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Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 180
Author(s):  
Paola Fisicaro ◽  
Carolina Boni

In chronic viral hepatitis and in hepatocarcinoma (HCC), antigen-specific T cells are deeply exhausted, and evidence of dysfunction has also been observed for NK cells, which can play a pathogenetic role, exerting a regulatory activity on adaptive immune responses [...]


2022 ◽  
Vol 36 ◽  
pp. 205873842110212
Author(s):  
Alberto Corrà ◽  
Veronica Bonciolini ◽  
Lavinia Quintarelli ◽  
Alice Verdelli ◽  
Marzia Caproni

Linear IgA bullous dermatosis (LABD) is a mucocutaneous autoimmune blistering disease affecting both adults and children. It is caused by IgA antibodies targeting multiple antigens along the basement membrane zone, leading to disruption of dermoepidermal junction and development of bullous lesions which often presents in characteristic arrangement. Although most LABD cases have been reported to be idiopathic, different triggers have been described, including several drugs and infection. However, the occurrence of vaccine-induced cases of LABD is not widely known and accepted due to the few reports available. We present two cases of LABD occurred following different triggers, rising the suspicion for a possible pathogenetic role of vaccines.


2022 ◽  
pp. 114909
Author(s):  
Yuichi Hattori ◽  
Kohshi Hattori ◽  
Takuji Machida ◽  
Naoyuki Matsuda

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1020-1020
Author(s):  
Noritaka Yada ◽  
Jingrui Sui ◽  
Liang Zheng ◽  
X. Long Zheng

Abstract Introduction. Immune thrombotic thrombocytopenic purpura (iTTP), a potentially fatal blood disorder, is primarily caused by severe deficiency of plasma ADAMTS13 activity resulting from immunoglobulin (Ig) G-mediated inhibition of plasma ADAMTS13 activity. However, severe ADAMTS13 deficiency is necessary but not sufficient to cause acute iTTP. An environmental factor such as infection or acute inflammation may be necessary to trigger the acute onset of the disease. We and others have previously reported that plasma markers of neutrophil activation and neutrophil extracellular traps (NETs) formation are significantly elevated in patients with acute iTTP, which returns to normal during remission. However, the pathogenetic role of NETs in acute iTTP is not fully understood. Methods and results. Using flow cytometry, microfluidic shear-based assay, and confocal imaging analysis, we determined the in vivo NETosis in blood samples obtained from patients with acute episode of iTTP and ex vivo NETs formation, as well as the therapeutic efficacy of DNase I on thrombus formation under flow. We showed that by flow cytometry that only very few CitH3+/MPO+ positive neutrophils were present in the healthy donor blood. This population of cells dramatically increased after being stimulated with a bacterial toxin (i.e., Shigatoxin-2) at ~100 ng/mL for 15 min. Importantly, the number of CitH3+/MPO+ positive neutrophils in the sample obtained from a patient with acute iTTP was ~1,000 times higher than that in the healthy controls (Fig. 1), suggesting a massive NETosis in patients with acute iTTP. Microfluidic shear-based assay and confocal imaging analysis further confirmed a dramatic increase in adhesion and aggregation of murine platelets (stained with Alexa647 anti-CD41) and neutrophil (stained with Hoechst), as well as formation of NETs (stained with Syto green) following a perfusion of an Adamts13 -/- murine whole blood (anti-coagulated with thrombin inhibitor, PPACK) under arterial shear (15 dyne/cm 2) over a stimulated murine endothelial surface. Interestingly, an addition of DNase I (100 U/mL) significantly reduced the overall surface coverage of platelets and neutrophils on the murine endothelial surface under the same conditions (Fig. 2). Conclusions. These results demonstrate for the first time NETosis and NETs formation are common in patients with acute iTTP and in Adamts13 -/- mice after being stimulated with shigatoxin; DNase I appears to be highly efficacious eliminating the NETs and platelet/neutrophil-dominant thrombosis under arterial flow. Our findings support the pathogenetic role of NETs in the onset and progression of iTTP, and the therapeutic potential of DNase I in such a fatal disease. Figure 1 Figure 1. Disclosures Zheng: Alexion: Speakers Bureau; Sanofi-Genzyme: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria; Clotsolution: Other: Co-founder; AJMC: Honoraria.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5518
Author(s):  
Katia Todoerti ◽  
Domenica Ronchetti ◽  
Noemi Puccio ◽  
Ilaria Silvestris ◽  
Vanessa Favasuli ◽  
...  

The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an essential aspect of the investigation, which may contribute to understanding the disease’s complex pathobiology, providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the clinical relevance of the lncRNA MIAT in MM, taking advantage of the publicly available CoMMpass database. MIAT expression in MM is highly heterogeneous and significantly associated with specific molecular lesions frequently occurring in MM. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of MIAT in different signaling pathways and ribosome biogenesis and assembly. These findings suggest that MIAT deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and, indirectly, the translational process. Although MIAT expression levels seem not to be significantly associated with clinical outcome in multivariate analyses, high MIAT expression levels are associated with bortezomib resistance, this suggesting that MIAT targeting could overcome drug resistance in MM. These findings strongly prompt for further studies investigating the significance of MIAT in MM.


2021 ◽  
Vol 27 (4) ◽  
pp. 402-408
Author(s):  
I. V. Gubareva ◽  
Y. Y. Vukolova

Subclinical atherosclerosis is an independent predictor of increased cardiovascular risk, including patients with hypertension. The article provides an overview of the pathogenetic role in atherogenesis and cardiovascular risk stratification of sortilin peptide which belongs to the family of vacuolar sorting receptors of type I. Circulating sortilin impacts both lipid and non-lipid pathogenetic mechanisms of atherogenesis. It can serve as an early biomarker of cardiovascular risk and a potential therapeutic target for dyslipidemia management and atherosclerosis at subclinical level.


Author(s):  
Laura Bosque‐Plata ◽  
Eduardo Pavel Hernández‐Cortés ◽  
Claudia Gragnoli

Itch ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. e51-e51
Author(s):  
Laura L.Y. Hui ◽  
Joyce S.S. Lee ◽  
Hong Liang Tey

2021 ◽  
Vol 22 (16) ◽  
pp. 9000
Author(s):  
Akane Wada ◽  
Yu Sawada ◽  
Hitomi Sugino ◽  
Motonobu Nakamura

Angioedema is a life-threatening emergency event that is associated with bradykinin and histamine-mediated cascades. Although bradykinin-mediated angioedema currently has specific therapeutic options, angioedema is sometimes intractable with current treatments, especially histamine-mediated angioedema, suggesting that some other mediators might contribute to the development of angioedema. Fatty acids are an essential fuel and cell component, and act as a mediator in physiological and pathological human diseases. Recent updates of studies revealed that these fatty acids are involved in vascular permeability and vasodilation, in addition to bradykinin and histamine-mediated reactions. This review summarizes each fatty acid’s function and the specific receptor signaling responses in blood vessels, and focuses on the possible pathogenetic role of fatty acids in angioedema.


Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1294
Author(s):  
Stela Dragomanova ◽  
Simona Miteva ◽  
Ferdinando Nicoletti ◽  
Katia Mangano ◽  
Paolo Fagone ◽  
...  

Oxidative stress (OS), resulting from a disrupted balance between reactive oxygen species (ROS) and protective antioxidants, is thought to play an important pathogenetic role in several diseases, including viral infections. Alpha-lipoic acid (LA) is one of the most-studied and used natural compounds, as it is endowed with a well-defined antioxidant and immunomodulatory profile. Owing to these properties, LA has been tested in several chronic immunoinflammatory conditions, such as diabetic neuropathy and metabolic syndrome. In addition, a pharmacological antiviral profile of LA is emerging, that has attracted attention on the possible use of this compound for the cotreatment of several viral infections. Here, we will review the emerging literature on the potential use of LA in viral infections, including COVID-19.


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