scholarly journals Deleterious Role of Th9 Cells in Pulmonary Fibrosis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3209
Author(s):  
Kui Miao Deng ◽  
Xiang Sheng Yang ◽  
Qun Luo ◽  
Yi Xin She ◽  
Qing Yang Yu ◽  
...  

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. Immune disorders play an important role in IPF pathogenesis. Here, we show that Th9 cells differentiate and activate in the lung tissue of patients with IPF and bleomycin (BLM)-induced lung fibrosis mice. Moreover, we found that Th9 cells promote pulmonary fibrosis in two ways. On the one hand, Th9 cells promote fibroblast differentiation, activation, and collagen secretion by secreting IL-9. On the other hand, they promote differentiation of Th0 cells into Th2 cells by secreting IL-4. Th9 cells and Th2 cells can promote each other, accelerating the Th1/Th2 imbalance and eventually forming a positive feedback of pulmonary fibrosis. In addition, we found that neutralizing IL-9 in both preventive and therapeutic settings ameliorates bleomycin-induced pulmonary fibrosis. Furthermore, we identified several critical signaling pathways involved in the effect of neutralizing IL-9 on pulmonary fibrosis by proteomics study. From an immunological perspective, we elucidated the novel role and underlying mechanism of Th9 cells in pulmonary fibrosis. Our study suggested that Th9-based immunotherapy may be employed as a treatment strategy for IPF.

2021 ◽  
Vol 15 ◽  
pp. 175346662110160
Author(s):  
Timothy N. Perkins ◽  
Tim D. Oury

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease in which most patients die within 3 years of diagnosis. With an unknown etiology, IPF results in progressive fibrosis of the lung parenchyma, diminishing normal lung function, which results in respiratory failure, and eventually, death. While few therapies are available to reduce disease progression, patients continue to advance toward respiratory failure, leaving lung transplantation the only viable option for survival. As incidence and mortality rates steadily increase, the need for novel therapeutics is imperative. The receptor for advanced glycation endproducts (RAGE) is most highly expressed in the lungs and plays a significant role in a number of chronic lung diseases. RAGE has long been linked to IPF; however, confounding data from both human and experimental studies have left an incomplete and perplexing story. This review examines the present understanding of the role of RAGE in human and experimental models of IPF, drawing parallels to recent advances in RAGE biology. Moreover, this review discusses the role of RAGE in lung injury response, type 2 immunity, and cellular senescence, and how such mechanisms may relate to RAGE as both a biomarker of disease progression and potential therapeutic target in IPF. The reviews of this paper are available via the supplemental material section.


2018 ◽  
Vol 12 (2) ◽  
pp. 260-278
Author(s):  
Christoph Demmerling

Abstract The following article argues that fictional texts can be distinguished from non-fictional texts in a prototypical way, even if the concept of the fictional cannot be defined in classical terms. In order to be able to characterize fictional texts, semantic, pragmatic, and reader-conditioned factors have to be taken into account. With reference to Frege, Searle, and Gabriel, the article recalls some proposals for how we might define fictional speech. Underscored in particular is the role of reception for the classification of a text as fictional. I make the case, from a philosophical perspective, for the view that fictional texts represent worlds that do not exist even though these worlds obviously can, and de facto do, contain many elements that are familiar to us from our world. I call these worlds reading worlds and explain the relationship between reading worlds and the life world of readers. This will help support the argument that the encounter with fictional literature can invoke real feelings and that such feelings are by no means irrational, as some defenders of the paradox of fiction would like us to believe. It is the exemplary character of fictional texts that enables us to make connections between the reading worlds and the life world. First and foremost, the article discusses the question of what it is that readers’ feelings are in fact related to. The widespread view that these feelings are primarily related to the characters or events represented in a text proves too simple and needs to be amended. Whoever is sad because of the fate of a fictive character imagines how he or she would fare if in a similar situation. He or she would feel sad as it relates to his or her own situation. And it is this feeling on behalf of one’s self that is the presupposition of sympathy for a fictive character. While reading, the feelings related to fictive characters and content are intertwined with the feelings related to one’s own personal concerns. The feelings one has on his or her own behalf belong to the feelings related to fictive characters; the former are the presupposition of the latter. If we look at the matter in this way, a new perspective opens up on the paradox of fiction. Generally speaking, the discussion surrounding the paradox of fiction is really about readers’ feelings as they relate to fictive persons or content. The question is then how it is possible to have them, since fictive persons and situations do not exist. If, however, the emotional relation to fictive characters and situations is conceived of as mediated by the feelings one has on one’s own behalf, the paradox loses its confusing effect since the imputation of existence no longer plays a central role. Instead, the conjecture that the events in a fictional story could have happened in one’s own life is important. The reader imagines that a story had or could have happened to him or herself. Readers are therefore often moved by a fictive event because they relate what happened in a story to themselves. They have understood the literary event as something that is humanly relevant in a general sense, and they see it as exemplary for human life as such. This is the decisive factor which gives rise to a connection between fiction and reality. The emotional relation to fictive characters happens on the basis of emotions that we would have for our own sake were we confronted with an occurrence like the one being narrated. What happens to the characters in a fictional text could also happen to readers. This is enough to stimulate corresponding feelings. We neither have to assume the existence of fictive characters nor do we have to suspend our knowledge about the fictive character of events or take part in a game of make-believe. But we do have to be able to regard the events in a fictional text as exemplary for human life. The representation of an occurrence in a novel exhibits a number of commonalities with the representation of something that could happen in the future. Consciousness of the future would seem to be a presupposition for developing feelings for something that is only represented. This requires the power of imagination. One has to be able to imagine what is happening to the characters involved in the occurrence being narrated in a fictional text, ›empathize‹ with them, and ultimately one has to be able to imagine that he or she could also be entangled in the same event and what it would be like. Without the use of these skills, it would remain a mystery how reading a fictional text can lead to feelings and how fictive occurrences can be related to reality. The fate of Anna Karenina can move us, we can sympathize with her, because reading the novel confronts us with possibilities that could affect our own lives. The imagination of such possibilities stimulates feelings that are related to us and to our lives. On that basis, we can participate in the fate of fictive characters without having to imagine that they really exist.


Author(s):  
Giovanni Camurati ◽  
Aurélien Francillon ◽  
François-Xavier Standaert

Recently, some wireless devices have been found vulnerable to a novel class of side-channel attacks, called Screaming Channels. These leaks might appear if the sensitive leaks from the processor are unintentionally broadcast by a radio transmitter placed on the same chip. Previous work focuses on identifying the root causes, and on mounting an attack at a distance considerably larger than the one achievable with conventional electromagnetic side channels, which was demonstrated in the low-noise environment of an anechoic chamber. However, a detailed understanding of the leak, attacks that take full advantage of the novel vector, and security evaluations in more practical scenarios are still missing. In this paper, we conduct a thorough experimental analysis of the peculiar properties of Screaming Channels. For example, we learn about the coexistence of intended and unintended data, the role of distance and other parameters on the strength of the leak, the distortion of the leakmodel, and the portability of the profiles. With such insights, we build better attacks. We profile a device connected via cable with 10000·500 traces. Then, 5 months later, we attack a different instance at 15m in an office environment. We recover the AES-128 key with 5000·1000 traces and key enumeration up to 223. Leveraging spatial diversity, we mount some attacks in the presence of obstacles. As a first example of application to a real system, we show a proof-of-concept attack against the authentication method of Google Eddystone beacons. On the one side, this work lowers the bar for more realistic attacks, highlighting the importance of the novel attack vector. On the other side, it provides a broader security evaluation of the leaks, helping the defender and radio designers to evaluate risk, and the need of countermeasures.


2020 ◽  
Author(s):  
Xin Chen ◽  
Liang Yu ◽  
Lijun Chen ◽  
Xiaoqin Zheng ◽  
Lingling Tang ◽  
...  

Abstract Background: The coronavirus disease 2019 (COVID-19) causing a cluster of respiratory infections in Wuhan, China, is identified in December 2019. The main symptoms are defined as fever, cough, shortness of breath, with early symptom of sputum, acute respiratory distress syndrome (ARDS), and the final lung injury and pulmonary fibrosis. Currently, there is no effective method to cure it. Mesenchymal stem cell (MSC) therapy is an immediate need for treating COVID-19 especially severe patients at present.Methods: We describe the two confirmed case of COVID-19 severe patients in Hangzhou, China to explore the role of menstrual blood-derived MSC in the treatment of SARS-CoV-2 infection. Furthermore, we mimic disease model of pulmonary fibrosis in mice to assess the role of MSC. Then, a co-culture system to investigate the underlying mechanism between MSC and pulmonary-associated cells by a series of Physiological, biochemical, bioinformatics analysis.Results: MSC transplantation increases the immune indicators (including lymphocytes) and decreases inflammatory indicators (such as IL-6, IL-10, TNF, and IFN). More importantly, the two patients alleviated symptom and discharged after 3 weeks’ treatment with MSC. Additionally, MSCs exhibit an anti-inflammatory role through suppressing some inflammatory factors (RANTES, GM-CSF, MIG-1g, MCP-5, Eotaxin), which is anastomotic to current clinical study using MSC to treat COVID-19. Conclusions: This is the first report using menstrual blood-derived MSC in treating COVID-19 patients. From our clinical results, we hold one idea that MSCs reduced inflammatory effect to defend cytokine storm. The underlying mechanism is probably that MSCs inhibit epithelia cell apoptosis and reduce the secretion of inflammatory factors to prevent myofibroblasts activity. MSC provides an alternative method for treating COVID-19 particularly some patients with ARDS or subsequent pulmonary fibrosis.Trial registration: This clinical trial was submitted to and approved by the Ethics Committee of the First Affiliated Hospital, Collage of Medicine, Zhejiang University. MSC administration in patient with COVID-19 was conducted in a single center and open-label clinical trial (ChiCTR2000029606).


2020 ◽  
Vol 25 (3) ◽  
pp. 61-66
Author(s):  
Konstantin A. Ozherelyev
Keyword(s):  
New Age ◽  

The paper analyzes the key philosophical contexts and subtexts of M. Shelley’s most famous work “Frankenstein”. According to the author of the article, the philosophical layer of this Gothic novel consists of ideas and maxims that directly inherit the concepts of the worldview platforms of Plato, J.-J. Russo, G. W. F. Hegel, K. F. Volney, W. Godwin, M. Wollstonecraft, as well as the philosophy of the New Age and romanticism. An assumption is made, on the one hand, about the proximity of some worldview attitudes of these philosophers and the author of “Frankenstein” and, on the other hand, about the deliberate introduction of philosophical passages into the fabric of the novel, which play the role of retardation elements.


2020 ◽  
pp. 002198941990052
Author(s):  
Asha Jeffers

David Chariandy’s lauded 2007 debut novel Soucouyant explores the way that immigrants transmit lessons, beliefs, and ways of being to their children both intentionally and unintentionally, and the ways that these transmissions can contradict one another. This article argues that while much of the critical writing about Soucouyant has foregrounded the relationship between the unnamed narrator and his dementia-suffering mother, the text is just as concerned with exploring intragenerational relationships as it is with intergenerational ones. Indeed, the text demonstrates the interweaving of both intergenerational and intragenerational relationships in a unique and compelling way. The lessons that get passed on between the generations shape the lives and interactions of second generation subjects between themselves. In particular, the relationship between the narrator and Meera, the mysterious woman who has moved in with and is taking care of his mother when he returns to her home after deserting her for several years, poses the question of how these two second generation subjects of differing class backgrounds might reconcile themselves with both their parents’ Caribbean pasts, their own Canadian presents, and uncertain futures. The novel’s subtitle, “a novel of forgetting,” signals the central role of memory and forgetting play in the novel. The immigrant parents’ desire and attempts to forget the past are not wholly successful and their second generation children are forced to first remember before they can move forward without being haunted by the traumas, silences, and anxieties of their parents. The complex racial and class politics of Trinidad and Canada lead to the narrator and Meera receiving very different legacies from their parents. However, their eventual coming together, in all its difficulty, suggests that there is hope for second generation subjects who wish to choose a different path than the one set for them by either their parents or the nation-state.


2020 ◽  
Vol 10 (2) ◽  
pp. 182-188
Author(s):  
Kun Gui ◽  
Yu Huang ◽  
Meijin Wang ◽  
Jun Yang

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, resulting in chronic respiratoryfailure and eventually death. β-catenin/Foxo1 showed a protective property in kidney fibrosis, but the role of β-catenin/Foxo1 in IPF was unclear. Our study aimed to investigate the role of β-catenin/Foxo1 in IPF and explore its underlying mechanism. The IPF model was established by injection of bleomycin (BLM) in vivo and stimulation by TGF-β1 in MRC5 cell in vitro. Haematoxylin-eosin staining and Masson’s trichrome staining were performed to examine histopathological injury in lung. Protein expression of corresponding genes was detected using western blot. Immunofluorescence staining assay was carried out to detect the expression of β-catenin, Foxo1, TCF and α-SMA. The expression levels of inflammatory cytokines were determined using ELISA kit assay. The results showed that BLM induced a serious pulmonary injury and proliferated fibroblasts. A higher interaction of β-catenin with TCF and a lower interaction of β-catenin with Foxo1 was found in BLM group compared to the control group. TGF-β1 promoted β-catenin/TCF, whereas ICG-001 inhibited β-catenin/TCF, and promoted β-catenin/Foxo1. Furthermore, ICG-001 reversed TGF-β1 induced largely production of inflammatory cytokines and accumulation of extracellular matrix, as well as high expression of α-SMA. However, AS1842856, a FOXO1 antagonist, strengthened the effects induced by TGF-β1. In summary, our study revealed that β-catenin/Foxo1 protected against IPF through inhibiting inflammatory response and extracellular matrix accumulation, providing an alternative approach to explain the potential mechanism of IPF and seek for more effective therapeutic drugs.


2016 ◽  
Vol 311 (3) ◽  
pp. C508-C517 ◽  
Author(s):  
Hae Jin Kim ◽  
Hae Young Yoo ◽  
Hai Yue Lin ◽  
Goo Taeg Oh ◽  
Yin Hua Zhang ◽  
...  

We previously reported that hypoxia augments α-adrenergic contraction (hypoxic vasoconstriction, HVC) of skeletal arteries in rats. The underlying mechanism may involve hypoxic inhibition of endothelial nitric oxide synthase (eNOS) expressed in skeletal arterial myocytes (16). To further explore the novel role of muscular eNOS in the skeletal artery, we compared HVC in femoral arteries (FAs) from eNOS knockout (KO) mice with that from wild-type (WT) and heterozygous (HZ) mice. Immunohistochemical assays revealed that, in addition to endothelia, eNOS is also expressed in the medial layer of FAs, albeit at a much lower level. However, the medial eNOS signal was not evident in HZ FAs, despite strong expression in the endothelium; similar observations were made in WT carotid arteries (CAs). The amplitude of contraction induced by 1 μM phenylephrine (PhE) was greater in HZ than in WT FAs. Hypoxia (3% Po2) significantly augmented PhE-induced contraction in WT FAs but not in HZ or KO FAs. No HVC was observed in PhE-pretreated WT CAs. The NOS inhibitor nitro-l-arginine methyl ester (0.1 mM) also augmented PhE contraction in endothelium-denuded WT FAs but not in WT CAs. Inhibitors specific to neuronal NOS and inducible NOS did not augment PhE-induced contraction of WT FAs. NADPH oxidase 4 (NOX4) inhibitor (GKT137831, 5 μM), but not NOX2 inhibitor (apocynin, 100 μM), suppressed HVC. Consistent with the role of reactive oxygen species (ROS), HVC was also inhibited by pretreatment with tiron or polyethylene glycol-catalase. Taken together, these data suggest that the eNOS expressed in smooth muscle cells in FAs attenuates α-adrenergic vasoconstriction; this suppression is alleviated under hypoxia, which potentiates vasoconstriction in a NOX4/ROS-dependent mechanism.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Sofia Stefanopoulou ◽  
◽  
Christos-Thomas Kechagias ◽  
Konstantinos D. Malafantis ◽  
◽  
...  

Dystopian fiction is evolving in one of the most interesting literary genres for youth. Education in “Divergent” constitutes a domain of the society which affects directly the citizens and turns to be a catalyst for the establishment of the regime. This article focuses on the role and aspects of education and portrays some representations of the educational system in force in “Divergent”, making possible associations with our social and educational worlds. Using the method of quantitative content analysis, we found that “ranking” and “training” have the most powerful presence in the novel. In this dystopian society, the concept and institution of education has a very different role of the one we would imagine in another more friendly and warless society. Based on our findings, we propose ways in which students can actually learn from dystopian fiction and make steps towards the change of their own educational system and society.


The article analyzes the novel by I. Franco “William Tell” through the prism of musical code and musical ecfrasis. So far, none of the French scholars has paid attention to the plot-forming role of the Rossini’s opera in the short story, but in the first part of the four-part short story the young couple is going to the opera, in the following parts Franco gradually reveals the heroine’s perception of the overture to the opera, and then its individual scenes. After the end of the opera, Olya novelistically unexpectedly, on the external-eventual plane of the novel, declares that she is not in love with Volodko, but on the internal, spiritual and psychological - thanks to the verbal description of the music and its perception by the heroes - this becomes natural. With the help of musical ecfrasis, the depth of Olya’s impression of the Rossini’s opera and the heroine’s psychological sensitivity to what she heard become clear. Moreover, Franco finds his “niche” in the image of the heroine's understanding of opera music: while foreign writers of the mid-19th century most often describe the feelings and emotions that heroes evoke in music, Franco, relying on picture programmability (landscapes of his native land and ideal representations of the heroine about family happiness), which Olya accompanies the heard music, reveals the rich inner world of the girl and her ideals. Rossini’s romantic heroic-patriotic opera “Wilhelm Tell”, her musical images and stage performance become a litmus test in the novel: the relationship of the characters to the opera performance, impressions of it become an important way of revealing their characters. Volodka’s superficial attitude to music as entertainment, on the one hand, and Olya’s ability under the influence of music to see the true meaning of life, correcting her worldview from pastorally romantic to heroic-romantic, on the other hand, make it possible to understand the different life positions of the heroes - the intellectual adaptive Volodka’s service to the people of Olya, and, in fact, the ideological and artistic concept of the writer himself.


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