NF–KB

Chronic inflammation induces Barrett's Esophagus (BE) which can advance to esophageal adenocarcinoma. Elevated levels of interleukin (IL)-1b, IL-6 and IL-8 together with activated nuclear factor-kappaB (NF-κB), have been identified as important mediators of tumorigenesis. The inflammatory milieu apart from cancer cells and infiltrating immune cells contains myofibroblasts (MFs) that express aSMA and Vimentin. As we observed that increased NF-κB activation and inflammation correlates with increased MF recruitment and an accelerated phenotype we here analyze the role of NF-κB in MF during esophageal carcinogenesis in our L2-IL-1B mouse model...

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a monomeric glycoprotein that has been implicated in the tumor growth and progression of different types of cancer. GM-CSF is produced by various non-immune cells including MDA-MB-231 in response to various stimuli. However, the role of lipopolysaccharide (LPS) in the regulation of GM-CSF in MDA-MB-231 breast cancer cells so far remains unclear. Herein, we asked whether LPS could induce GM-CSF production in MDA-MB-231 cells, and if so, which signaling pathway was involved...

Castanea sativa cultivation has been present in Mediterranean regions since ancient times. In order to promote a circular economy, it is of great importance to valorize chestnut groves' by-products. In this study, leaves and spiny burs from twenty-four Castanea trees were analyzed by 1 H NMR metabolomics to provide an overview of their phytochemical profile. The Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) performed on these data allowed us to distinguish 'Marrone' from 'Castagna', since the latter were generally more enriched with secondary metabolites, in particular, flavonoids (astragalin, isorhamnetin glucoside, and myricitrin) were dominant...

Background and Objective: This study was aimed to elucidate the molecular mechanism of Momordica charantia (MCh) , along with a standard drug prednisolone, in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS). Methods: After the induction of the experimental colitis, the animals were treated with MCh (4 g/kg/day) for 14 consecutive days by intragastric gavage. The colonic tissue expression levels of C-C motif chemokine ligand 17 (CCL-17), interleukin (IL)-1β, IL-6, IL-23, interferon-γ (IFN-γ), nuclear factor kappa B (NF-kB), and tumor necrosis factor-α (TNF-α), were determined at both mRNA and protein levels to estimate the effect of MCh ...

The small molecule gibberellin JRA-003 was identified as an inhibitor of the NF-kB (nuclear kappa-light-chain-enhancer of activated B cells) pathway. Here we find that JRA-003 binds to and significantly inhibits the nuclear translocation of pathway-activating kinases IKKα (IκB kinase alpha) and IKKβ (IκB kinase beta). Analogs of JRA-003 were synthesized and NF-κB-inhibiting gibberellins were found to be cytotoxic in cancer-derived cell lines (HS 578T, HCC 1599, RC-K8, Sud-HL4, CA 46, and NCIH 4466). Not only was JRA-003 identified as the most potent synthetic gibberellin against cancer-derived cell lines, it displayed no cytotoxicity in cells derived from noncancerous sources (HEK 293T, HS 578BST, HS 888Lu, HS 895Sk, HUVEC)...

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia. Proteins in plant sources that enable the maintenance of the glycemic profile may be of interest in the context of T2DM. However, their mechanisms of action are unclear, unlike other bioactive compounds. This systematic review identified and described the mechanisms of action of isolated and purified proteins and peptides extracted from vegetables on the reduction of blood glucose in T2DM in experimental studies. The research was done in PubMed, ScienceDirect, Scopus, Web of Science, Embase and Virtual Health Library (VHL) databases in March 2019...

HOPS/Tmub1 is a ubiquitously expressed transmembrane ubiquitin-like protein that shuttles between nucleus and cytoplasm during cell cycle progression. HOPS causes cell cycle arrest in G0 /G1 phase, an event associated to stabilization of p19Arf , an important tumor suppressor protein. Moreover, HOPS plays an important role in driving centrosomal assembly and maintenance, mitotic spindle proper organization, and ultimately a correct cell division. Recently, HOPS has been described as an important regulator of p53, which acts as modifier, stabilizing p53 half-life and playing a key role in p53 mediating apoptosis after DNA damage...

Cardiomyocyte differentiation is a multi-step process which involves a number of signalling pathways. microRNAs exhibit regulatory functions in various diseases and are involved in the signalling pathways in multiple physiological processes, but the specific functions of particular mRNAs is often not fully understood. of an example of this is that the role of miR-590-3p in the differentiation of cardiomyocytes remains unclear. In the current study, RT-qPCR was used to determine the expression of miR-590-3p in cardiomyocytes differentiated from the embryonic carcinoma cell line P19CL6...

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Silica nanoparticles (SiO2 NPs) are extensively applied in various field, which increased their health risks to humans. SiO2 NPs were reported to enter into blood through inhalation and meanwhile, the potential use of SiO2 NPs as drug carriers in vivo allows them to present in blood circulation to induce inflammation of vascular endothelial cells which can be closely related with cardiovascular diseases, whilst the intrinsic mechanism has not been well understood. In this study, we found a regulation of signal axis induced by amorphous SiO2 NPs that triggers pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs)...

Health disparity related to race/ethnicity has been cited as "the most serious and shameful health care issue of our time"(Peterson et al., 2018). A portion of the now recognized disproportionate impact of the COVID-19 pandemic among Black, Indigenous and People of Color (BIPOC) communities is attributable to social determinants such as socioeconomic status (SES), physical living situation, health care access, and the psychosocial factors associated with socioenvironmental circumstances such as bias, victimization, trauma and toxic stress as well as structural factors that reduce the capacity to practice physical distancing (Agurs-Collins et al...

Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) in which inflammation plays a key pathological role. Recent evidences showed that systemic inflammation induces increasing cell infiltration within meninges and perivascular spaces in the brain parenchyma, triggering resident microglial and astrocytic activation. The anti-inflammatory enzyme A20, also named TNF associated protein 3 (TNFAIP3), is considered a central gatekeeper in inflammation and peripheral immune system regulation through the inhibition of NF-kB...

The β2-Adrenergic receptor (β2-AR) is a G protein-coupled receptor (GPCR), involved in the development of many cancers, among which HNSCC. In this contest, β2-AR signaling interacts with different pathways, such as PI3K and MAPK, commonly activated by TK receptors. For this reason, TK blockade is one of the most adopted therapeutic strategies in HNSCC patients. In our study we investigated the effects of the β2-AR blocking in HNSCC cell lines, using the selective inhibitor ICI118,551 (ICI), in combination with the MAPK inhibitor U0126...

The roles of HOX transcription factors as oncogenes and tumor suppressor genes, and the NF-KB pathway in chronic inflammation, both leading to cancer are well-established. HOX transcription factors are members of an evolutionarily conserved family of proteins required for anteroposterior body axis patterning during embryonic development, and are often dysregulated in cancer. The NF-KB pathway aids inflammation and immunity but it is also important during embryonic development. It is frequently activated in both solid and hematological malignancies...

Chronic stress is linked to liver injury by increasing intestinal permeability to lipopolysaccharide (LPS), which in turn can result in systemic and liver inflammation and damage. Beneficial effect of honey in the prevention of liver injury has been shown in previous studies, but mechanisms underlying are still less known. Here, we examined the therapeutic impacts of honey on intestinal nuclear factor-κB (NF-κB; an important regulator of stress-induced immune and inflammatory responses) and ileal tight junction (TJ) proteins of claudin-1 and ZO-1, serum LPS, liver inflammation and oxidative markers of malondialdehyde (MDA), nitric oxide (NO), (erythroid-derived 2)-like 2 (Nrf2), tumor necrosis factor (TNF)-α and total antioxidant capacity (TAC) following chronic unpredictable mild stress (CUMS) using Western blotting, ELISA kit and spectrophotometry...

An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in tumor development and progression. However, their involvement in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Epigenetic regulation is one major mechanism utilized by cancer cells to control lncRNA expression. We identified that lncRNA VENTXP1 was epigenetically silenced in multiple cancer types, and its lower expression was correlated with poorer survival in HNSCC patients. Through in silico analysis and experimental validation, we identified miR-205-5p and its direct interacting partner of VENTXP1, which regulates HNSCC cell proliferation and tumorigenicity...

3-Deazadenosine (3-DA) is a general methylation inhibitor that depletes S-adenosylmethionine, a methyl donor, by blocking S-adenosylhomocysteine ​​hydrolase (SAHH). In this study, we investigated the inhibitory activity and molecular mechanisms of 3-DA in inflammatory responses. 3-DA suppressed the secretion of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2 ) in lipopolysaccharide-treated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated U937 cells. It also reduced mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β (IL-1 β), and IL-6, indicating that 3-DA has anti-inflammatory properties in murine and human macrophages...

Obesity is associated with elevated levels of TNF-α and proinflammatory CD11c monocytes/macrophages. TNF-α mediated dysregulation in the plasticity of monocytes/macrophages is concomitant with pathogenesis of several inflammatory diseases, including metabolic syndrome, but the underlying mechanisms are incompletely understood. Since neutral sphingomyelinase-2 (nSMase2: SMPD3) is a key enzyme for ceramide production involved in inflammation, we investigated whether nSMase2 contributed to the inflammatory changes in the monocytes/macrophages induced by TNF-α...

Cyclin-dependent kinases (CDKs) belong to the serine/threonine kinase family, and their unique interactions with a variety of cyclin complexes influence its catalytic activity to ensure unimpaired cell cycle progression. In addition to their cell cycle regulatory roles, it is becoming increasingly clear that the CDKs can have multiple functional roles like transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions, and in spermatogenesis. Further in addition, recent reports suggest that CDKs have a remarkable regulatory role in influencing the pro-inflammatory functions of various cytokines during the clinical inflammatory responses...

PD-1/PD-L1 immune checkpoint blockade therapy has been widely used for the clinical treatment of cancer. However, recent clinical trials have shown that only a small proportion of cancer patients respond to PD1/PD-L1 immunotherapy. The tumor immune microenvironment plays an important regulatory role in PD1/PD-L1 immunotherapy. Macrophages are one of the most important immune cells in the tumor immune microenvironment. In this study, we found a high correlation between macrophage infiltration and PD-L1 expression in gastric cancer (GC) specimens...