scholarly journals Role of Short-wavelength Blue Light in the Formation of Cataract and Expression of Caspase-1, -11 and Gasdermin D in rat Lens Epithelium Cells: Insight into the Novel Pathogenesis of Cataract.

2019 ◽  
Author(s):  
Yamin Wang ◽  
Min Zhang ◽  
Ying Sun ◽  
Xiaohui Wang ◽  
Zhaowei Song ◽  
...  

Abstract Background Cataracts have been verified to be associated with a number of risk factors. The sun and artificial light sources, including light-emitting diode (LED) and fluorescent light tubes, are the primary sources of short-wavelength blue light. With the increasing popularity of blue-rich LED-backlit display devices, our eyes are now exposed to more short-wavelength blue light than they were in the past. The goal of this study was to evaluate the role of short-wavelength blue light in the formation of cataract. Additionally, the pathogenesis of cataracts after short-wavelength light exposure was investigated.Methods SD rats were randomly divided into 2 main groups: a control group (10 rats each for the 4-, 8-, and 12-week groups) and an experimental group (10 rats each for the 4-, 8-, and 12-week groups). The rats in the experimental group were exposed to a short-wavelength blue LED lamp for 12 hours per day. After exposure to the blue LED lamp, the rats were maintained in total darkness for 12 hours, after which a 12-hour light/dark cycle was resumed. The intensity of the lamp was 3000 lux. At the end of the short-wavelength blue LED lamp exposure (for 4, 8, and 12 weeks), the expression levels of caspase-1, caspase-11 and gasdermin D (GSDMD) in rat epithelium cells (LECs) were examined in rat epithelial cells (LECs) using qRT-PCR and Western blotting analyses. Results After 6 weeks, cataracts had developed in the experimental rats (4/20 eyes). The clarity of the lens then gradually worsened with the duration of exposure. Twelve weeks later, all of the rat eyes had developed cataracts. Then the expression levels of caspase-1, caspase-11 and GSDMD at 4, 8, and 12 weeks were significantly higher in samples from rats exposed to a short-wavelength blue LED lamp than samples from control rat (p˂0.05). Conclusion The data indicate that pyroptosis play a key role of in cataracts induced by short-wavelength blue light exposure, highlighting caspase-1, caspase-11 and GSDMD as possible therapeutic targets for cataract treatment. This study might provide new insight into the novel pathogenesis of cataracts.

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.


Author(s):  
Michael Stormly Hansen ◽  
Birgit Sander ◽  
Aki Kawasaki ◽  
Adam Elias Brøndsted ◽  
Claus Nissen

2020 ◽  
Author(s):  
Zhaowei Song ◽  
Xiaohui Wang ◽  
Huazhang Li ◽  
Ying Sun ◽  
Kexin Liu ◽  
...  

Abstract Backgroud: To examine the effects of short-wavelength blue light (SWBL) on cultured human lens epithelial cells (hLECs). The nosogenesis of cataracts after SWBL exposure was discussed. Methods: HLE-B3 hLECs were divided into 3 groups randomly: A: normal control group, which consisted of hLECs cultured in the dark; B: the caspase-1 inhibitor group; and C: the SWBL exposure group. After the SWBL (2500 lux) irradiation (for 8, 16, 24, and 32 h), the caspase-1 and gasdermin D (GSDMD) expression levels in HLE-B3 hLECs were examined using ELISA, immunofluorescence, and Western blotting analyses. Double-positive staining of HLE-B3 hLECs for activated and inhibited caspase-1 was used to confirm pyroptosis in hLECs by flow cytometry. Results: SWBL can cause cell death in HLE-B3 hLECs, but a caspase-1 inhibitor suppressed cell death. The flow cytometry results also confirmed the does-dependent of short-wavelength blue light irradiation on pyroptotic death of hLECs. Caspase-1 and GSDMD expression levels of all hLECs groups changed with short-wavelength blue light exposure times (8, 16, 24, and 32 h) and were higher in groups B and C than group A. The immunofluorescence results demonstrated that the expression of GSDMD-N was higher in the cell membrane in both the B and C groups than in the A group.Conclusion: The data indicate that SWBL induces pyroptotic programmed cell death by activation of the GSDMD signalling axis in HLE-B3 hLECs. These results provide new insights into the exploitation of new candidates for the prevention of cataracts.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Yang ◽  
Zeyang Lin ◽  
Zhaopu Han ◽  
Zhengxin Wu ◽  
Jianyu Hua ◽  
...  

AbstractColorectal cancer (CRC) is a common tumor that harms human health with a high recurrence rate. It has been reported that the expression of microRNA-539 (miR-539) is low in several types of cancer, including CRC. Tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) is highly expressed in CRC and promotes the proliferation, migration and angiogenesis of CRC. However, the relationship between miR-539 and TIPE and the mechanisms by which they regulate the proliferation of CRC remain to be explored. We aimed to investigate the functions and mechanisms of miR-539 in CRC proliferation. Functionally, miR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. Our data reveal the novel role of miR-539 in regulating ferroptosis in CRC via activation of the SAPK/JNK axis, providing new insight into the mechanism of abnormal proliferation in CRC and a novel potential therapeutic target for advanced CRC.


2005 ◽  
Vol 16 (2) ◽  
pp. 73-101 ◽  
Author(s):  
Denise Merkle

Abstract This paper will examine the role of the late-Victorian Lutetian Society translators (Alexander Teixeira de Mattos, their leader, Ernest Dowson, Havelock Ellis, Percy Pinkerton, Victor Plarr, Arthur Symons) as translating subjects and cultural agents, united by the “cause” of providing British readers with unexpurgated translations of some of Émile Zola’s maligned, if not banned, masterpieces so that they might be able to form an unbiased opinion of the literary merits of the works. Furthermore, the paper will explore what motivated these translators to join in this clandestine translation project and try to give some insight into the effect of their (re)translation activity on their personal appreciation of Zola and the novel translated. The paper concludes that the act of (re)translation served to expand the cultural horizons of the Lutetian Society translators. Their translations would, in turn, expand the cultural horizons of those who read them.


2020 ◽  
Vol 10 (5) ◽  
pp. 6444-6459 ◽  

The rapid spread of the novel coronavirus (SARS-CoV-2) as a serious threat to the world public health is in dire need of finding potential therapeutic agents. Chinese have tested several antiviral and antimalarial drugs as potent inhibitors for the novel virus, such as remdesivir, chloroquine, hydroxychloroquine, umifenovir and favipiravir. In this study, we used the molecular docking models to study the binding interactions between these pharmaceuticals, as well as our proposed remdesivir analogue (AZCV-20) with the 3CLpro and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2, using MEO and Autodock4 methods. Our study provides insight into the possible role of structural flexibility and efficacy during interactions between 3CLpro, RdRp and the drugs.


Neophilologus ◽  
2019 ◽  
Vol 104 (1) ◽  
pp. 33-47
Author(s):  
Rozanne Versendaal

AbstractThis article discusses the role of mandements joyeux or joyful writs in the novel Rabelais ressuscité (1611) by the little-known French author Nicolas de Horry. The article first provides insight into the tradition and parodic nature of joyful writs. In a next step, the joyful writs in Horry’s text are identified, and the functions of these parodic passages in the narrative structure of the novel are analysed. Finally, the article demonstrates how an institutional approach to this Early Modern novel, concentrating on the identification of possible readers of the text, can contribute to a better understanding of the critical content of the joyful writs.


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