toll like receptors and lymphoma

Background: MicroRNA-216a-5p (miR-216a-5p) mediates inflammatory responses and neuronal injury to participate in the pathology of spinal cord injury (SCI). This study intended to explore the engagement of bone marrow mesenchymal stem cell exosomes (BMSC-Exo)-derived miR-216a-5p in locomotor performance, neuronal injury, and microglia-mediated inflammation in SCI rats. Methods: Rat BMSC or BMSC-Exo was injected into SCI rats. GW4869 treatment was adopted to suppress the exosome secretion from BMSC. Subsequently, miR-216a-5p-overexpressed BMSC-Exo (BMSC-miR-Exo) or negative-control-overexpressed BMSC-Exo (BMSC-NC-Exo) were injected into SCI rats...

Cutaneous T-cell lymphomas (CTCL) encompass a group of diseases characterized by the presence of malignant clonal CD4+ T lymphocytes in the skin. Mycosis fungoides (MF) is the most prevalent form of CTCL, accounting for approximately 60% of cutaneous T-cell lymphomas and 50% of all primary cutaneous lymphomas. Despite ongoing research, the precise pathogenesis of MF remains incompletely understood. Toll-like receptors (TLRs) have the ability to specifically recognize ligands, subsequently induce the expression of diverse genes and activate innate immunity within the cell...

Immune checkpoint blockade (ICB) therapy has significantly benefited patients with several types of solid tumors and some lymphomas. However, many of the treated patients do not have durable clinical response. It has been demonstrated that rescuing exhausted CD8 + T cells is required for ICB-mediated antitumor effects. We recently developed an immunostimulatory strategy based on silencing STAT3 while stimulating immune responses by CpG, ligand for Toll-like receptor 9 (TLR9). The CpG-small interfering RNA (siRNA) conjugates efficiently enter immune cells, silencing STAT3 and activating innate immunity to enhance T-cell mediated antitumor immune responses...

UNLABELLED: Patients with diffuse large cell lymphoma who have an adequate vitamin D supply derive significantly more benefit from immuno-chemotherapy with rituximab than patients with vitamin D deficiency; this is especially true for female patients. We have already been able to show that vitamin D increases the antibody-dependent cytotoxicity (ADCC) of NK cells in a sex-dependent manner, but it is unclear how vitamin D makes NK cells more efficient. METHODS: Healthy individuals with vitamin D deficiency were supplemented with vitamin D to sufficient levels...

MYD88 is the key signaling adaptor-protein for Toll-like and interleukin-1 receptors. A somatic L265P mutation within the Toll/interleukin-1 receptor (TIR) domain of MYD88 is found in 90% of Waldenström macroglobulinemia cases and in a significant subset of diffuse large B-cell lymphomas. MYD88-L265P strongly promotes NF-κB pathway activation, JAK-STAT signaling and lymphoma cell survival. Previous studies have identified other residues of the TIR-domain crucially involved in NF-κB activation, including serine 257 (S257), indicating a potentially important physiological role in the regulation of MYD88 activation...

Decoy-oligodeoxynucleotides (D-ODNs) can target undruggable transcription factors, such as STAT3. However, challenges in D-ODN delivery and potency hampered their translation. To overcome these limitations, we conjugated STAT3-specific D-ODN to thalidomide (Tha), a known ligand to cereblon (CRBN, a component of E3 ubiquitin ligase) to generate a proteolysis-targeting chimera (STAT3D PROTAC ). STAT3D PROTAC downregulated STAT3, but not STAT1 or STAT5, in target cells. Computational modeling of the STAT3D PROTAC ternary complex predicted two surface lysines on STAT3, K601 and K626 as potential ubiquitination sites for the PROTAC bound E3 ligase...

The use of functional foods and their bioactive components is receiving increasing attention as a complementary and alternative therapy for chronic ulcerative colitis (UC). This study explored the protective effect and mechanisms of Eckol, a seaweed-derived bioactive phlorotannin, on the dextran sodium sulfate (DSS)-induced chronic UC in mice. Eckol (0.5-1.0 mg/kg) reduced DSS-enhanced disease activity indexes, and alleviated the shortening of colon length and colonic tissue damage in chronic UC mice. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly decreased, and the level of anti-inflammatory IL-10 was enhanced in the serum and colonic tissues collected from Eckol-treated mice compared with the DSS controls...

Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease comprised of at least 5 recognized molecular subtypes. Cluster 5/ MCD tumors frequently exhibit concurrent alterations of the Toll-like receptor (TLR) and B-cell receptor (BCR) pathway members, MYD88L265P and CD79B, and have a less favorable prognosis. In normal B cells, the synergy between TLR and BCR signaling pathways integrates innate and adaptive immune responses and augments downstream NF-kB activation. Additionally, physiologic TLR9 pathway engagement, via MYD88, PYK2 and DOCK8, increases proximal BCR signaling in normal murine B cells...

PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare central nervous system (CNS) malignancy, which represents a heterogenous group of tumors. Among PCNSL, diffuse large B-cell lymphoma of the CNS (CNS-DLBCL) represents the most common tumor type. Multiomics studies have recently revealed the complex genomic landscape of these rare diseases. These findings lead to a potential new molecular and epigenetic classification. RECENT FINDINGS: Our review is focused on CNS-DLBCL in immunocompetent patients...

Toxic effects of abamectin on non-target aquatic organisms have been well documented due to its extensive use in both agricultural and aquacultural areas. However, knowledge of the abamectin induced cytotoxicity in crustacean hepatopancreas is still incomplete. In this study, we investigated the cytotoxic effects of abamectin on hepatopancreas cells of Chinese mitten crab, Eriocheir sinensis by an in vitro assay. The results showed that abamectin inhibited cell viability with elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels in a dose-dependent manner...

Kaposi's sarcoma-associated herpesvirus (KSHV) and the Epstein-Barr virus (EBV) are double-stranded DNA oncogenic gammaherpesviruses. These two viruses are associated with multiple human malignancies, including both B and T cell lymphomas, as well as epithelial- and endothelial-derived cancers. KSHV and EBV establish a life-long latent infection in the human host with intermittent periods of lytic replication. Infection with these viruses induce the expression of both viral and host RNA transcripts and activates several RNA sensors including RIG-I-like receptors (RLRs), Toll-like receptors (TLRs), protein kinase R (PKR) and adenosine deaminases acting on RNA (ADAR1)...

Candida albicans is a pathogenic yeast recently associated with diverse diseases in aquaculture. The present study investigated the efficacy of chitosan nanogel (CNG) in ameliorating effects of C. albicans on Nile tilapia (Oreochromis niloticus). Fish were randomly distributed into four groups (control, waterborne CNG at 75 μg/L, intraperitoneally challenged with C. albicans (1.8 × 107 CFU/mL), and waterborne CNG at 75 μg/L + C. albicans at 1...

Primary central nervous system lymphoma (PCNSL) is a diffuse large B cell lymphoma in which the brain, spinal cord, leptomeninges and/or eyes are exclusive sites of disease. Pathophysiology is incompletely understood, although a central role seems to comprise immunoglobulins binding to self-proteins expressed in the central nervous system (CNS) and alterations of genes involved in B cell receptor, Toll-like receptor and NF-κB signalling. Other factors such as T cells, macrophages or microglia, endothelial cells, chemokines, and interleukins, probably also have important roles...

Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity per se upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model...

Inflammasomes are cytosolic signaling hubs that promote the inflammatory response (i.e. an immune reaction to counteract threats in physiological conditions). Their potential role in lymphomagenesis remains to be elucidated. Depending on the context, innate immune cells, such as macrophages, may induce inflammation that contributes to the anti-tumor function; however, if uncontrolled, inflammation can promote cancer development. Here, we exploited bioinformatic tools, TCGA data, and tumor tissue samples from patients with diffuse large B-cell lymphoma (DLBCL), one of the most frequent non-Hodgkin lymphomas of B-cell origin, to investigate the distribution of the different immune cell subpopulations in DLBCL samples in order to characterize the immune landscape of their microenvironment...

B-cell receptor (BCR) signaling is essential for the diffuse large B-cell lymphoma (DLBCL) subtype that originates from activated B-cells (ABC). ABC-DLBCL cells are sensitive to Bruton tyrosine kinase intervention. However, relapsed or refractory ABC-DLBCL patients had overall response rates of 33-37% for Bruton tyrosine kinase inhibitors, suggesting the evaluation of combination-based treatment for improved efficacy. We investigated the efficacy and mechanism of bromodomain and extra-terminal motif (BET) inhibitor AZD5153 combined with the Bruton tyrosine kinase inhibitor acalabrutinib in ABC-DLBCL preclinical models...

BACKGROUND: Exposure to chronic psychological stress is a risk factor for metabolic cardiovascular disease. Given the important role of lysosomal CTSS (cathepsin S) in human pathobiology, we examined the role of CTSS in stress-related thrombosis, focusing on inflammation, oxidative stress, and apoptosis. METHODS: Six-week-old wild-type mice (CTSS +/+ ) and CTSS-deficient mice (CTSS-/- ) randomly assigned to nonstress and 2-week immobilization stress groups underwent iron chloride3 (FeCl3 )-induced carotid thrombosis surgery for morphological and biochemical studies...

During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family and translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 trigger oncogenic NF-κB signaling independent of receptor stimulation, which leads to the development of B-cell malignancies. However, the exact molecular mechanisms and downstream signaling targets remain unresolved...

Spleen is an ideal site for initiating and amplifying antigen-specific immune response. However, spleen-selective antigen delivery has limited tumor therapeutic efficacy owing to an inadequate cytotoxic T-cell immune response. In this study, we designed a spleen-selective mRNA vaccine that delivered unmodified mRNA and Toll-like Receptor (TLR) agonists to the spleen after systemic administration, resulting in a sufficient and persistent antitumor cellular immune response with potent tumor immunotherapeutic efficacy...

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance...