Aims/hypothesis
IL-6 is a proinflammatory cytokine associated with the pathogenesis of hepatic diseases. Metformin is an anti-diabetic drug used for the treatment of type 2 diabetes, and orphan ...nuclear receptor small heterodimer partner (SHP, also known as NR0B2), a transcriptional co-repressor, plays an important role in maintaining metabolic homeostasis. Here, we demonstrate that metformin-mediated activation of AMP-activated protein kinase (AMPK) increases SHP protein production and regulates IL-6-induced hepatic insulin resistance.
Methods
We investigated metformin-mediated SHP production improved insulin resistance through the regulation of an IL-6-dependent pathway (involving signal transducer and activator of transcription 3 STAT3 and suppressor of cytokine signalling 3 SOCS3) in both
Shp
knockdown and
Shp
null mice.
Results
IL-6-induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK (Ad-CA-AMPK), and adenoviral SHP (Ad-SHP), but not in
Shp
knockdown, or with the adenoviral dominant negative form of AMPK (Ad-DN-AMPK). Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP) and protein localisation studies showed that SHP inhibits DNA binding of STAT3 on the
Socs3
gene promoter via interaction and colocalisation within the nucleus. Upregulation of inflammatory genes and downregulation of hepatic insulin signalling by acute IL-6 treatment were observed in wild-type mice but not in
Shp
null mice. Finally, chronic IL-6 exposure caused hepatic insulin resistance, leading to impaired insulin tolerance and elevated gluconeogenesis, and these phenomena were aggravated in
Shp
null mice.
Conclusions/interpretation
Our results demonstrate that SHP upregulation by metformin may prevent hepatic disorders by regulating the IL-6-dependent pathway, and that this pathway can help to ameliorate the pathogenesis of cytokine-mediated metabolic dysfunction.
Previously, we have reported that ginsenoside Rg3 has typical activities for neuroprotection and Aβ42 clearance by modulating microglia. In this study, we determined the pivotal role of ginsenoside ...Rg3 in microglia and neuronal cells. In human microglia, Rg3 and its stereoisomers significantly restored inflammatory M1 to normal M0 state and promoted M2 activation by up-regulating acute cytokines such as interleukin-10 and Arginase 1. Moreover, scavenger receptor type A (SRA) was significantly elevated in the presence of ginsenoside Rg3 and 20(S)-Rg3. This indicated that ginsenoside Rg3 could play a crucial role in Aβ uptake and clearance under activated M2 state. We also observed that soluble amyloid precursor protein-alpha (sAPPα) and ADAM10 levels were increased in APP swe-transfected Nuro-2a neuronal cells, whereas sAPPβ was not processed, suggesting that ginsenoside Rg3 was involved in non-amyloidogenic processing. In immunocytochemistry, SRA and a disintegrin and metalloproteinase 10 (desintegrin and metalloproteinase-containing protein 10, ADAM10) were coincidently upregulated in the presence of ginsenoside Rg3 and its stereoisomers compared to those in normal control. Taken together, these results suggested that ginsenoside Rg3 could boost acute activation of microglia, promote Aβ uptake, and elevate the sAPPα processing under activated M2 state. Although in vivo studies need to be performed, it is certain that ginsenoside Rg3 is highly involved in ameliorating the pathogenesis of neurodegeneration and can be a promising candidate for treating Alzheimer's disease as a new therapeutic intervention.
Cryptocurrency: Not far from equilibrium Yi, Eojin; Ahn, Kwangwon; Choi, M.Y.
Technological forecasting & social change,
April 2022, 2022-04-00, 20220401, Letnik:
177
Journal Article
Recenzirano
•The bitcoin market is not consistent with the weak-form efficient market hypothesis.•Yet, it does not differ from other asset categories in terms of its long-term market equilibrium.•A theoretical ...model is provided to explain the puzzle between market efficiency and equilibrium.
The rapid growth and expanding applications of cryptocurrencies are the main factors that have led them to be considered potential assets to investment portfolios. However, the fierce ups-and-downs that Bitcoins have experienced recently, coupled with the extreme volatility in the Bitcoin prices, have cast doubts on the eligibility of cryptocurrencies to be classified as assets. To investigate the characteristics of cryptocurrencies, this study compares Bitcoin, one of the most popular cryptocurrencies, with other major investment assets. Our analysis focuses on the efficient market hypothesis measured by the Hurst exponent, together with long-term market equilibrium measured by Shannon entropy. The findings suggest that although the Bitcoin market is less efficient than other markets, it is not significantly different from the other markets in terms of its long-term market equilibrium. To elucidate these properties, we probe the Fokker–Planck and Schrödinger equations and derive a probability density function, considering the speed of mean reversion and dispersion.
Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe ...psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as ways to prevent and treat these disturbances. An illustrative case vignette is presented describing a patient’s experience of cycles of manic-like behavior and depression while on high-dosage prednisone, with long-term cognitive disorganization, vulnerability to stress, and personality changes. Severe neuropsychiatric consequences (including suicide, suicide attempt, psychosis, mania, depression, panic disorder, and delirium, confusion, or disorientation) have been reported to occur in 15.7 per 100 person-years at risk for all glucocorticoid courses, and 22.2 per 100 person-years at risk for first courses. The majority of patients experience less severe but distressing and possibly persistent changes in mood, cognition, memory, or behavior during glucocorticoid treatment or withdrawal. Although prediction of such effects is difficult, risks vary with age, gender, dosage, prior psychiatric history, and several biological markers. Key mechanisms thought to underlie these risk factors are briefly described. Recommendations are given for identifying individual risk factors and for monitoring and managing adverse neuropsychiatric effects of glucocorticoids.
Background
As Korea has experienced rapid economic development, the lifestyles of Koreans have become more Westernized, in terms of urbanization and dietary habits. Also, the prevalences of allergic ...diseases, such as rhinitis, asthma, and dermatitis, have increased rapidly. This study aimed to identify the factors influencing the symptoms of rhinitis conditions, including rhinitis, allergic rhinitis, overlapped rhinitis, and overlapped allergic rhinitis, among Korean children aged 6–7 years.
Methods
The study subjects were drawn from participants in the International Study of Asthma and Allergies in Childhood (ISAAC) study in 2010 and were aged 6–7 years. We analysed data for a total of 3804 children.
Results
The prevalences of symptoms suggestive of rhinitis and allergic rhinitis in the previous 12 months were 43.4% and 22.1%, respectively. For overlapped rhinitis and overlapped allergic rhinitis, only 2.5% and 1.9% of the children had overlapping symptoms, having rhinitis with asthma and eczema simultaneously. Gender, a parental history of allergic disease, mould or dampness at home, and the risk factors for ‘sick building syndrome’ (SBS) were risk factors influencing rhinitis diseases. In particular, a history of moving to a newly built home in the child's infancy was strongly associated with symptoms of all the rhinitis diseases examined.
Conclusions
This study identified patterns of the prevalence of rhinitis conditions among Korean children that were similar to those reported in Western countries. We confirmed that a history of moving to a newly built home during infancy was associated with a considerable risk of rhinitis conditions.
We report complex phenomena arising among financial analysts, who gather information and generate investment advice, and elucidate them with the help of a theoretical model. Understanding how ...analysts form their forecasts is important in better understanding the financial market. Carrying out big-data analysis of the analyst forecast data from I/B/E/S for nearly thirty years, we find skew distributions as evidence for emergence of complexity, and show how information asymmetry or disparity affects financial analysts' forming their forecasts. Here regulations, information dissemination throughout a fiscal year, and interactions among financial analysts are regarded as the proxy for a lower level of information disparity. It is found that financial analysts with better access to information display contrasting behaviors: a few analysts become bolder and issue forecasts independent of other forecasts while the majority of analysts issue more accurate forecasts and flock to each other. Main body of our sample of optimistic forecasts fits a log-normal distribution, with the tail displaying a power law. Based on the Yule process, we propose a model for the dynamics of issuing forecasts, incorporating interactions between analysts. Explaining nicely empirical data on analyst forecasts, this provides an appealing instance of understanding social phenomena in the perspective of complex systems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Objectives
The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires have shown that the prevalence of childhood asthma is increasing worldwide. Although Asian ...countries used to have lower prevalence rates of allergic disease than Western countries, this prevalence is increasing in several Asian countries. To determine whether the prevalence of childhood asthma is changing in Korean adolescents, we compared findings from nationwide cross‐sectional surveys in 1995 and 2000 on populations of middle‐school children using the Korean version of the ISAAC questionnaire.
Methods
We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 15 481 children, ages 12–15, and encompassing all three grades in middle school, selected from 34 schools across the nation; the response rate was 97.3%. In 2000, 15 894 children were selected from 31 of the same schools, and the response rate was 96.4%. The SAS system version 8.0 was utilized for all statistical analyses.
Results
The WQ showed that the lifetime and 12‐month prevalence of wheeze did not change from 1995 to 2000. While the 12‐month prevalence rates of sleep disturbed by wheezing and night cough increased, the rates of severe attack of wheezing and exercise‐induced wheeze did not change, over this period of time. The lifetime prevalence of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3% in 2000, as did the 12‐month prevalence of asthma treatment, from 1.0% in 1995 to 1.9% in 2000. The AVQ also showed increases in the lifetime and 12‐month prevalence rates of wheeze at rest, exercise‐induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time. These were especially because of significant increases in the Provincial cities of Korea. Interestingly, the 12‐month prevalence of wheeze was consistently high in Cheju with low air pollution indices, whereas this rate was low in Ulsan and Ansan with very high air pollution indices. Risk factor analysis showed that body mass index (BMI), passive smoking, and living with a dog or cat, but not air pollution, were associated with higher risk of wheeze.
Conclusions
In the 5‐year period from 1995 to 2000, the prevalence of asthma symptoms has increased in Korean adolescents, much of it because of increases in Provincial Centers. BMI, passive smoking, and living with a dog or cat are important risk factors. Environmental factors other than air pollution may be associated with increases in asthma, especially in Provincial Centers.
Aims
In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)‐induced allergic rhinitis.
Methods and Results
Oral administration of ...Lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP‐induced allergic rhinitis by reducing airway hyperresponsiveness, and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle‐treated mice, bronchoalveolar lavage fluid and draining lymph node samples from CJLP133 and CJLP243‐administrated mice showed diminished numbers of immune cells, increased secretion of a Th1‐type cytokine (IFN‐γ) and decreased production of Th2‐type cytokines (IL‐4, IL‐5 and IL‐13). Consistent with these results, levels of IL‐4, IL‐5, IL‐13, serum IgE and BP‐specific serum IgG1 were decreased, whereas secretion of IFN‐γ and BP‐specific serum IgG2a was augmented upon administration of CJLP133 and CJLP243 in mice.
Conclusion
Oral administration of L. plantarum CJLP133 and CJLP243 alleviates symptoms of BP‐induced allergic rhinitis in mice by recovering Th1/Th2 balance via enhancement of the Th1‐type immune response.
Significance and Impact of the Study
Lactobacillus plantarum CJLP133 and CJLP243 have therapeutic effects on BP‐induced allergic rhinitis in an animal model.
Following noncurative endoscopic resection of early gastric cancer (EGC), the patient should be observed when the underlying disease is severe, the patient is elderly, or the patient refuses further ...treatment. The aim of this study was to analyze the clinical outcomes of patients with differentiated EGC who underwent noncurative endoscopic resection without additional treatment.
Included patients underwent noncurative endoscopic resection for differentiated EGC without additional treatment at the Asan Medical Center between July 1994 and January 2009. Clinical and oncological outcomes were analyzed.
A total of 159 patients were included in the analysis. The median follow-up period was 33 months (interquartile range IQR 22 - 52 months). In total, 40 patients died (25.2 %) - 3 due to stomach cancer, 34 due to other causes, and 3 from unknown causes; the median survival time after endoscopic treatment for these patients was 27.5 months (IQR 13.8 - 48.3 months). Multivariate analysis showed that the rates of underlying disease (P < 0.001) and lymphovascular invasion (P = 0.005) were higher among the 40 patients who died than among the 119 survivors. The overall 3- and 5-year survival rates were 82.9 % and 77.1 %, respectively; the rates of the patients with lymphovascular invasion were 61.9 % and 42.4 %, respectively, and the rates of patients without lymphovascular invasion were 86.1 % and 81.8 %, respectively (P < 0.001).
Additional treatment provides fewer benefits to patients who do not have long life expectancies. Additional surgery can be considered for patients with lymphovascular invasion because of its high mortality rate; however, the benefits and risks of surgery should be considered carefully.
Background
We have developed the Atopic Dermatitis Symptom Score (ADSS) by which patients or parents can easily assess and record AD symptoms on a daily basis in a smartphone application. The aim of ...this study was to evaluate the reliability and validity of the ADSS.
Methods
We enrolled 307 children and adolescents with AD. Parents or caregivers were asked to record daily symptoms of the patients (itching, sleep disturbance, erythema, dryness, oozing, and edema) using a scale of 0‐4. Statistical analyses consisted of the test‐retest reliability, concurrent validity, minimal clinically important difference (MCID), responsiveness, floor or ceiling effects, and screening accuracy. Receiver‐operating characteristic analyses were conducted to evaluate the ADSS cutoff point for predicting severe AD (SCORing AD SCORAD ≥40).
Results
Test‐retest reliability between daytime and night‐time ADSS was good (intraclass correlation coefficient, 0.82 95% CI: 0.70‐0.90). An increase in ADSS was significantly associated with an increase in SCORAD (r = 0.64, P < .0001) (concurrent validity). The MCID was 4.1 points for the ADSS. There was a significant association between changes in ADSS and SCORAD (r = 0.56, P < .0001), indicating good responsiveness. At the optimal ADSS cutoff value of 7.0, sensitivity, specificity, and positive and negative predictive values were 88.4%, 78.6%, 21.1%, and 99.1%, respectively (screening accuracy).
Conclusions
The ADSS can be a useful tool for self‐assessment of skin symptoms in children with AD.
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