scholarly journals Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9

2021 ◽  
Vol 22 (23) ◽  
pp. 13064
Author(s):  
Madalena C. Pinto ◽  
Margarida C. Quaresma ◽  
Iris A. L. Silva ◽  
Violeta Railean ◽  
Sofia S. Ramalho ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Disorders ◽  
Cl Secretion ◽  
The Past ◽  
Inflammatory Conditions ◽  
Disease Modifier ◽  
And Function ◽  
The Relationship ◽  
Bronchial Cells ◽  
Constitutively Active

SLC26A9, a constitutively active Cl− transporter, has gained interest over the past years as a relevant disease modifier in several respiratory disorders including Cystic Fibrosis (CF), asthma, and non-CF bronchiectasis. SLC26A9 contributes to epithelial Cl− secretion, thus preventing mucus obstruction under inflammatory conditions. Additionally, SLC26A9 was identified as a CF gene modifier, and its polymorphisms were shown to correlate with the response to drugs modulating CFTR, the defective protein in CF. Here, we aimed to investigate the relationship between SLC26A9 and CFTR, and its role in CF pathogenesis. Our data show that SLC26A9 expression contributes to enhanced CFTR expression and function. While knocking-down SLC26A9 in human bronchial cells leads to lower wt- and F508del-CFTR expression, function, and response to CFTR correctors, the opposite occurs upon its overexpression, highlighting SLC26A9 relevance for CF. Accordingly, F508del-CFTR rescue by the most efficient correctors available is further enhanced by increasing SLC26A9 expression. Interestingly, SLC26A9 overexpression does not increase the PM expression of non-F508del CFTR traffic mutants, namely those unresponsive to corrector drugs. Altogether, our data indicate that SLC26A9 stabilizes CFTR at the ER level and that the efficacy of CFTR modulator drugs may be further enhanced by increasing its expression.

scholarly journals The hypoxia-adenosine link during inflammation

2017 ◽  
Vol 123 (5) ◽  
pp. 1303-1320 ◽  
Author(s):  
Jessica L. Bowser ◽  
Jae W. Lee ◽  
Xiaoyi Yuan ◽  
Holger K. Eltzschig
Keyword(s):  
Myocardial Injury ◽  
Inflammatory Diseases ◽  
Extracellular Adenosine ◽  
Tissue Integrity ◽  
The Past ◽  
Hypoxic Conditions ◽  
Inflammatory Conditions ◽  
Proinflammatory Responses ◽  
Inflammatory Bowel ◽  
The Relationship

Hypoxic tissue conditions occur during a number of inflammatory diseases and are associated with the breakdown of barriers and induction of proinflammatory responses. At the same time, hypoxia is also known to induce several adaptive and tissue-protective pathways that dampen inflammation and protect tissue integrity. Hypoxia-inducible factors (HIFs) that are stabilized during inflammatory or hypoxic conditions are at the center of mediating these responses. In the past decade, several genes regulating extracellular adenosine metabolism and signaling have been identified as being direct targets of HIFs. Here, we discuss the relationship between inflammation, hypoxia, and adenosine and that HIF-driven adenosine metabolism and signaling is essential in providing tissue protection during inflammatory conditions, including myocardial injury, inflammatory bowel disease, and acute lung injury. We also discuss how the hypoxia-adenosine link can be targeted therapeutically in patients as a future treatment approach for inflammatory diseases.

scholarly journals Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 329
Author(s):  
Amal Kouadri ◽  
Johanna Cormenier ◽  
Kevin Gemy ◽  
Laurence Macari ◽  
Peggy Charbonnier ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Inflammatory Responses ◽  
Gene Encoding ◽  
Unfolded Protein ◽  
Intracellular Content ◽  
Key Factor ◽  
Cf Transmembrane Conductance Regulator ◽  
And Function ◽  
Bronchial Cells

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF Transmembrane Conductance Regulator (CFTR), an apical chloride channel. An early inflammation (EI) in the lung of CF patients occurring in the absence of any bacterial infection has been reported. This EI has been proposed to be associated with oxidative stress (OX-S), generated by deregulations of the oxidant/antioxidant status. Recently, we demonstrated that copper (Cu), an essential trace element, mediates OX-S in bronchial cells. However, the role of this element in the development of CF-EI, in association with OX-S, has never been investigated. Using healthy (16HBE14o-; HBE), CF (CFBE14o-; CFBE), and corrected-wild type CFTR CF (CFBE-wt) bronchial cells, we characterized the inflammation and OX-S profiles in relation to the copper status and CFTR expression and function. We demonstrated that CFBE cells exhibited a CFTR-independent intrinsic inflammation. These cells also exhibited an alteration in mitochondria, UPR (Unfolded Protein Response), catalase, Cu/Zn- and Mn-SOD activities, and an increase in the intracellular content of iron, zinc, and Cu. The increase in Cu concentration was associated with OX-S and inflammatory responses. These data identify cellular Cu as a key factor in the generation of CF-associated OX-S and opens new areas of investigation to better understand CF-associated EI.

Neonatal Microbiome and the Gut–Brain Axis: Is It the Origin of Adult Diseases?

2018 ◽  
Vol 17 (03) ◽  
pp. 095-104
Author(s):  
Yssra S. Soliman ◽  
Islam T. Elkhateb ◽  
Hany Z. Aly
Keyword(s):  
Normal Structure ◽  
Structure And Function ◽  
Chronic Illnesses ◽  
The Past ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System ◽  
Irritable Bowel ◽  
And Function ◽  
Relationship Of ◽  
The Relationship

AbstractThe gut–brain axis may contribute to the pathophysiology of a variety of neuropsychiatric diseases and chronic illnesses of adulthood. A literature search was completed using PubMed and the following keywords: “gut microbiota,” “breast milk,” “schizophrenia,” “irritable bowel syndrome,” “obesity,” “anorexia and bulimia nervosa,” and “depression.” The search was limited to articles available in English and published in the past 20 years. The human microbiota is essential to normal structure and function. The relationship of microbiota and the central nervous system is called the gut–brain axis, which may be responsible for many pathologic conditions. Research is needed to confirm this association and unveil the pathogenesis of this phenomenon.

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

Scanning tunneling microscopy (STM) of DNA and RNA

1989 ◽  
Vol 47 ◽  
pp. 34-35
Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans
Keyword(s):  
Molecular Structures ◽  
Inorganic Materials ◽  
Resolving Power ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Form And Function ◽  
Dna And Rna ◽  
Calf Thymus ◽  
And Function ◽  
The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

Poor Acceptance of the Past is Related to Depressive Symptoms in Older Adults

GeroPsych ◽  
2020 ◽  
Vol 33 (4) ◽  
pp. 246-251
Author(s):  
Gozde Cetinkol ◽  
Gulbahar Bastug ◽  
E. Tugba Ozel Kizil
Keyword(s):  
Older Adults ◽  
Regression Analysis ◽  
Depressive Symptoms ◽  
Death Anxiety ◽  
Geriatric Depression ◽  
Ego Integrity ◽  
The Past ◽  
Depressed Group ◽  
Total Death ◽  
The Relationship

Abstract. Depression in older adults can be explained by Erikson’s theory on the conflict of ego integrity versus hopelessness. The study investigated the relationship between past acceptance, hopelessness, death anxiety, and depressive symptoms in 100 older (≥50 years) adults. The total Beck Hopelessness (BHS), Geriatric Depression (GDS), and Accepting the Past (ACPAST) subscale scores of the depressed group were higher, while the total Death Anxiety (DAS) and Reminiscing the Past (REM) subscale scores of both groups were similar. A regression analysis revealed that the BHS, DAS, and ACPAST predicted the GDS. Past acceptance seems to be important for ego integrity in older adults.

ICM is sensitive to detect potentiation of CFTR-mediated Cl- secretion in patients with cystic fibrosis and the G551D mutation treated with ivacaftor

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
SY Graeber ◽  
MJ Hug ◽  
O Sommerburg ◽  
JG Mainz ◽  
J Hentschel ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cl Secretion

A literature review on firms' internationalisation through e-commerce

2019 ◽  
pp. 121-143
Author(s):  
Riccardo Resciniti ◽  
Federica De Vanna
Keyword(s):  
Systematic Review ◽  
Literature Review ◽  
International Business ◽  
Decision Process ◽  
Foreign Markets ◽  
New Markets ◽  
Integrative Framework ◽  
The Past ◽  
The Relationship

The rise of e-commerce has brought considerable changes to the relationship between firms and consumers, especially within international business. Hence, understanding the use of such means for entering foreign markets has become critical for companies. However, the research on this issue is new and so it is important to evaluate what has been studied in the past. In this study, we conduct a systematic review of e-commerce and internationalisation studies to explicate how firms use e-commerce to enter new markets and to export. The studies are classified by theories and methods used in the literature. Moreover, we draw upon the internationalisation decision process (antecedents-modalities-consequences) to propose an integrative framework for understanding the role of e-commerce in internationalisation

Policy Making Introduction

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Nina TERREY ◽  
Sabine JUNGINGER
Keyword(s):  
Policy Implementation ◽  
Policy Making ◽  
Creative Industries ◽  
Design Management ◽  
Support Design ◽  
The Past ◽  
Academic Researchers ◽  
Design Activities ◽  
The Relationship ◽  
Professional Impact

The relationship that exists between design, policies and governance is quite complex and presents academic researchers continuously with new opportunities to engage and explore aspects relevant to design management. Over the past years, we have witnessed how the earlier focus on developing policies for design has shifted to an interest in understanding the ways in which design contributes to policy-making and policy implementation. Research into policies for design has produced insights into how policy-making decisions can advance professional impact and opportunities for designers and the creative industries. This research looked into how design researchers and design practitioners themselves can benefit from specific policies that support design activities and create the space for emerging design processes.

Kedudukan dan Fungsi Bahasa dalam Permuseuman

Metahumaniora ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 54
Author(s):  
Erlina Zulkifli Mahmud ◽  
Taufik Ampera ◽  
Yuyu Yohana Risagarniwa ◽  
Inu Isnaeni Sidiq
Keyword(s):  
Human Life ◽  
Field Research ◽  
Communicative Function ◽  
Language Functions ◽  
The Past ◽  
Library Research ◽  
History Of ◽  
And Function ◽  
Museum Guides ◽  
Bahasa Indonesia

Kedudukan dan fungsi bahasa sebagai alat komunikasi manusia mencakup seluruh bidang kehidupan termasuk ilmu pengetahuan antara lain terkait sejarah peradaban manusia; bagaimana manusia mempertahankan hidupnya, bagaimana manusia memperlakukan alam, bagaimana alam menyediakan segala kebutuhan manusia. Apa yang dilakukan manusia saat ini, saat lampau, dan apa yang dilakukan manusia jauh di masa prasejarah, bagaimana kondisi alam di masa-masa tersebut, apa perubahan dan perkembangannya, dapat didokumentasikan melalui bahasa, divisualisasikan kembali, lalu dipajang sebagai salah satu upaya konversai dan preservasi dalam satu institusi yang disebut museum. Penelitian ini membahas kedudukan dan fungsi bahasa dalam permuseuman. Bagaimana kedudukan dan fungsi bahasa dalam permuseuman baik dalam informasi yang disampaikan oleh pemandu wisata museumnya maupun yang terpajang menyertai benda-benda dan gambar-gambar merupakan tujuan dari penelitian ini. Metode penelitian yang digunakan adalah gabungan antara metode lapangan dan metode literatur. Hasil penelitian menunjukkan bahwa secara umum kedudukan bahasa Indonesia berada pada urutan pertama setelah Bahasa Inggris dan keberadaan kedua bahasa dalam permuseuman ini melibatkan dua fungsi utama bahasa, yakni fungsi komunikatif dan fungsi informatif.The existence and function of language  as a medium of communication covers all fields of human life including knowledge, one of them is the history of human civilization; how humans survived, how human utilized nature for their lives, and how nature provides all the necessities for humans. What humans have been doing now, what they have done in the past and far before that in the pre-history time, how the conditions of the nature at those times were and what changes as well as progresses occurred are documented using language, then re-visualized,  displayed as one of conservation and preservation acts in an institution called museum. This research discusess the existence and function of language in museums. How important the existence of a language in museums and what language functions used in museums both in informations given by the museum guides and on the displays accompanying objects and pictures are the aims of this research. The methods used are the combination between field research and library research. The results show that generally the existence of Indonesian language plays more important role than English and both languages have two main functions; communicative function and informative function.     

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