Search results for "aRR"
showing 10 items of 10185 documents
Fungal Deoxynivalenol-Induced Enterocyte Distress Is Attenuated by Adulterated Adlay: In Vitro Evidences for Mucoactive Counteraction
2018
Adlay is a cereal crop that has long been used as traditional herbal medicine and as a highly nourishing food. However, deoxynivalenol (DON), the most prevalent trichothecene mycotoxin worldwide, frequently spoils grains, including adlay, via fungal infection. On the basis of an assumption that the actions of DON in the gut could be modified by adlay consumption, we simulated the impacts of co-exposure in enterocytes and investigated the effectiveness of treatment with adlay for reducing the risk of DON-induced inflammation and epithelia barrier injury. In particular, adlay suppressed DON-induced pro-inflammatory signals such as mitogen-activated kinase transduction and the epidermal growth…
The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery
2018
Nanocarriers (NC) are very promising tools for cancer immunotherapy. Whereas conventional vaccines are based on the administration of an antigen and an adjuvant in an independent fashion, nanovaccines can facilitate cell-specific co-delivery of antigen and adjuvant. Furthermore, nanovaccines can be decorated on their surface with molecules that facilitate target-specific antigen delivery to certain antigen-presenting cell types or tumor cells. However, the target cell-specific uptake of nanovaccines is highly dependent on the modifications of the nanocarrier itself. One of these is the formation of a protein corona around NC after in vivo administration, which may potently affect cell-speci…
Vγ9Vδ2 T Cells in the Bone Marrow of Myeloma Patients: A Paradigm of Microenvironment-Induced Immune Suppression
2018
Vγ9Vδ2 T cells are non-conventional T cells with a natural inclination to recognize and kill cancer cells. Malignant B cells, including myeloma cells, are privileged targets of Vγ9Vδ2 T cells in vitro. However, this inclination is often lost in vivo due to multiple mechanisms mediated by tumor cells and local microenvironment. Multiple myeloma (MM) is a paradigm disease in which antitumor immunity is selectively impaired at the tumor site. By interrogating the immune reactivity of bone marrow (BM) Vγ9Vδ2 T cells to phosphoantigens, we have revealed a very early and long-lasting impairment of Vγ9Vδ2 T-cell immune functions which is already detectable in monoclonal gammopathy of undetermined …
The Ontogeny of Monocyte Subsets
2019
Classical and non-classical monocytes, and the macrophages and monocyte-derived dendritic cells they produce, play key roles in host defense against pathogens, immune regulation, tissue repair and many other processes throughout the body. Recent studies have revealed previously unappreciated heterogeneity among monocytes that may explain this functional diversity, but our understanding of mechanisms controlling the functional programming of distinct monocyte subsets remains incomplete. Resolving monocyte heterogeneity and understanding how their functional identity is determined holds great promise for therapeutic immune modulation. In this review, we examine how monocyte origins and develo…
Localized Interleukin-12 for Cancer Immunotherapy
2020
Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as a potential immunotherapy for cancer. Unfortunately, IL-12's remarkable antitumor efficacy in preclinical models has yet to be replicated in humans. Early clinical trials in the mid-1990's showed that systemic delivery of IL-12 incurred dose-limiting toxicities. Nevertheless, IL-12's pleiotropic activity, i.e., its ability to engage multiple effector mechanisms and reverse tumor-induced immunosuppression, continues to entice cancer researchers. The development of strategies which maximize IL-12 delivery to the tumor microenvironment while minimizing systemic exposure are of increasing interest…
Gamma-Delta CAR-T Cells Show CAR-Directed and Independent Activity Against Leukemia
2020
Autologous T cells engineered to express a chimeric antigen receptor (CAR) against the CD19 antigen are in the frontline of contemporary hemato-oncology therapies, leading to high remission rates in B-cell malignancies. Although effective, major obstacles involve the complex and costly individualized manufacturing process, and CD19 target antigen loss or modulation leading to resistant and relapse following CAR therapy. A potential solution for these limitations is the use of donor-derived γδT cells as a CAR backbone. γδT cells lack allogenecity and are safely used in haploidentical transplants. Moreover, γδT cells are known to mediate natural anti-tumor responses. Here, we describe a 14-da…
Dynamics of a Protein Interaction Network Associated to the Aggregation of polyQ-Expanded Ataxin-1
2020
Background: Several experimental models of polyglutamine (polyQ) diseases have been previously developed that are useful for studying disease progression in the primarily affected central nervous system. However, there is a missing link between cellular and animal models that would indicate the molecular defects occurring in neurons and are responsible for the disease phenotype in vivo. Methods: Here, we used a computational approach to identify dysregulated pathways shared by an in vitro and an in vivo model of ATXN1(Q82) protein aggregation, the mutant protein that causes the neurodegenerative polyQ disease spinocerebellar ataxia type-1 (SCA1). Results: A set of common dysregulated pathwa…
Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology
2020
Bone remodeling is uncoupled in the multiple myeloma (MM) bone marrow niche, resulting in enhanced osteoclastogenesis responsible of MM-related bone disease (MMBD). Several studies have disclosed the mechanisms underlying increased osteoclast formation and activity triggered by the various cellular components of the MM bone marrow microenvironment, leading to the identification of novel targets for therapeutic intervention. In this regard, recent attention has been given to non-coding RNA (ncRNA) molecules, that finely tune gene expression programs involved in bone homeostasis both in physiological and pathological settings. In this review, we will analyze major signaling pathways involved …
MARTX Toxin in the Zoonotic Serovar of Vibrio vulnificus Triggers an Early Cytokine Storm in Mice
2017
Vibrio vulnificus biotype 2-serovar E is a zoonotic clonal complex that can cause death by sepsis in humans and fish. Unlike other biotypes, Bt2 produces a unique type of MARTXVv (Multifunctional-Autoprocessive-Repeats-in-Toxin; RtxA13), which is encoded by a gene duplicated in the pVvBt2 plasmid and chromosome II. In this work, we analyzed the activity of this toxin and its role in human sepsis by performing in vitro, ex vivo, and in vivo assays. First, we demonstrated that the ACD domain, present exclusively in this toxin variant, effectively has an actin-cross-linking activity. Second, we determined that the whole toxin caused death of human endotheliocytes and monocytes by lysis and apo…
Long Non-coding Antisense RNA TNRC6C-AS1 Is Activated in Papillary Thyroid Cancer and Promotes Cancer Progression by Suppressing TNRC6C Expression
2018
Context: Evidences have shown the important role of long non-coding antisense RNAs in regulating its cognate sense gene in cancer biology. Objective: Investigate the regulatory role of a long non-coding antisense RNA TNRC6C-AS1 on its sense partner TNRC6C, and their effects on the aggressiveness and iodine-uptake ability of papillary thyroid cancer (PTC). Design: TNRC6C-AS1 was identified as the target long non-coding RNA in PTC by using microarray analysis and computational analysis. In vitro gain/loss-of-function experiments were performed to investigate the effects of TNRC6C-AS1 and TNRC6C on proliferation, apoptosis, migration, invasion and iodine-uptake ability of TPC1 cells. Expressio…