scholarly journals Special Issue on “The Tight Junction and Its Proteins: More than Just a Barrier”

2020 ◽  
Vol 21 (13) ◽  
pp. 4612
Author(s):  
Susanne M. Krug ◽  
Michael Fromm
Keyword(s):  
Endothelial Cell ◽  
Tight Junction ◽  
Cell Polarity ◽  
Immune Cells ◽  
Therapeutic Target ◽  
Special Issue ◽  
Cell Sheets ◽  
Cellular Processes ◽  
Long Time ◽  
Surprising Finding

For a long time, the tight junction (TJ) was known to form and regulate the paracellular barrier between epithelia and endothelial cell sheets. Starting shortly after the discovery of the proteins forming the TJ—mainly, the two families of claudins and TAMPs—several other functions have been discovered, a striking one being the surprising finding that some claudins form paracellular channels for small ions and/or water. This Special Issue covers numerous dedicated topics including pathogens affecting the TJ barrier, TJ regulation via immune cells, the TJ as a therapeutic target, TJ and cell polarity, the function of and regulation by proteins of the tricellular TJ, the TJ as a regulator of cellular processes, organ- and tissue-specific functions, TJs as sensors and reactors to environmental conditions, and last, but not least, TJ proteins and cancer. It is not surprising that due to this diversity of topics and functions, the still-young field of TJ research is growing fast. This Editorial gives an introduction to all 43 papers of the Special Issue in a structured topical order.

scholarly journals miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

2018 ◽  
Vol 48 (4) ◽  
pp. 1804-1814 ◽  
Author(s):  
Xing Rong ◽  
Donghui Ge ◽  
Danping Shen ◽  
Xianda Chen ◽  
Xuliang Wang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Kawasaki Disease ◽  
Therapeutic Target ◽  
Umbilical Vein ◽  
Luciferase Reporter ◽  
Endothelial Cell Proliferation ◽  
Cell Functions ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment.

CRISPR–Cas9 gene editing as a tool for developing immunotherapy for cancer

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Gene Editing ◽  
Genetically Engineered ◽  
Cancer Resistance ◽  
Knock Out ◽  
Tumor Tissues ◽  
Engineered T Cells ◽  
Long Time

T cells following genome editing and transformation might be detectable in peripheral blood and tumor tissues for a long time, even more than a year. The types and diversity of T-cells in peripheral blood and tumor tissues changed following transfusion of genetically modified T-cells, and some highly suspected T-cells targeting cancer cells grew, increasing the proportion of such cells. Moreover, after getting genetically engineered T cells, anticancer cytokine secretion increased. T cells changed by gene editing have certain functions, at least from an immunological standpoint. The first clinical research using the CRISPR–Cas9 gene editing method for cancer resistance is more complicated: Using CRISPR–Cas9 gene editing technology to concurrently knock out, amplify, activate and reinfuse three genes in human immune cells. This therapeutic strategy is more demanding, because the changed immune cells have a wider target scope. The data suggest that the efficacy of gene editing in immune cells was 15–45%, and the modified cells could survive long in the peripheral blood and tumor tissues of patients. After three or four months, some T-cells became central T-cells. These encouraging findings pave the way for future experimental cancer research utilizing CRISPR technology.

scholarly journals SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis

2021 ◽  
Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Experimental Verification ◽  
Inflammatory Disease ◽  
Therapeutic Target ◽  
Tyrosine Phosphatase ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Potential Therapeutic Target ◽  
Single Cell Rna Sequencing

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.

scholarly journals Volume 8 Issue 2

2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Karen Nelson ◽  
Tracy Creagh ◽  
John Clarke
Keyword(s):  
Student Persistence ◽  
Peer Review Process ◽  
Professor Emeritus ◽  
Special Issue ◽  
Vincent Tinto ◽  
Theoretical Frameworks ◽  
Long Time ◽  
University Professor ◽  
Practical Experiences ◽  
Conference Committee

This issue is our third Students, Transitions, Achievement, Retention and Success (STARS) Conference special issue held in July this year in Adelaide, Australia.   As is customary, this issue of the journal publishes the top research papers selected via a peer review process and the top Emerging Initiatives selected by the Conference Committee.    We are delighted to feature in this special  issue —Reflections on Student Persistence—prepared by Advisory Board member Professor Vincent Tinto, Distinguished University Professor Emeritus at Syracuse University, USA.  Vincent is a long-time friend and supporter of STARS and its predecessor FYHE Conferences and Journal.   In his article, Vincent explores the case for motivation to be considered as a significant aspect of the tertiary student psyche by drawing on theoretical frameworks, research and practical experiences related to the issue.

scholarly journals Labels and Realities: The Relevance of Terms like ESL and EFL in a Linguistically Complex World

2021 ◽  
Keyword(s):  
Foreign Language ◽  
English Language ◽  
Native Language ◽  
World Englishes ◽  
English Language Teaching ◽  
Complex World ◽  
Special Issue ◽  
Expanding Circle ◽  
Long Time ◽  
Efl Students

For a long time, ELT (‘English language teaching’) scholars and practitioners have used terms like ‘ESL’ (‘English as a second language’) and ‘EFL’ (‘English as a foreign language’) unquestioningly to describe the English used by people outside the so-called ENL (‘English as a native language’) circle. For example, ELT practitioners may conveniently refer to students from places like China, Vietnam and Thailand as EFL students. Interestingly, we find counterparts of such terms in ‘World Englishes’ studies; Braj Kachru’s ‘Inner Circle English’, ‘Outer Circle English’ and ‘Expanding Circle English’ essentially refer to ENL ESL and EFL respectively. Despite the popularity of such terms in scholarly circles, the problems associated with their use have not often been explored in depth. Nevertheless, some authors have described such problems. For example, commenting on the distinction between ESL and EFL, Nayar (1997, p. 10) states, “a great deal of referential fuzziness within the two and denotative overlap between the two are making the terminological distinctions unclear, impractical, and ineffective or, worse still, in some cases inauspicious and irrelevant.” This special issue aims to further examine the use and relevance of these terms.

scholarly journals TRAF3IP2 mediates high glucose-induced endothelin-1 production as well as endothelin-1-induced inflammation in endothelial cells

2018 ◽  
Vol 314 (1) ◽  
pp. H52-H64 ◽  
Author(s):  
Jaume Padilla ◽  
Andrea J. Carpenter ◽  
Nitin A. Das ◽  
Hemanth Kumar Kandikattu ◽  
Susana López-Ongil ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
High Glucose ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Vascular Complications ◽  
Vascular Effects ◽  
Interacting Protein ◽  
Endothelin 1 ◽  
Adapter Molecule

Hyperglycemia-induced production of endothelin (ET)-1 is a hallmark of endothelial dysfunction in diabetes. Although the detrimental vascular effects of increased ET-1 are well known, the molecular mechanisms regulating endothelial synthesis of ET-1 in the setting of diabetes remain largely unidentified. Here, we show that adapter molecule TRAF3 interacting protein 2 (TRAF3IP2) mediates high glucose-induced ET-1 production in endothelial cells and ET-1-mediated endothelial cell inflammation. Specifically, we found that high glucose upregulated TRAF3IP2 in human aortic endothelial cells, which subsequently led to activation of JNK and IKKβ. shRNA-mediated silencing of TRAF3IP2, JNK1, or IKKβ abrogated high-glucose-induced ET-converting enzyme 1 expression and ET-1 production. Likewise, overexpression of TRAF3IP2, in the absence of high glucose, led to activation of JNK and IKKβ as well as increased ET-1 production. Furthermore, ET-1 transcriptionally upregulated TRAF3IP2, and this upregulation was prevented by pharmacological inhibition of ET-1 receptor B using BQ-788, or inhibition of NADPH oxidase-derived reactive oxygen species using gp91ds-tat and GKT137831. Notably, we found that knockdown of TRAF3IP2 abolished ET-1-induced proinflammatory and adhesion molecule (IL-1β, TNF-α, monocyte chemoattractant protein 1, ICAM-1, VCAM-1, and E-selectin) expression and monocyte adhesion to endothelial cells. Finally, we report that TRAF3IP2 is upregulated and colocalized with CD31, an endothelial marker, in the aorta of diabetic mice. Collectively, findings from the present study identify endothelial TRAF3IP2 as a potential new therapeutic target to suppress ET-1 production and associated vascular complications in diabetes. NEW & NOTEWORTHY This study provides the first evidence that the adapter molecule TRAF3 interacting protein 2 mediates high glucose-induced production of endothelin-1 by endothelial cells as well as endothelin-1-mediated endothelial cell inflammation. The findings presented herein suggest that TRAF3 interacting protein 2 may be an important therapeutic target in diabetic vasculopathy characterized by excess endothelin-1 production.

Analysis of DIP2C as a novel regulator for epithelial-mesenchymal transition of rheumatoid arthritis synovium and a potential therapeutic target

Impact ◽  
2021 ◽  
Vol 2021 (8) ◽  
pp. 28-30
Author(s):  
Masao Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Target ◽  
Epithelial Mesenchymal Transition ◽  
Poor Response ◽  
Associate Professor ◽  
Therapeutic Interventions ◽  
Response To Treatment ◽  
Potential Therapeutic Target ◽  
Mesenchymal Transition ◽  
Long Time

Rheumatoid arthritis (RA) is an autoimmune disease that can cause damage to the joints, cartilage and bone. There is no cure but early diagnosis can help mitigate damage. Sometimes RA is particularly difficult to treat, for example when the disease took a long time to be diagnosed. Associate Professor Masao Tanaka, Graduate School of Medicine, Kyoto University, Japan, leads a team of researchers working to improve understanding of the causes of poor response to treatment in RA with a long morbidity. The goal is to restore patients' therapeutic responsiveness, thereby improving outcomes. A previous focus for Tanaka was on a protein called FSTL1. He is now exploring DIP2 as a binding molecule for FSTL1. Other important mechanisms Tanaka is exploring are DNA methylation and the mechanisms of carnitine, which has been found to decrease a variety of activation signalling by inhibiting ceramide production in T cells. He and the team are exploring the involvement of these mechanisms in DIP2. In his most recent investigations, Tanaka is exploring DIP2C as a novel regulator for epithelial-mesenchymal transition of RA synovium and a potential therapeutic target. He is focusing on molecules that are expressed in the cells in joints, making the work directly applicable to RA. The team is carrying out a cohort study called KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) that involves around 2,000 outpatients with RA. Ultimately, Tanaka hopes to identify a reproducible combination of patient conditions and therapeutic interventions that achieve better treatment results for RA patients.

Bacteriophage gene products as potential antimicrobials against tuberculosis

2019 ◽  
Vol 47 (3) ◽  
pp. 847-860 ◽  
Author(s):  
Maria Puiu ◽  
Christina Julius
Keyword(s):  
Phage Therapy ◽  
Basic Research ◽  
Gene Products ◽  
Cellular Processes ◽  
Tb Treatment ◽  
Current State ◽  
Rapid Spread ◽  
Long Time ◽  
State Of Research ◽  
Host Target

Abstract Tuberculosis (TB) is recognised as one of the most pressing global health threats among infectious diseases. Bacteriophages are adapted for killing of their host, and they were exploited in antibacterial therapy already before the discovery of antibiotics. Antibiotics as broadly active drugs overshadowed phage therapy for a long time. However, owing to the rapid spread of antibiotic resistance and the increasing complexity of treatment of drug-resistant TB, mycobacteriophages are being studied for their antimicrobial potential. Besides phage therapy, which is the administration of live phages to infected patients, the development of drugs of phage origin is gaining interest. This path of medical research might provide us with a new pool of previously undiscovered inhibition mechanisms and molecular interactions which are also of interest in basic research of cellular processes, such as transcription. The current state of research on mycobacteriophage-derived anti-TB treatment is reviewed in comparison with inhibitors from other phages, and with focus on transcription as the host target process.

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