Survival of Na ïve T Cells Requires the Expression of Let-7 miRNAs

In this study, we further explored the role of let-7 in peripheral T cell homeostasis. We show that similar to Dicer-deficient mice, let-7-deficient animals develop severe peripheral T cell lymphopenia which appears to be a result of impaired survival due to the low expression of the pro-survival factor Bcl2. In addition, we demonstrate that let-7 controls Bcl2-mediated survival through an IL-7-independent mechanism. Results Peripheral T Cell Lymphopenia in Dicer-Deficient and Lin28Tg Mice Dicer ablation in T cells results in the reduction of mature CD4+ and CD8+ lymphocytes (26) suggesting that RNA interference may have a role in their maintenance. We confirmed this result by analyzing the abundance of T cells using CD4Cre+Dicerfl/fl mice (Figure 1A). The total numbers of CD4+ and especially CD8+ T cell populations in the lymph nodes (LNs) were significantly lower in Dicer-deficient animals in comparison to wild type littermate controls, thus demonstrating that T cell-specific deletion of Dicer leads to T cell lymphopenia in the periphery. To address the question of which particular miRNAs are involved in the control of T cell homeostasis, we focused on the largest family of miRNAs, lethal-7 (let-7). Let-7 is a family of 12 miRNA paralogs in mammals, is expressed in various tissues and is highly conserved throughout evolution (29). Importantly, abundant expression of let-7 miRNAs in naïve T cells is essential to maintain quiescence (28). Altogether, this makes the le...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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ConclusionsPA activates PXR signalling and suppresses NF-κB signalling, consequently causing ameliorating inflammation. Results highlight the importance of PXR–NF-κB crosstalk in colitis and suggest a novel therapeutic reagent.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
We report the case of a 17-year-old patient with recurrent hemorrhagic pericardial effusion, who was diagnosed with primary pericardial fibrosarcoma. However, multiple radiological examinations, including CT and [18F] FDG/PET-CT, suggested the presence of fluid and no sign of tumor. Actually, when a patient presents with recurrent hemorrhagic pericardial effusions, pericardial tumors must be taken into account as part of the differential diagnosis.
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research
We describe a contiguous gene deletion of the ATM locus in a multi-generation family of Italian descent with a strong family history of pancreatic cancer. A deletion of one copy of the entire ATM gene was identified by routine panel testing and further characterized by chromosomal microarray analysis. An 11q22.3 microdeletion of approximately 960kb was identified that is predicted to result in loss of 10 genes including ATM. The deletion was identified in two additional family members including a presymptomatic daughter and an affected sibling. A normal disomic complement of the 11q22.3 region was detected in a third famil...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
ConclusionsHistory of penicillin-associated rash (without angioedema, mucosal ulceration, or systemic involvement), more than 1 year ago, is sufficient to select a patient for a direct oral penicillin challenge. This large multicenter study demonstrates that this approach appears safe, and risk is comparable to that in other procedures being performed in primary care in Australia. The higher risk patients are more likely to benefit from skin testing. This simple risk-based delabeling strategy could potentially be used by nonallergists, leading to more efficient penicillin allergy delabeling service provision.
Source: The Journal of Allergy and Clinical Immunology: In Practice - Category: Allergy & Immunology Source Type: research
ConclusionsThe trial demonstrated a favorable safety profile of the SQ HDM SLIT tablet in Japanese adult patients with AA. The treatment appeared to be efficacious in patients requiring rescue medication (ie, short-acting β2-agonist) at baseline in the efficacy assessment using asthma exacerbation during inhaled corticosteroid reduction (JapicCTI number 121847).
Source: The Journal of Allergy and Clinical Immunology: In Practice - Category: Allergy & Immunology Source Type: research
Publication date: Available online 12 October 2019Source: Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)Author(s): Q. Xu, M. Lv, Y. Xia, Y. Zhao, W. Zhang, Y. ChenAbstractA 42-year-old woman presented with a ten-day history of dysphagia, slight chest pain and occasional vomiting. With the performance of thoracic and abdominal enhanced computed tomography (CT) and upper gastrointestinal contrast, once esophageal cancer was suspected. Significant activity mass in esophagus and mediastinal lymph nodes could be found on the imaging of 18F-FDG PET/CT, which also supported malignancy. However, T...
Source: Revista Espanola de Medicina Nuclear e Imagen Molecular - Category: Nuclear Medicine Source Type: research
CONCLUSIONS IQGAP3 may be a potential target gene for Kaempferol in the treatment of BC, and upregulation of IQGAP3 inhibits Kaempferol-induced apoptosis in BC cells by ERK1/2 signaling activation. Targeting IQGAP3 may contribute to the study of natural phytochemicals as anti-tumor drugs in BC. PMID: 31605603 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
CONCLUSIONS PVT1 exerts an oncogenic role through activating Wnt/ß-catenin signaling in pituitary adenoma cells. The present results may provide a potential therapeutic target or approach for treating pituitary adenomas. PMID: 31604907 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
CONCLUSIONS lncRNA TSLNC8 remarkably inhibited the proliferation and migration and accelerated apoptosis of lung cancer cells by targeting the IL-6/STAT3/HIF-1alpha signaling pathway. TSLNC8 may be a potential therapeutic target for the diagnosis and treatment of NSCLC. PMID: 31601776 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
John SamplesElizabeth Warren ’s presidential campaign has a new Facebook ad claiming Mark Zuckerberg, the CEO of Facebook, has endorsed Donald Trump for re-election. That claim is false, and Warren admits as much in the ad. Warren is not trying to mislead people about Zuckerberg. She is trying to control what can be said on Facebook. That is much more dangerous than any lie appearing in a campaign ad.Recently the Trump campaign ran an ad on Facebook saying former vice president Joe Biden had sought to fire a Ukrainian prosecutor investigating a company whose board included Biden ’s son. Many on the left like Wa...
Source: Cato-at-liberty - Category: American Health Authors: Source Type: blogs
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