score in AF patients using antiplatelet agents or anticoagulants We recruited 1,114 consecutive AF patients (51% male; median age, 71 years) receiving antiplatelet agents or oral anticoagulants

Few studies have examined the effect of perceived social support (PSS) on chemotherapy-related symptoms (CRS). This study examined the effect of PSS on CRS in 184 patients with breast cancer.Participants were consecutively enrolled from a tertiary general hospital in Seoul, South Korea. CRS were assessed eight times, from before the first neoadjuvant chemotherapy to six months after the end of neoadjuvant chemotherapy, with the MD Anderson Symptom Inventory. PSS was evaluated once, before the first neoadjuvant chemotherapy session, using the Multidimensional Scale of Perceived Social Support (MSPSS). Two groups were formed based on MSPSS scores: the low PSS group (n = 62) and the moderate-to-high PSS group (n = 122). Linear mixed model analyses were used to compare the change in CRS severity between the two groups during chemotherapy.Results indicated a significant group-by-time (low PSS or moderate-to-high PSS; 8 periods of chemotherapy) interaction for pain (p = .005), nausea (p = .033), insomnia (p .001), distress (p = .003), dyspnea (p = .014), memory loss (p = .021), vomiting (p = .016), and numbness (p = .008) in which the moderate-to-high PSS group showed significantly lower levels of increase in those symptoms during chemotherapy. Moreover, the effect of PSS on CRS differed depending on the sources of PSS.Patients with moderate-to-high PSS experience less severe CRS compared with patients with low PSS during chemotherapy. The current findings indicate the potential benefits of providing social support in the management of CRS.

D2B time is important in STEMI patients. However, it is not well known whether there are further differences present within D2B time < 90 minutes. From the Korean Registry of Regional Cardiocerebrovascular Center for Acute Myocardial Infarction (Jul, 2016 - Sep, 2018), patients over 18 years old

Background: Dual antiplatelet therapy (DAPT) helps prevent ischemic events after coronary stenting but comes with an increased risk of bleeding. Several risk scores have been proposed for the management of patients receiving DAPT, but no standardized tool exists for the purpose. We sought to compare the performance of the new PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy), CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines), and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) scores for the prediction of bleeding in Korean patients receiving DAPT. Methods and Results: Nine hundred and four consecutive patients who underwent stent implantation received DAPT. One-year bleedings were assessed using TIMI (Thrombolysis in Myocardial Infarction), GUSTO (Global Use of Strategies to Open Occluded Arteries), and BARC (Bleeding Academic Research Consortium). Bleeding events occurred in 154 patients (17.0%) by BARC type ≥3a criteria, 119 patients (13.2%) by the TIMI minor or major criteria, and 80 patients (8.8%) by the GUSTO moderate or severe criteria. In the C statistic analysis, CRUSADE, ACUITY, and PRECISE-DAPT scores showed high area under the curve values for 1-year bleeding (area under the curve 0.73, 0.75, and 0.75 for TIMI minor or major bleeding; area under the curve 0.81, 0.79, and 0.82 for GUSTO moderate to severe; and area under the curve 0.79, 0.81, and 0.81 for BARC type ≥3a, respectively). The discriminate ability of PRECISE-DAPT was similar to CRUSADE and ACUITY in bleeding complications. However, the PRECISE-DAPT score was better at reclassifying the risk of 1-year bleeding compared with ACUITY for the 3 bleeding criteria. Conclusions: The PRECISE-DAPT score is a simple 5-item risk score that represents a standardized tool for the prediction of 1-year bleeding in Korean patients receiving DAPT, regardless of bleeding definition.

The high disease burden associated with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is linked to the elevated suicide risk in this population. Informed by the interpersonal theory of suicide, this study examined how and under which conditions depression is related to suicide risk in people living with HIV/AIDS. A total of 202 outpatients with HIV/AIDS participated in a cross-sectional and multi-center survey involving four university hospitals in South Korea. This self-reported survey included the Hospital Anxiety and Depression Scale, Interpersonal Needs Questionnaire, and Mini-International Neuropsychiatric Interview suicidality module. Participants’ mean age was 48.6 (SD = 13.4) and the majority was male (89.1%). The proportions of those at high, medium, and low suicide risk were 18.5%, 20%, and 15.4%, respectively. Depression was associated with suicide risk directly and indirectly by increasing perceived burdensomeness (PB) and the indirect effect of depression on suicide risk mediated by PB was contingent on the level of thwarted belongingness (TB). PB was associated with suicide risk even after controlling for depression, suggesting its independent effect on suicide risk. PB and TB are potential mechanisms through which depression is associated with suicide risk, supporting the applicability of the interpersonal theory of suicide to understanding a complex interplay of risk factors in people with HIV/AIDS. Moreover, given the independent association of PB with suicide risk, as well as a protective effect of TB in suicide risk, monitoring and management of these factors should be included in the care of people with HIV/AIDS.

Background Subsyndromal delirium, a condition in which patients exhibit some, but not all, of the symptoms of delirium, can negatively affect the outcomes of patients with cancer. However, the incidence of subsyndromal delirium in patients with gastric cancer is unknown. Here, we investigated the incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer. Methods We recruited consecutive patients with gastric cancer who were scheduled for curative resection at a tertiary hospital. Patients’ subsyndromal delirium symptoms were serially assessed preoperatively and 1, 2, 3, and 7 days postoperatively using the Delirium Rating Scale-Revised-98 (DRS-R-98). A DRS-R-98 score of 8–14 at any postoperative assessment was considered to indicate subsyndromal delirium. Sociodemographic and pre−/intra-operative clinical data were also assessed. Logistic regression analyses were used to determine the associated risk factors. Results Data were analysed from 163 out of 217 eligible patients. Postoperative delirium occurred in one patient (0.6%) and subsyndromal delirium occurred in 19 patients (11.7%). Age ≥ 70 years (odds ratio, [OR] 3.85; 95% confidence interval [CI], 1.36–10.92; p = 0.011) and education level ≤ 9 years (OR, 3.98; 95% CI, 1.39–11.41; p = 0.010) were independent risk factors of subsyndromal delirium after adjusting for preoperative cognitive function. Other pre−/intra-operative variables including anxiety/depression, poor sleep quality, and anaesthesia duration were not associated with subsyndromal delirium. Conclusions In contrast to the low incidence of delirium among patients undergoing curative resection of gastric cancer, a substantial proportion of such patients experienced subsyndromal delirium. Considering the prognostic implications, more careful detection and management of subsyndromal delirium may be warranted in patients with gastric cancer. Electronic supplementary material The online version of this article (10.1186/s12885-018-4681-2) contains supplementary material, which is available to authorized users.

Adjuvant chemotherapy in patients with breast cancer often causes hot flashes, impairing quality of life. However, the chronobiological or psychiatric factors associated with the development of chemotherapy-induced hot flashes (CIHFs) remain undetermined. The purpose of this study was to investigate whether chronotype was associated with the incidence of CIHFs. A total of 119 premenopausal women with non-metastatic breast cancer awaiting adjuvant chemotherapy after surgery without hot flashes were included. The presence of CIHF was defined as having moderate to severe hot flashes, as measured by the subscale of hot flashes in the Menopause Rating Scale, at 4 weeks after the completion of chemotherapy. Chronotype (Morning/Intermediate/Evening) was assessed with the Composite Scale of Morningness before adjuvant chemotherapy. To examine the association between chronotype and CIHF, we built logistic regression models, adjusting for age, body mass index, sleep quality, and radiation therapy. CIHF occurred in 50.4% of participants. Morning type was inversely associated with CIHF (reference: Intermediate type, odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16–0.94; p = 0.040) in the univariate model, and the association remained significant (OR, 0.37; CI, 0.13–0.96; p = 0.045) after adjusting for age, body mass index, sleep quality, and radiation therapy. Morning chronotype is a protective factor against the development of CIHF in patients with breast cancer. Chronotypes should be assessed and considered in the prediction and management of CIHF.

Alcohol consumption exacerbates alcoholic liver disease by attenuating the activity of AMP-activated protein kinase (AMPK). AMPK is activated by fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, and inhibited by direct interaction with cereblon (CRBN), a component of an E3 ubiquitin ligase complex. Based on these preliminary findings, we investigated that CRBN would be up-regulated in the liver by alcohol consumption and that CRBN deficiency would ameliorate hepatic steatosis and pro-inflammatory responses in alcohol-fed mice by increasing AMPK activity. Wild-type, CRBN and PPARα null mice were fed an alcohol-containing liquid diet and administered with fenofibrate. Gene expression profiles and metabolic changes were measured in the liver and blood of these mice. Expression of CRBN, cytochrome P450 2E1 (CYP2E1), lipogenic genes, pro-inflammatory cytokines, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were increased in the Lieber–DeCarli alcohol-challenged mice. Fenofibrate attenuated the induction of CRBN and reduced hepatic steatosis and pro-inflammatory markers in these mice. Ablation of the gene encoding CRBN produced the same effect as fenofibrate. The increase in CRBN gene expression by alcohol and the reduction of CRBN expression by fenofibrate were negated in PPARα null mice. Fenofibrate increased the recruitment of PPARα on CRBN gene promoter in WT mice but not in PPARα null mice. Silencing of AMPK prevented the beneficial effects of fenofibrate. These results demonstrate that activation of PPARα by fenofibrate alleviates alcohol-induced hepatic steatosis and inflammation by reducing the inhibition of AMPK by CRBN. CRBN is a potential therapeutic target for the alcoholic liver disease.

Inflammation has been implicated in the pathogenesis of various cerebral diseases. Thus, control of brain inflammation is regarded as one of the important therapeutic strategies for the treatment of neurodegenerative diseases such as Alzheimer׳s disease and stroke. Isobavachalcone, a flavonoid from Psoralea corylifolia, is known to possess a wide spectrum of biological activities and is expected to be useful in preventing or treating neurodegenerative diseases. However, very little is known regarding its effects on cerebral inflammation. In this study, we examined the effect of isobavachalcone on leukocyte adhesion and intercellular adhesion molecule-1 (ICAM-1) expression in brain endothelial cells activated with lipopolysaccharide (LPS) and explored the possible mechanisms involved. Isobavachalcone significantly down-regulated LPS-induced ICAM-1 expression and leukocyte-endothelial cell adhesion and suppressed NF-κB activity which is implicated in the expression of ICAM-1. It attenuated ICAM-1 expression as well as NF-κB transcriptional activity induced by macrophage-activating lipopeptide 2-kDa (MALP-2) or polyriboinosinic polyribocytidylic acid (poly[I:C]). Isobavachalcone also down-regulated LPS or poly[I:C]-induced expression of IFN-β, which can indirectly activate NF-κB. These data imply that isobavachalcone can modulate both MyD88-dependent and TRIF-dependent signaling of toll-like receptor 4 (TLR4). Taken together, our data suggest that isobavachalcone inhibits LPS-induced ICAM-1 expression and leukocyte adhesion to brain endothelial cell by blocking TLR4 signaling and thus, has the potential to ameliorate neuronal injury in brain diseases associated with inflammation.

Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse reaction caused by chemotherapeutic agents, especially the taxanes. CIPN can persist from months to years after completion of chemotherapy, decreasing quality of life for cancer survivors. The aim of this study was to explore the incidence and risk factors of persistent CIPN among women with breast cancer receiving neoadjuvant chemotherapy. Methods In this prospective study, we recruited women with breast cancer receiving neoadjuvant chemotherapy, including four cycles of docetaxel. Participants reported neuropathic symptoms of tingling/numbness at baseline, at the end of chemotherapy treatment, and at 8 months after completion of chemotherapy. Candidate factors associated with CIPN were assessed before chemotherapy. Results Among 111 participants, 50 (45.0%) experienced CIPN during chemotherapy, and 21 (18.9%) reported persistent CIPN after chemotherapy. Univariate logistic regression analysis revealed that development of CIPN was significantly associated with pre-treatment numbness (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.09–7.40; p = .033), and persistent CIPN was significantly associated with pre-treatment numbness (OR, 3.60; 95% CI, 1.12–11.61; p = .032) and pre-treatment anxiety (OR, 5.02; 95% CI, 1.84–13.70; p = .002). Multivariate analysis indicated that pre-treatment anxiety remained significantly associated with persistent CIPN (OR, 4.01; 95% CI, 1.25–12.87; p = .020). Conclusion Our results suggested that pre-treatment anxiety might be related to a patient's risk for persistent CIPN in women with breast cancer undergoing neoadjuvant chemotherapy. Further research is required to investigate if interventions targeting pre-treatment anxiety could provide prevention and management for persistent CIPN.

Objectives. To investigate the availability of correction of mandibular plane using software for vertical measurements in cone beam computed tomography (CBCT) according to the sites of the mandible.Methods. CBCT scans of six dry mandibles were performed at 0-, 5-, 10-, 15-, and 20-degree angles relative to CBCT scanning table. Using the imaging software, mandibular planes of the different angles were corrected to that of 0-degree angle on the CBCT images. Before and after correction of the mandibular planes, the distance from the mandibular canal to the alveolar crest was measured at M1, M2, and M3 areas of the mandible and vertical measurements were statistically compared with those of 0-angle location using the pairedt-test.Results. Prior to correction, the vertical measurements increased as the angle increased. The greatest differences of measurements were observed in M3 areasP<0.05. After correction, a strong correlation was found in measurements between the 0-degree angle and the other angles in all sites of the mandibleP>0.05.Conclusions. The vertical measurements of CBCT were significantly influenced by mandibular positioning. When CBCT scans are performed at angles other than 0-degree angle, software-based correction of the mandibular plane can be a reliable tool for the accurate vertical measurements in CBCT.

Oxidative stress plays a significant role in the etiology of a variety of neurodegenerative diseases. In this study, we found that Melandrii Herba extract (ME) attenuated oxidative-induced damage in cells. Mechanistically, ME exhibited protection from H2O2-induced neurotoxicity via caspase-3 inactivation, Bcl-2 downregulation, Bax upregulation, and MAPK activation (ERK 1/2, JNK 1/2, and p38 MAPK) in vitro. Moreover, our in vivo data showed that ME was able to attenuate scopolamine-induced cognitive impairment. These results provide in vitro and in vivo evidence that ME exhibits neuroprotective properties against oxidative stress, which suggests that ME is worthy of further investigation as a complementary, or even as an alternative, product for preventing and treating neurodegenerative disorders.

Introduction: Dysregulation of the lipid metabolism has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF);however, the role of free fatty acids (FFA) is not well defined. Aim: to investigate the role of FFA in the pathogenesis in IPF Methods: Fatty acid methyl esters were analyzed with Agilent 7890/5975 Gas Chromatography-Mass Spectrometry and HP-5 MS 30 m * 250 µm * 0.25 µm column (Agilent 19091S-433) in the lung tissues of controls (n=10) and IPF patients (n=10). To evaluate the function of FFA, human lung fibroblasts (MRC-5 cells) were treated with TGF-s1 (5 ng/ml) and/or FFAs including palmitic acid, stearic acid, oleic acid and linoleic acid. Cell viability and protein expression were measured via MTT assay and western blot analysis, respectively. Results: Although the levels of palmitic acid, oleic acid and linoleic acid were elevated, the level of stearic acid was significantly reduced in the lung tissues of patients. Palmitic acid, oleic acid or linoleic acid significantly enhanced the TGF-s1 induced expression of α-smooth muscle actin (SMA) and collagen type-1 in MRC-5 cells;however, stearic acid significantly reduced them. Moreover, palmitic acid and linoleic acid increased the TGF-s1 induced proliferation of MRC-5 cells, but stearic acid decreased it. Stearic acid significantly inhibited the levels of p-Smad2/3 in MRC-5 cells treated with TGF-s1. Conclusion: Our findings suggest that FFAs may have effects on pulmonary fibrosis by regulating TGF-s1 induced activation and proliferation of fibroblasts and be implicated as potential therapeutic targets in IPF.

Background and Purpose 3′‐Sialyllactose (3′‐SL) is a safe compound that is present in high levels in human milk. Although it has anti‐inflammatory properties and supports immune homeostasis, its effect on collagen‐induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3′‐SL on the progression of rheumatoid arthritis (RA) in in vitro and in vivo models. Experimental Approach The anti‐arthritic effect of 3′‐SL was analysed with fibroblast‐like synoviocytes in vitro and an in vivo mouse model of CIA. RT‐PCR, Western blotting and ELISA were performed to evaluate its effects in vitro. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin‐O and haematoxylin staining. Key Results 3′‐SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3′‐SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro‐inflammatory cytokines, https://en.wikipedia.org/wiki/Matrix_metalloproteinases and osteoclastogenesis via NF‐κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF‐κB signalling pathway, was totally blocked by 3′‐SL in the RA models. Conclusions and Implications 3′‐SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated via blockade of the NF‐κB signalling pathway. Therefore, 3′‐SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.