Association between increased Bcl-2, Fas and FasL levels and inflammation extent in labial salivary glands during primary Sjögren's syndrome

2021 ◽  
Vol 21 ◽  
Author(s):  
Sarah Benchabane ◽  
Assia Slimani-Kaddouri ◽  
Dahbia Acheli ◽  
Thouraya Bendimerad-Iratene ◽  
Redouane Mesbah ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Mononuclear Cells ◽  
Strong Positive Correlation ◽  
Related Factors ◽  
Primary Sjögren Syndrome ◽  
Immunohistochemistry Analysis ◽  
Novel Approach ◽  
Effect Of Therapy ◽  
Chronic Autoimmune Disease

Background: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease characterized by epithelial atrophy, mononuclear infiltration in exocrine glands resulting in defective function of these glands. In pSS, atrophy of the epithelium is caused by an increased amount of apoptosis. Objective: The main aim of this study is to investigate the role of the apoptosis-related factors by studying Bcl-2, Fas and FasL expression in relation to the extent of inflammation as well as the effect of therapy on the expression of these mediators. Methods: In pSS patients (n=62) documented for their serological and clinical features, Fas, FasL and Bcl-2 plasma levels were assessed using enzyme-linked immunosorbent assays. In the same context, we investigated their expression by immunohistochemistry analysis in the labial salivary glands samples in association with the extent of inflammation. Results : Interestingly, our results indicated that in pSS patients, the plasmatic Bcl-2, Fas and FasL levels, which appear to be associated with the severity of inflammation and were significantly elevated in comparison to the healthy controls. Moreover, a significant decrease in all these factors was observed in patients after combined corticosteroids-hydroxychloroquine therapy. Importantly, we report a strong positive correlation between Bcl-2 and NO levels. The immunohistochemical staining reveals a strong Bcl-2 expression in infiltrating mononuclear cells and a total absence in the acinar cells. The Bcl-2 level varies according to the severity of the pathology. However, the expression of Fas and FasL was less important and predominantly localized in infiltrating mononuclear cells. Conclusion: Our current study highlights the involvement of Bcl-2, Fas and FasL in pSS glands injury. These factors may act as useful predictor markers of a clinical course in pSS suggesting a novel approach in the pSS patients monitoring.

scholarly journals Involvement of Aquaporins in the Pathogenesis, Diagnosis and Treatment of Sjögren’s Syndrome

2018 ◽  
Vol 19 (11) ◽  
pp. 3392 ◽  
Author(s):  
Muhammad Soyfoo ◽  
Clara Chivasso ◽  
Jason Perret ◽  
Christine Delporte
Keyword(s):  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Keratoconjunctivitis Sicca ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Chronic Autoimmune Disease ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands resulting in diminished production of saliva and tears. The pathophysiology of SS has not yet been fully deciphered. Classically it has been postulated that sicca symptoms in SS patients are a double step process whereby lymphocytic infiltration of lacrimal and salivary glands (SG) is followed by epithelial cell destruction resulting in keratoconjunctivitis sicca and xerostomia. Recent advances in the field of the pathophysiology of SS have brought in new players, such as aquaporins (AQPs) and anti AQPs autoantibodies that could explain underlying mechanistic processes and unveil new pathophysiological pathways offering a deeper understanding of the disease. In this review, we delineate the link between the AQP and SS, focusing on salivary glands, and discuss the role of AQPs in the treatment of SS-induced xerostomia.

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Transcriptional Activation ◽  
Platinum Resistance ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Platinum Compounds ◽  
Copper Chelation ◽  
Novel Approach ◽  
Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

ROLE OF RETINOL AND TOCOPHEROL IN COMBATING SMOG CAUSED ILLNESS AMONG YOUNG WOMAN

2019 ◽  
Author(s):  
Bisma Laeeque
Keyword(s):  
Case Report ◽  
Vitamin A ◽  
Young Woman ◽  
Good Health ◽  
Health Condition ◽  
Strong Positive Correlation ◽  
Daily Diet ◽  
Food And Nutrition ◽  
Good Health Condition

Retinol and Tocopherol are commonly known as fat soluble Vitamin A and D. This research was undertaken with the objective to study Vitamin A and D’s effect in combating smog caused illness among females. This case report highlights diseases caused among young woman of Lahore due to smog. Hypothesis formulated for this study was accepted after testing that intake of daily-recommended amount of Vitamin A and D by females helps them in fighting diseases caused by smog. An intervention based on Food and Nutrition Board’s Recommended Dietary Allowances (RDAs) was planned. After the analysis of data by SPSS and excel, it was indicated that women could fight smog caused diseases better by including Vitamin A and D in their daily diet. It was also found that a strong positive correlation existed between good health condition among females and intake of Vitamin A and D.

scholarly journals Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321731
Author(s):  
Dominik Aschenbrenner ◽  
Maria Quaranta ◽  
Soumya Banerjee ◽  
Nicholas Ilott ◽  
Joanneke Jansen ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Personalised Medicine ◽  
Mononuclear Phagocytes ◽  
Cytokine Network ◽  
Peripheral Blood Mononuclear ◽  
Transcriptional Signature ◽  
Inflammatory Monocytes ◽  
Transcriptomic Signature ◽  
Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

scholarly journals Home schooling through online teaching in the era of COVID-19: Exploring the role of home-related factors that deepen educational inequalities across European societies

2021 ◽  
pp. 147490412110233
Author(s):  
Kostas Dimopoulos ◽  
Christos Koutsampelas ◽  
Anna Tsatsaroni
Keyword(s):  
Technology Use ◽  
Online Teaching ◽  
Home Schooling ◽  
Information And Communications Technology ◽  
The European Union ◽  
Related Factors ◽  
School Conditions ◽  
Educational Environments ◽  
Teachers And Students

The COVID-19 pandemic has forced governments worldwide to produce solutions to the abruptly interrupted work in education. School systems appear to have responded rapidly, creating home schooling and online educational environments, where teachers and students would interact with safety. In this paper, we attempt a synthesis of Sen’s capability approach, Bourdieu’s theory of capital and Bernstein’s framework in order to theorize the relationships between home and school conditions and practices, and to analyse the data of the 2nd Survey of Schools: ICT in Education (a survey conducted in 2019 on behalf of the European Commission collecting data regarding digitalization in education and digital technologies in learning in the European Union). The survey is complemented by a second set of indicators provided by Eurostat to further investigate the availability and functionality of household space per family in selected European countries. We find significant differences in important social and environmental conversion factors, likely limiting children’s capability to benefit from digital schooling. The most important differences are found in regard to parents’ familiarity with information and communications technology use, while inequalities in environmental factors, such as overcrowded housing, are also existent. Overall, there are large inequalities within and between countries in Europe, which need to be addressed by policymakers.

scholarly journals Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer K. Shaalan ◽  
Tathyane H. N. Teshima ◽  
Abigail S. Tucker ◽  
Gordon B. Proctor
Keyword(s):  
Cell Cycle ◽  
Embryonic Development ◽  
Salivary Glands ◽  
Aurora Kinase ◽  
Serine Threonine Kinase ◽  
Aurora Kinase B ◽  
Development And Differentiation ◽  
Differentiation Marker ◽  
Key Events

AbstractLittle is known about the key molecules that regulate cell division during organogenesis. Here we determine the role of the cell cycle promoter aurora kinase B (AURKB) during development, using embryonic salivary glands (E-SGs) as a model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no previous study has shown its role during organ development. Our previous experiments have highlighted the essential requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs) at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-βgal and p21, respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1. Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis.

scholarly journals Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 766
Author(s):  
David F. Woods ◽  
Stephanie Flynn ◽  
Jose A. Caparrós-Martín ◽  
Stephen M. Stick ◽  
F. Jerry Reen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bile Acids ◽  
Host Response ◽  
Signal Molecules ◽  
Therapeutic Approaches ◽  
Related Factors ◽  
Host Interactions ◽  
Important Host ◽  
Respiratory Microbiota

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis (CF). Understanding the microbial and host-related factors that govern the establishment of chronic CF lung inflammation and pathogen colonisation is essential. Specifically, dissecting the interplay in the inflammation–pathogen–host axis. Bile acids are important host derived and microbially modified signal molecules that have been detected in CF lungs. These bile acids are associated with inflammation and restructuring of the lung microbiota linked to chronicity. This community remodelling involves a switch in the lung microbiota from a high biodiversity/low pathogen state to a low biodiversity/pathogen-dominated state. Bile acids are particularly associated with the dominance of Proteobacterial pathogens. The ability of bile acids to impact directly on both the lung microbiota and the host response offers a unifying principle underpinning the pathogenesis of CF. The modulating role of bile acids in lung microbiota dysbiosis and inflammation could offer new potential targets for designing innovative therapeutic approaches for respiratory disease.

scholarly journals Tumor-Infiltrating CD20+ B Lymphocytes: Significance and Prognostic Implications in Oral Cancer Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 395
Author(s):  
Faustino Julián Suárez-Sánchez ◽  
Paloma Lequerica-Fernández ◽  
Juan Pablo Rodrigo ◽  
Francisco Hermida-Prado ◽  
Julián Suárez-Canto ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Clinical Stage ◽  
Inverse Correlation ◽  
Tumor Infiltrating Lymphocytes ◽  
Immunohistochemical Analysis ◽  
Second Primary ◽  
Strong Positive Correlation ◽  
Related Factors ◽  
Primary Tumors ◽  
Sox2 Expression

Immunohistochemical analysis of stromal/tumoral CD20+ B lymphocytes was performed in 125 OSCC patients. Correlations with immune profiles CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocytes (TILs), tumoral PD-L1, and stem-related factors NANOG and SOX2 were assessed, and also associations with clinical data and patient survival. There was a strong positive correlation between the infiltration of CD20+ B lymphocytes and other immune profiles (i.e., CD4+, CD8+, and FOXP3+ TILs, and CD68+ and CD163+ macrophages) both in stroma and tumor nests. Strikingly, CD20+ TILs were inversely correlated with NANOG/SOX2 expression. Stromal CD20+ TILs were significantly associated with T classification and second primary tumors. A stratified survival analysis showed that tumoral CD20+ TILs were significantly associated with prognosis in male and younger patients, with tobacco or alcohol consumption, high tumoral CD8+ TILs, low tumoral infiltration by CD68+ macrophages, positive PD-L1 expression, and negative NANOG/SOX2. Multivariate Cox analysis further revealed clinical stage and tumoral CD20+ TILs independently associated with disease-specific survival (HR = 2.42, p = 0.003; and HR = 0.57, p = 0.04, respectively). In conclusion, high CD20+ TIL density emerges as an independent good prognostic factor in OSCC, suggesting a role in antitumor immunity. This study also uncovered an inverse correlation between CD20+ TILs and CSC marker expression.

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