Background/Aims: Macrophages have recently been shown to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanisms remain unclear. Methods: Here, we used an activated lymphocyte-derived DNA (ALD-DNA) method to induce SLE in mice. We used a macrophage-specific eliminator clodronate to selectively deplete macrophages in mice. We isolated macrophages from bone marrow of the mice and used cytokines to differentiate M1 and M2 macrophages, respectively. Adoptive transplantation of M1 or M2 macrophages was performed in clodronate-treated mice. The effects on SLE were evaluated by serum anti-dsDNA autoantibody, by renal pathological changes, and by urine protein levels. Results: ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, by renal pathological changes, and by increases in urine protein levels. Clodronate significantly decreased macrophages in mice, which significantly increased SLE severity. Adoptive transplantation of M2, but not M1 macrophages significantly reduced SLE severity in clodronate- and ALD-DNA-treated mice. Conclusion: M1 and M2 macrophages play different roles in development of SLE. M1 macrophages increase the severity of SLE, while M2 macrophages reduce it. Modulation of macrophage polarity may be an attractive therapy for SLE.
Background So far, there have been no published population studies on the relationship between a COVID-19 infection and public risk perception, information source, knowledge, attitude, and behaviors during the COVID-19 outbreak in China. Objective This study aims to understand the relationships between COVID-19 infection; four personal nonpharmaceutical interventions (NPIs; handwashing, proper coughing habits, social distancing, and mask wearing); and public risk perception, knowledge, attitude, and other social demographic variables. Methods An online survey of 8158 Chinese adults between February 22 and March 5, 2020, was conducted. Bivariate associations between categorical variables were examined using Fisher exact test. We also explored the determinants of four NPIs as well as their association with COVID-19 infection using logistic regression. Results Of 8158 adults included, 57 (0.73%) were infected with COVID-19. The overwhelming majority of respondents showed a positive attitude (n=8094, 99.2%), positive risk perception (n=8146, 99.9%), and high knowledge levels that were among the strongest predictors of the four adopted NPIs (handwashing: n=7895, 96.8%; proper coughing: 5997/6444, 93.1%; social distancing: n=7104/8158, 87.1%; and mask wearing: 5011/5120, 97.9%). There was an increased risk of COVID-19 infection for those who did not wash their hands (2.28% vs 0.65%; risk ratio [RR] 3.53, 95% CI 1.53-8.15; P=.009), did not practice proper coughing (1.79% vs 0.73%; RR 2.44, 95% CI 1.15-5.15; P=.03), did not practice social distancing (1.52% vs 0.58%; RR 2.63, 95% CI 1.48-4.67; P=.002), and did not wear a mask (7.41% vs 0.6%; RR 12.38, 95% CI 5.81-26.36; P<.001). For those who did practice all other three NPIs, wearing a mask was associated with a significantly reduced risk of infection compared to those who did not wear a mask (0.6% vs 16.7%; P=.04). Similarly, for those who did not practice all or part of the other three NPIs, wearing a mask was also associated with a significantly reduced risk of infection. In a penalized logistic regression model including all four NPIs, wearing a mask was the only significant predictor of COVID-19 infection among the four NPIs (odds ratio 7.20, 95% CI 2.24-23.11; P<.001). Conclusions We found high levels of risk perception, positive attitude, desirable knowledge, as well as a high level of adopting the four NPIs. The relevant knowledge, risk perception, and attitude were strong predictors of adapting the four NPIs. Mask wearing, among the four personal NPIs, was the most effective protective measure against COVID-19 infection, with added preventive effect among those who practiced all or part of the other three NPIs.
Brown fat and beige fat are known as thermogenic fat due to their contribution to non-shivering thermogenesis in mammals following cold stimulation. Beige fat is unique due to its origin and its development in white fat. Subsequently, both brown fat and beige fat have become viable targets to combat obesity. Over the last few decades, most therapeutic strategies have been focused on the canonical pathway of thermogenic fat activation via the β3-adrenergic receptor (AR). Notwithstanding, administering β3-AR agonists often leads to side effects including hypertension and particularly cardiovascular disease. It is thus imperative to search for alternative therapeutic approaches to combat obesity. In this review, we discuss the current challenges in the field with respect to stimulating brown/beige fat thermogenesis. Additionally, we include a summary of other newly discovered pathways, including non-AR signaling-and non-UCP1-dependent mechanisms, which could be potential targets for the treatment of obesity and its related metabolic diseases.
The Hippo pathway is an evolutionarily conserved regulator of organ size and tumorigenesis that negatively regulates cell growth and survival. Whether the Hippo pathway regulates cell metabolism is unknown. Here, we report that in the nucleus of hepatocytes, Yes‐associated protein(YAP)—the terminal effector of the Hippo pathway—directly interacts with sterol regulatory element binding proteins (SREBP‐1c and SREBP‐2) on the promoters of the fatty acid synthase (FAS) and 30‐hydroxylmethyl glutaryl coenzyme A reductase (HMGCR), thereby stimulating their transcription and promoting hepatocyte lipogenesis and cholesterol synthesis. In diet‐induced diabetic mice, either Lats1 overexpression or YAP knockdown protects against hepatic steatosis and hyperlipidaemia through suppression of the interaction between YAP and SREBP‐1c/SREBP‐2. These results suggest that YAP is a nuclear co‐factor of SREBPs and that the Hippo pathway negatively affects hepatocyte lipogenesis by inhibiting the function of YAP‐SREBP complexes.
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