Huntington's disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) ...is a lectin that has not been extensively explored in brain diseases. Herein, we showed that the plasma Gal3 levels of HD patients and mice correlated with disease severity. Moreover, brain Gal3 levels were higher in patients and mice with HD than those in controls. The up-regulation of Gal3 in HD mice occurred before motor impairment, and its level remained high in microglia throughout disease progression. The cell-autonomous up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation through NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 suppressed inflammation, reduced mHTT aggregation, restored neuronal DARPP32 levels, ameliorated motor dysfunction, and increased survival in HD mice. Thus, suppression of Gal3 ameliorates microglia-mediated pathogenesis, which suggests that Gal3 is a novel druggable target for HD.
This study aims to extend the theory of planned behavior (TPB) model to explain people's intentions to engage in energy savings and carbon reduction behaviors that can help mitigate climate change in ...Taiwan. People's moral obligation to perform such pro-environmental behaviors is further considered in the TPB model. The results indicate that the extended TPB model including moral obligation can increase the explanatory power of the original one. In addition to one's attitudes and subjective norm, one's moral obligation to reduce impact on global warming and climate change plays a significant role in predicting one's intentions to engage in energy savings and carbon reduction behaviors to mitigate climate change problems.
•The extended TPB model including moral obligation increases explanatory power.•One's moral obligation plays a significant role in predicting one's intentions.•The strong prediction power of one's moral obligation may weaken or eliminate the impact of one's perceived behavioral control.
This study sought to elucidate the antecedents that may influence the effect of people's purchase behavior on the Earth's sustainable development. It included people's perceived moral obligation and ...sustainability self‐identity in the theory of planned behavior (TPB) model to investigate attitudes among the Taiwanese public's attitude toward purchasing sustainability‐labeled coffee and their purchase intentions. The moderating effect of climate change skepticism is also considered in this study. A total of 745 nationwide and self‐reported questionnaire valid data was collected in Taiwan. Hierarchical and moderated regression analysis results indicated that the components of the TPB model had positive influences on the public's purchase intention. The public's perceived moral obligation and sustainability self‐identity, proposed for inclusion in the TPB model, had significant and positive influences on purchase intention. The extended TPB model has higher explanatory power than that of the original model. The positive relationship between sustainability self‐identity and intention to purchase sustainability‐labeled coffee was moderated by climate change skepticism. This study provides marketers and the players in the supply chain with a comprehensive framework for understanding the influence of perceived moral obligation and sustainability self‐identity on purchase intention toward sustainability‐labeled products. In addition, this study responds to a call for a more thorough investigation of the effect of people's skepticism about climate change in the context of ethical and sustainable consumption decision‐making processes.
Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its ...unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.
Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in ...China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest
National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV
(the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.
The growing knowledge of ferroptosis has suggested the role and therapeutic potential of ferroptosis in cancer, but has not been translated into effective therapy. Liver cancer, primarily ...hepatocellular carcinoma (HCC), is highly lethal with limited treatment options. LIFR is frequently downregulated in HCC. Here, by studying hepatocyte-specific and inducible Lifr-knockout mice, we show that loss of Lifr promotes liver tumorigenesis and confers resistance to drug-induced ferroptosis. Mechanistically, loss of LIFR activates NF-κB signaling through SHP1, leading to upregulation of the iron-sequestering cytokine LCN2, which depletes iron and renders insensitivity to ferroptosis inducers. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. Thus, anti-LCN2 therapy is a promising way to improve liver cancer treatment by targeting ferroptosis.
Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide, yet pharmacotherapies for TBI are currently lacking. Neuroregeneration is important in brain repair and functional ...recovery. In this study, probucol, a cholesterol-lowering drug with established safety profiles, was examined for its therapeutic effects and neuroregenerative actions in TBI.
Male mice were subjected to the controlled cortical impact model of TBI, followed by daily administration of probucol. Neurological and cognitive functions were evaluated. Histological analyses of the neocortex and hippocampus were performed to detect the lesion, dendritic degeneration (microtubule-associated protein 2), synaptic density (synaptophysin), neurogenesis (doublecortin), brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) activation. Involvement of BDNF/TrkB pathway in probucol-mediated effects was examined in primary cultures of cortical neurons.
Probucol reduced brain lesion volume, enhanced the recovery of body symmetry, improved motor function and attenuated memory dysfunction after TBI. Meanwhile, probucol promoted post-injury dendritic growth and synaptogenesis and increased hippocampal proliferating neuronal progenitor cells, along with the formation as well as the survival of newborn neurons. Moreover, probucol enhances BDNF expression and TrkB activation. In vitro, probucol promoted neurite outgrowth, which was inhibited by a selective TrkB antagonist ANA-12.
Probucol enhanced functional restoration and ameliorated cognitive impairment after TBI by promoting post-injury neuronal remodelling and neurogenesis. Increased activation of BDNF/TrkB pathway by probucol, at least in part, contributed to the neuroregenerative effects of probucol. Together, it may be promising to repurpose probucol for TBI.
This study ascertained whether self-efficacy and collective efficacy in the cognitive theory of stress model explains people's self-reported proenvironmental behavior more effectively separately or ...in combination. A questionnaire study was conducted among 707 Taiwanese respondents. The results of structural equation modeling analysis corroborated previous findings that the cognitive theory of stress model can be applied to environmental problems to effectively explain people's self-reported proenvironmental behavior. Moreover, compared with self-efficacy, collective efficacy is a stronger predictor of people's problem-focused coping and self-reported proenvironmental behavior for respondents in this collectivist cultures; failing to include collective efficacy in the cognitive theory of stress model can reduce the power of the model to explain such behavior. The research results regarding the external validation and internal validation of the cognitive theory of stress model were elaborated in this study to more effectively understand people's self-reported proenvironmental behavior.
•This study applied the cognitive theory of stress model to explain people's proenvironmental behavior.•A questionnaire study was conducted among 707 Taiwanese respondents.•Compared to self-efficacy, collective efficacy is a stronger predictor of people's reported proenvironmental behavior.•The intercultural and internal validation of the competing cognitive theory of stress models have been elaborated.
This study aims to develop an extended Theory of Planned Behavior (TPB) research model which includes environmental concern and perceived moral obligation to predict consumers’ intention to visit ...green hotels. A total of 559 respondents collected in Taiwan as data input. The empirical results of structural equation modeling (SEM) indicate that consumers’ environmental concern indeed exert a positive influence on their attitude toward green hotels, subjective norms, and perceived behavioral control (i.e., the antecedents of the TPB model) as well as their perceived moral obligation, which in turn influence their intention to visit green hotels as expected. The results obtained from this empirical study verify that the extended TPB model has a good explanatory power. The implications of the research findings and suggestions for the Taiwan Environmental Protection Administration and the hotel accommodation industry to increase the popularity of green hotels choice are included in the study.
Sorafenib, a multitargeted antiangiogenic tyrosine kinase inhibitor, is the standard of care for patients with advanced hepatocellular carcinoma (HCC). Cumulating evidence suggests that sorafenib ...differentially affects immune cells; however, whether this immunomodulatory effect has any impact on antitumor immune responses is unknown. Using an orthotopic mouse model of HCC and tumor‐free mice, we investigated the effects of sorafenib on antitumor immunity and characterized the underlying mechanisms. Sorafenib treatment inhibited tumor growth and augmented antitumor immune responses in mice bearing established orthotopic HCC. The tumor‐specific effector T cell functions were upregulated, while the proportion of PD‐1‐expressing CD8+ T cells and regulatory T cells (Tregs) was reduced in tumor microenvironment of sorafenib‐treated mice. Mechanistically, the sorafenib‐mediated effects on Tregs could be independent of its direct tumor‐suppressing activities. Sorafenib treatment reduced Treg numbers by inhibiting their proliferation and inducing apoptosis. Moreover, sorafenib inhibited the function of Tregs, characterized by diminished expression of Treg‐associated molecules important for their function and by their impaired suppressive capacity. These data reveal that sorafenib treatment enhanced functions of tumor‐specific effector T cells as well as relieved PD‐1‐mediated intrinsic and Treg‐mediated non‐cell‐autonomous inhibitions in tumor microenvironment leading to effective antitumor immune responses. In addition to the well‐known tumor‐inhibiting activity of sorafenib, its enhancement of antitumor immunity may also contribute to the clinical efficacy. Our findings uncover a previously unrecognized mechanism of action of sorafenib and indicate that sorafenib represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat cancer patients.
What's new?
The tyrosine‐kinase inhibitor sorafenib is thought to slow tumor growth via several mechanisms. However, its effect on immune function has been unclear. In this study using a mouse model of hepatocellular carcinoma (HCC), the authors found that treatment with sorafenib can indeed enhance the anti‐tumor immune response, both by up‐regulating effector T cells and by reducing the number of immune‐suppressive cells in the tumor microenvironment. These results indicate that, in addition to sorafenib's direct anti‐tumor activity, it might also be able to potentiate the efficacy of anti‐tumor immunotherapies in the clinic.
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