scholarly journals HCV poly U/UC sequence–induced inflammation leads to metabolic disorders in vulvar lichen sclerosis

2021 ◽  
Vol 4 (8) ◽  
pp. e202000906
Author(s):  
Qing Cong ◽  
Xiao Guo ◽  
Shengwei Zhang ◽  
Jinhui Wang ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Metabolic Disorders ◽  
Metabolomic Analysis ◽  
Rna Seq ◽  
First Line ◽  
Lichen Sclerosis ◽  
Paired Samples ◽  
Healthy Donors ◽  
Intense Pruritus ◽  
Long Time

Vulvar lichen sclerosis (VLS) is a dermatologic disorder that affects women worldwide. Women with VLS have white, atrophic papules on the vulva. They suffer from life-long intense pruritus. Corticosteroids are the first-line of treatments and the most effective medicines for VLS. Although VLS has been speculated as an autoimmune disease for a long time, its pathogenesis and the molecular mechanism is largely unknown. We performed a comprehensive multi-omics analysis of paired samples from VLS patients as well as healthy donors. From the RNA-seq analysis, we found that VLS is correlated to abnormal antivirus response because of the presence of Hepatitis C Virus poly U/UC sequences. Lipidomic and metabolomic analysis revealed that inflammation-induced metabolic disorders of fatty acids and glutathione were likely the reasons for pruritus, atrophy, and pigment loss in the vulva. Thus, the present study provides an initial interpretation of the pathogenesis and molecular mechanism of VLS and suggests that metabolic disorders that affect the vulva may serve as therapeutic targets for VLS.

scholarly journals Machine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus

2019 ◽  
Author(s):  
William A Figgett ◽  
Katherine Monaghan ◽  
Milica Ng ◽  
Monther Alhamdoosh ◽  
Eugene Maraskovsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Whole Blood ◽  
Rna Seq ◽  
Systemic Lupus ◽  
Disease Heterogeneity ◽  
Healthy Donors

ABSTRACTObjectiveSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that is difficult to treat. There is currently no optimal stratification of patients with SLE, and thus responses to available treatments are unpredictable. Here, we developed a new stratification scheme for patients with SLE, based on the whole-blood transcriptomes of patients with SLE.MethodsWe applied machine learning approaches to RNA-sequencing (RNA-seq) datasets to stratify patients with SLE into four distinct clusters based on their gene expression profiles. A meta-analysis on two recently published whole-blood RNA-seq datasets was carried out and an additional similar dataset of 30 patients with SLE and 29 healthy donors was contributed in this research; 141 patients with SLE and 51 healthy donors were analysed in total.ResultsExamination of SLE clusters, as opposed to unstratified SLE patients, revealed underappreciated differences in the pattern of expression of disease-related genes relative to clinical presentation. Moreover, gene signatures correlated to flare activity were successfully identified.ConclusionGiven that disease heterogeneity has confounded research studies and clinical trials, our approach addresses current unmet medical needs and provides a greater understanding of SLE heterogeneity in humans. Stratification of patients based on gene expression signatures may be a valuable strategy to harness disease heterogeneity and identify patient populations that may be at an increased risk of disease symptoms. Further, this approach can be used to understand the variability in responsiveness to therapeutics, thereby improving the design of clinical trials and advancing personalised therapy.

scholarly journals The urgency of vaccination against Covid-19 in dentists

2021 ◽  
Vol 9 (1) ◽  
pp. e040
Author(s):  
Luis Ernesto Arriola Guillén
Keyword(s):  
Great Risk ◽  
Health Professionals ◽  
Daily Practice ◽  
Target Population ◽  
Health Priorities ◽  
First Line ◽  
Health Organizations ◽  
Risk Levels ◽  
Long Time ◽  
Priority Levels

The requirement of vaccines for the prevention of Covid-19 has become one of the health priorities of different countries worldwide (1, 2). However, most societies still do not have the necessary number of vaccines to cover their entire target population (3, 4). This is especially true in countries that delayed negotiations with the supply companies, and which will, unfortunately, have to wait a long time for the arrival of sufficient quantities to protect their populations. On theother hand, the global vaccination process has established priority levels among its citizens, specifically starting with the so-called first line of action that is health professionals attending Covid-19 patients, due to the great risk to which they are exposed. Additionally, the health organizations of the different countries have proposed to continue the vaccination process according to different criteria, one being the risk levels of the professions. This criterion is aimed at prioritizing professionals most exposed to contagion, but according to their daily practice, what professionals are really the most exposed to contagion?

scholarly journals Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production

2019 ◽  
Vol 8 (11) ◽  
pp. 1859
Author(s):  
Bossennec ◽  
Rodriguez ◽  
Hubert ◽  
Di-Roio ◽  
Machon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Cytokine Production ◽  
Effector T Cells ◽  
First Line ◽  
Healthy Donors ◽  
Regulation Mechanisms ◽  
Ifn Γ ◽  
Cd73 Expression ◽  
Inflammatory Effect

Objectives: Th1.17 are highly polyfunctional, potentially harmful CD4+ effector T cells (Teff) through IFN-γ and IL-17A coproduction. Th1.17 take part in the pathophysiology of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which their hyper activation results in part from defects in negative regulation mechanisms. We recently demonstrated that the ecto-nucleotidase CD73 delineates a Th1.17-enriched Teff population and acts as an endogenous regulatory mechanism. Because Methotrexate (MTX), used as first line treatment of RA and PsA, increases extracellular concentrations of AMP and immunosuppressive adenosine, we investigated the modulation of CD73 by MTX treatment on Teff in RA/PsA patients. Methods: In a prospective cohort of 26 RA and 15 PsA patients before or under MTX treatment, we evaluated CD73 expression on blood Teff subsets, their cytokine production and AMPase functions. Results: We showed a decreased CD73 expression on Th1.17 and Th1 in untreated patients compared to healthy donors that was partly restored under MTX. This decrease in untreated patients leads to a halved Ado production by Th1.17 cells. CD73+ Teff remained functional under MTX treatment, but their CD73 re-expression may contribute to control their activation. Conclusion: Our study unveils uncovered mode of action of MTX on Teff subsets modulation and in the adenosine-dependent termination of inflammation in RA and PsA.

scholarly journals Transcriptome analysis of xa5-mediated resistance to bacterial leaf streak in rice (Oryza sativa L.)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaofang Xie ◽  
Zhiwei Chen ◽  
Binghui Zhang ◽  
Huazhong Guan ◽  
Yan Zheng ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanism ◽  
Oryza Sativa L ◽  
Blast Resistance ◽  
Rna Seq ◽  
Bacterial Leaf Streak ◽  
Wild Type ◽  
Cell Death Pathways ◽  
Rnai Line ◽  
Transgenic Lines

Abstract Bacterial leaf steak (BLS) caused by Xanthomonas oryzae pv. oryzicola (Xoc) is a devastating disease in rice production. The resistance to BLS in rice is a quantitatively inherited trait, of which the molecular mechanism is still unclear. It has been proved that xa5, a recessive bacterial blast resistance gene, is the most possible candidate gene of the QTL qBlsr5a for BLS resistance. To study the molecular mechanism of xa5 function in BLS resistance, we created transgenic lines with RNAi of Xa5 (LOC_Os05g01710) and used RNA-seq to analyze the transcriptomes of a Xa5-RNAi line and the wild-type line at 9 h after inoculation with Xoc, with the mock inoculation as control. We found that Xa5-RNAi could (1) increase the resistance to BLS as expected from xa5; (2) alter (mainly up-regulate) the expression of hundreds of genes, most of which were related to disease resistance; and (3) greatly enhance the response of thousands of genes to Xoc infection, especially of the genes involved in cell death pathways. The results suggest that xa5 is the cause of BLS-resistance of QTL qBlsr5a and it displays BLS resistance effect probably mainly because of the enhanced response of the cell death-related genes to Xoc infection.

Comparative proteomic and metabolomic analysis reveal the antiosteoporotic molecular mechanism of icariin from Epimedium brevicornu maxim

2016 ◽  
Vol 192 ◽  
pp. 370-381 ◽  
Author(s):  
Liming Xue ◽  
Yiping Jiang ◽  
Ting Han ◽  
Naidan Zhang ◽  
Luping Qin ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Metabolomic Analysis

Targeted metabolomic analysis of plasma samples for the diagnosis of inherited metabolic disorders

2012 ◽  
Vol 1226 ◽  
pp. 11-17 ◽  
Author(s):  
Hana Janečková ◽  
Karel Hron ◽  
Petr Wojtowicz ◽  
Eva Hlídková ◽  
Anna Barešová ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Plasma Samples ◽  
Metabolomic Analysis ◽  
Inherited Metabolic Disorders

Proteomic Analysis of Reprograming of Mesenchymal Stem/Stromal Cells (MSC) Following Interferon Gamma Identifies Pathways That Are Upregulated in Suppression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 384-384 ◽  
Author(s):  
Qingdong Guan ◽  
Tanner Shpiruk ◽  
Peyman Ezzati ◽  
Oleg Krokhin ◽  
Scott Gilpin ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Proteomic Analysis ◽  
Conflicts Of Interest ◽  
Mass Spectrometry Data ◽  
Paired Samples ◽  
T Lymphocyte Proliferation ◽  
Healthy Donors ◽  
Ifn Γ ◽  
Postdoctoral Fellowship ◽  
Tandem Mass Spectrometry Data

Abstract Assessing potency of mesenchymal stem/stromal cells (MSC) used for immunologic applications such as the treatment of GVHD or other inflammatory disorders has been a challenge. Expression of PD-L1 or production of indoleamine-pyrrole 2,3-dioxygenase (IDO-1) has been proposed as potential potency markers. To screen for other pathways involved with suppression we undertook proteomic analysis of IFN-γ stimulated MSC. MSC isolated and expanded from normal healthy donors to 70-80% confluence were treated overnight with human rIFN-γ (30ng/ml). MSC were harvested using TrypLE Select and then immunologic and proteomic studies were performed. IFN-γ exposure increased a) MSC expression of IDO-1 and PD-L1, b) MSC suppression of 3rd party T lymphocyte proliferation, c) MSC inhibition of development of IFN-γ producing T lymphocytes, and d) MSC promotion of Treg expansion. Cellular proteomic changes that occur with IFN-γ exposures were studied in paired samples of control and IFN-γ treated MSC. Samples were prepared using a modified Filter Aided Sample Prep (FASP) and digests were separated using 2D liquid chromatography and analysed by tandem mass spectrometry. Data was processed with the Global Proteome Machine and only proteins with at least two confident peptides were reported. A total of 7621 proteins were identified of which 5575 were seen in all samples and 232 proteins were significantly upregulated in the IFN-γ treated cells relative to their controls. The proteomic analysis identified constitutive proteins seen in MSC. The upregulated proteins were significantly enriched (p<10-17) for GO processes such as "response to IFN-γ" and "cytokine mediated signaling pathway". Known inhibitory mediators (such as IDO-1, PD-L1, PGE2, galectin-9) were upregulated. Interestingly adhesion molecules (ICAM-1, VCAM-1, and CCL9) were increased. Other proteins with increased expression include Bone Marrow Stromal 2 (BST2). Conclusion: Proteomic analysis of response of MSC to IFN-γ has identified a signature of proteins upregulated with the activation of immune suppressive functions of MSC. Once confirmed these findings will support the development of a potency test for immunosuppressive potential of given MSC preparations - something that is sorely needed in the clinical manufacturing of MSC products. Acknowledgments: Q.D. is holding a postdoctoral fellowship from MS Society of Canada. This research was supported by The Bihlers' Professorship in Stem Cell Research to D.W. Disclosures No relevant conflicts of interest to declare.

A real-world application of liquid biopsy (LB) in metastatic colorectal cancer (mCRC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 48-48
Author(s):  
Letizia Procaccio ◽  
Marzia Del Re ◽  
Stefania Crucitta ◽  
Giulia Gianfilippo ◽  
Francesca Daniel ◽  
...  
Keyword(s):  
Real World ◽  
False Negative ◽  
Digital Pcr ◽  
Turnaround Time ◽  
Tumor Burden ◽  
First Line ◽  
Specificity And Sensitivity ◽  
Long Time ◽  
Secondary Endpoints ◽  
Tissue Recovery

48 Background: First-line decision making is the key to the successful management of mCRC patients (pts). RAS/BRAF status is essential to choose the best targeted agent. In hub centers, a not negligible proportion of pts referred from elsewhere may not have standard tissue-based (STB) molecular results available at the time of first oncologic visit (T0). LB may help circumvent these hurdles. Methods: A monoinstitutional prospective head-to-head comparison of LB versus (vs) STB testing was conducted in a real-world setting. Selection criteria included: mCRC with unknown RAS/BRAF status at T0, tissue from primary or metastases archived in external centers, no previous anti- EGFR agents. At T0, pts underwent plasma sampling for LB testing and procedure for tissue recovery. RAS/BRAF genotyping was carried out by droplet digital PCR on circulating-free (cf) DNA. Primary endpoint was the comparison of time to LB (T1) vs STB (T2) results. Secondary endpoints were the overall percent agreement (OPA), specificity, sensitivity, positive and negative predictive value (PPV and NPV) of LB. Urinary (u) cfDNA testing was also explored. Results: A total of 33 pts were included. Mean T1 was 7 (2-12) days (d) as compared to 22 (7-65) d mean T2. T2 included a mean time for tissue recovery of 17 d. The OPA between LB and STB analysis was 83%. Compared to STB testing, LB specificity and sensitivity were 90% and 80%, respectively, with a PPV of 94% and NPV of 69%. In detail, at STB and LB testing, RAS mutation was found in 50% and 43% of pts; BRAF mutation in 17% and 13%, respectively. LB results included 1 false positive and 4 false negative (FN). FN showed a significantly lower tumor burden (i.e. total tumor volume) at basal CT scan. Concordance between STB and ucfDNA testing was 89%, with a sensitivity of 83% and specificity of 100% recorded for ucfDNA analysis. Conclusions: Faster turnaround time, high concordance and accuracy are 3 key-points supporting the adoption of LB in routinary mCRC care, in particular when decision on first-line is urgent and tissue recovery from external centers may require a long time. Results should be interpreted with caution in LB wild-type cases with low tumor burden.

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