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Coenzyme Q0 Inhibits NLRP3 Inflammasome Activation through Mitophagy Induction in LPS/ATP-Stimulated Macrophages
No full text[[abstract]]Coenzyme Q (CoQ) analogs with a variable number of isoprenoid units have exhibited as anti-inflammatory as well as antioxidant molecules. Using novel quinone derivative CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero side chain isoprenoid), we studied its molecular activities against LPS/ATP-induced inflammation and redox imbalance in murine RAW264.7 macrophages. CoQ0’s non- or subcytotoxic concentration suppressed the NLRP3 inflammasome and procaspase-1 activation, followed by downregulation of IL1β expression in LPS/ATP-stimulated RAW264.7 macrophages. Similarly, treatment of CoQ0 led to LC3-I/II accumulation and p62/SQSTM1 activation. An increase in the Beclin-1/Bcl-2 ratio and a decrease in the expression of phosphorylated PI3K/AKT, p70 S6 kinase, and mTOR showed that autophagy was activated. Besides, CoQ0 increased Parkin protein to recruit damaged mitochondria and induced mitophagy in LPS/ATP-stimulated RAW264.7 macrophages. CoQ0 inhibited LPS/ATP-stimulated ROS generation in RAW264.7 macrophages. Notably, when LPS/ATP-stimulated RAW264.7 macrophages were treated with CoQ0, Mito-TEMPO (a mitochondrial ROS inhibitor), or N-acetylcysteine (NAC, a ROS inhibitor), there was a significant reduction of LPS/ATP-stimulated NLRP3 inflammasome activation and IL1β expression. Interestingly, treatment with CoQ0 or Mito-TEMPO, but not NAC, significantly increased LPS/ATP-induced LC3-II accumulation indicating that mitophagy plays a key role in the regulation of CoQ0-inhibited NLRP3 inflammasome activation. Nrf2 knockdown significantly decreased IL1β expression in LPS/ATP-stimulated RAW264.7 macrophages suggesting that CoQ0 inhibited ROS-mediated NLRP3 inflammasome activation and IL1β expression was suppressed due to the Nrf2 activation. Hence, this study showed that CoQ0 might be a promising candidate for the therapeutics of inflammatory disorders due to its effective anti-inflammatory as well as antioxidant properties
從國際與日本法制探討環境權之概念
No full text[[abstract]]臺灣組成份子相當多元，除了原住民族之外，尚有來自於各地之移民與新住民。面對不同族群之文化差異，往往族群間之問題，攸關社會秩序之穩定與發展。為此，如何兼顧不同族群權益，考驗著國家統治正當性的基礎。憲法增修條文第10條第11項明文要求國家「肯定多元文化」，然而於社會發展過程中，相關政策的推動而導致原住民族於生活、經濟與既有文化受到衝擊，甚至因族群偏見或歧視而產生相對剝奪感。面對此等不利處境，如何提昇其社會、經濟地位以符合憲法上肯定多元文化之預設？國家勢必要有更積極之作為。而在保護原住民族之脈絡下，憲法增修條文第10條第12項更要求國家應「保障扶助並促其發展」，進而國家須透過具體建制因應之。考量工作乃促進自立發展之關鍵，因此保障就業即成為維繫原住民族地位並促進其發展之關鍵。然而該如何立論並賦予其正當性？本文藉由「優惠性差別待遇」（Affirmative action）概念進行探討，同時透過釋憲實務見解檢視現行法制相關規定，並從中思考如何強化對其之就業保障，積極落實前開憲法明文之要求。[[abstract]]Equality is the basic Principle guaranteed by the Constitution. If there is a different treatment between races or people, we need to check if the treatment meets the requirement of the principle of equality. Indigenous peoples are equal in dignity and rights to other people. But from their special status, they still need different protection for their development and growth. It's considered that the practice of Indigenous People Employment Rights Protection Act gives advantage to indigenous people; due to the special regulations of the act, which results in the priority for indigenous people on employment. This article focuses on the issue of the right to work for protection of indigenous peoples under the concept of affirmative action. In order to understand the concept, this article observes the theory and constitutional interpretations No. 719. Under the context, it also compares with the development of affirmative action in the United Sates. Through the comparative analysis, this article provides some advice for legislation or law reform in the future
A Static and Dynamic Copula-Based ARIMA-fGARCH Approach to Determinants of Carbon Dioxide Emissions in Argentina. Environmental
No full text[[abstract]]This paper attempts to model both static and dynamic dependence structures and measure impacts of energy consumptions (both renewable (EC) and non-renewable (REN) energies), economic globalization (GLO), and economic growth (GDP) on carbon dioxide (CO2) emissions in Argentina over the period 1970-2020. For analyses purpose, the current research deploys the novel static and dynamic copula-based ARIMA-fGARCH with different submodels. The static bivariate copula results show that the growth rates of the pairs EC-CO2 and GDP-CO2 are asymmetrically positive co-movements and have high left tail (extreme) dependencies, implying that the increase in non-renewable energy and economic growth can critically contribute to the environmental degradation, and the decrease in the consumption of non-renewable energy at a high level will consequently reduce the CO2 emissions at the same level. Based on several copula-based dependence measures, we document that between the two factors, the non-renewable energy has a stronger impact than the economic growth regarding the CO2 emissions. On the other hand, the growth rates of both economic globalization and renewable energy symmetrically negatively co-move with the growth rates of the CO2 emissions, but they have no extreme dependencies, indicating that these factors contribute to Argentina's environmental quality, in which the factor of renewable energy has a greater impact. Furthermore, the dynamic copula outcomes show that the (tail) dependencies of CO2 emissions on the non-renewable energy and economic growth are time-varying, while the pairs REN-CO2 and GLO-CO2 possess only dynamic dependencies, but no dynamic tail dependencies. Moreover, through the dynamic copula-based dependence, the environmental Kuznets curve (EKC) hypothesis can be estimated and illustrated explicitly. In addition, we leverage multivariate vine copulas for modelling dependence structures of the five variables simultaneously, which can reveal rich information regarding conditional associations among the relevant variables. Some policy implications are also provided to mitigate CO2 emissions
Novel contribution of long non-coding RNA MEG3 genotype to prediction of childhood leukemia risk
No full text[[abstract]]Background/aim: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL.
Materials and methods: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL.
Results: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (?3.5 years) and gender (male) was found.
Conclusion: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities
Protective effects of gamma-mangostin on hydrogen peroxide induced cytotoxicity in human retinal pigment epithelial cells
No full text[[abstract]]Background: The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, such as macular degeneration is not well established. This study aimed to evaluate whether treatments with gamma-mangostin can rescue the hydrogen peroxide (H2O2)-induced cytotoxicity in human retinal pigment epithelial (ARPE-19) cells.
Materials and methods: ARPE-19 cells were treated with H2O2 alone or with gamma-mangostin plus H2O2 to investigate changes relating to cell viability, appearance of sub-G1 cells, antioxidant enzymes, and apoptotic-related proteins.
Results: The data showed that under H2O2 treatment of 400 μM, there was a significant decrease in cell viability and enhanced apoptosis, together with an increased expression of Bax, Bad, cleaved-caspase-3, -8, and -9 at the protein level. On the contrary, the protein expression levels of Bcl2 and Bcl-xl were decreased. Gamma-mangostin pre-treatments (2-16 μM) could effectively prevent all alterations.
Conclusion: Gamma-mangostin may conduct its eye-protective effects against H2O2-induced oxidative damage via anti- apoptotic and antioxidant mechanisms in ARPE-19 cells
Renoprotective Effect of Pediococcus Acidilactici GKA4 on Cisplatin?Induced Acute Kidney Injury by Mitigating Inflammation and Oxidative Stress and Regulating the MAPK,AMPK/SIRT1/NF?κB, and PI3K/AKT Pathways.
No full text[[abstract]]Acute kidney injury (AKI) describes a sudden loss of kidney function and is associated with a high mortality. Pediococcus acidilactici is a potent producer of bacteriocin and inhibits the growth of pathogens during fermentation and food storage; it has been used in the food industry for many years. In this study, the potential of P. acidilactici GKA4 (GKA4) to ameliorate AKI was investigated using a cisplatin-induced animal model. First, mice were given oral GKA4 for ten days and intraperitoneally injected with cisplatin on the seventh day to create an AKI mode. GKA4 attenuated renal histopathological alterations, serum biomarkers, the levels of inflammatory mediators, and lipid oxidation in cisplatin-induced nephrotoxicity. Moreover, GKA4 significantly decreased the expression of inflammation-related proteins and mitogen-activated protein kinase (MAPK) in kidney tissues. Eventually, GKA4 also increased the levels of related antioxidant enzymes and pathways. Consistently, sirtuin 1 (SIRT1) upregulated the level of autophagy-related proteins (LC3B, p62, and Beclin1). Further studies are needed to check our results and advance our knowledge of the mechanism whereby PI3K inhibition (wortmannin) reverses the effect of GKA4 on cisplatin-treated AKI. Taken together, GKA4 provides a therapeutic target with promising clinical potential after cisplatin treatment by reducing oxidative stress and inflammation via the MAPK, AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) axes
Measuring China's green economic recovery and energy environment sustainability :Econometric analysis of sustainable development goal
No full text[[abstract]]The purpose of this research is to assess China’s sustainable economic recovery and growth through a comparative analysis of China’s global economy following Covid-19. We use the unit root test and generalized method of moments (GMM) to make inferences. The growth scenario is an important consequence of economic recovery, and the study concludes that increased energy use and rising energy costs need greater funding for the energy industry. Green energy financing is urgently required to offset rising production costs of gas and electricity. It is recommended that both Chinese and global financial institutions, banks and finance ministries, take a prominent role in addressing the crisis. This can be achieved by investing in renewable energy to improve sustainable economic recovery, reduce greenhouse gas (GHG) emissions and accelerate economic recovery. This must be carried out over a long period to achieve the intended results. Strategic development goals (SDGs), such as SDG 7 on clean and cheap energy, and SDG 13 on combating climate change, are urged on all nations in both areas
Asbestos awareness among the residents of St. Kitts and Nevis: a cross-sectional study
No full text[[abstract]]Background
High levels of public awareness regarding the hazards of asbestos, rights to health, and benefits of an asbestos-free country can increase advocacy and political commitment to a total ban on asbestos. We aimed to investigate asbestos awareness and associated sociodemographic characteristics among the adult population of St. Kitts and Nevis.
Methods
In this cross-sectional study, 1009 participants completed an online questionnaire with questions about sociodemographic data and asbestos awareness. We applied multiple regression models to estimate associations between sociodemographic factors, levels of asbestos knowledge, and attitudes toward asbestos management.
Results
We found that 70% of residents of St. Kitts and Nevis considered asbestos exposure to be a general public concern and believed the government should prevent it. Of all participants, 54% were in favor of completely banning the use and importation of all asbestos products and materials; those with higher levels of asbestos knowledge were more likely to favor a total ban. Higher proportions and odds of favoring a total asbestos ban were also observed in participants aged???30 years, women, those with higher education, and those living in St. Kitts (vs. Nevis).
Conclusions
These findings support implementing policies to regulate and outright ban the use of asbestos products and materials in St. Kitts and Nevis. This data can be used to develop tailored campaigns to improve asbestos knowledge among sociodemographic groups with lower asbestos awareness, such as in the wider Caribbean and other under-resourced countries
Impact of chronic hepatitis on cardiovascular events among type 2 diabetes patients in Taiwan pay-for-performance program
No full text[[abstract]]To investigate the impact of chronic hepatitis on cardiovascular events in patients with type 2 diabetes mellitus (T2DM). This nationwide retrospective cohort study included 152,709 adult patients (> 20 years) with T2DM enrolled in the National Health Insurance Diabetes Pay-for-Performance Program from 2008 to 2010 and followed up until the end of 2017. Patients were categorized into groups with hepatitis B, hepatitis C, fatty liver disease, and patients without chronic hepatitis. The incidence of cardiovascular events in patients with T2DM and hepatitis C (79.9/1000 person-years) was higher than that in patients with diabetes combined with other chronic hepatitis, or without chronic hepatitis. After adjusting for confounding factors, T2DM with fatty liver (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.07-1.13) and hepatitis C (adjusted HR: 1.09; 95% CI: 1.03-1.12) demonstrated a significantly higher risk of cardiovascular events. The adjusted visit-to-visit coefficient of variation of HbA1c and fasting blood glucose were associated with a high risk of cardiovascular events (HRs of the highest quartile were 1.05 and 1.12, respectively). Chronic hepatitis affects cardiovascular events in adult patients with T2DM. Glucose variability could be an independent risk factor for cardiovascular events in such patients