NF-KB Transcriptional regulation

Inflammation, extracellular matrix metabolic dysfunction, and oxidative stress are key pathogenic characteristics of intervertebral disk degeneration (IVDD), a major pathogenic cause of low back pain. Esculetin possesses anti-injury, anti-inflammation, and antinociceptive properties. This study aimed to explore its role in IVDD. In this research, esculetin exhibited little cytotoxicity to human nucleus pulposus cells (NPCs). Moreover, esculetin increased cell viability under IL-1β stimulation but attenuated IL-1β-induced cell apoptosis and caspase-3 activity...

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model...

In the early 1990's a group of unrelated genes were identified from the sites of recurring translocations in B-cell lymphomas. Despite sharing the nomenclature 'Bcl', and an association with blood-borne cancer, these genes have unrelated functions. Of these genes, BCL2 is best known as a key cancer target involved in the regulation of caspases and other cell viability mechanisms. BCL3 on the other hand was originally identified as a non-canonical regulator of NF-kB transcription factor pathways - a signaling mechanism associated with important cell outcomes including many of the hallmarks of cancer...

Intracerebral haemorrhage (ICH) is a lethal cerebrovascular disorder with a high mortality and morbidity. Although it is a major public health problem, there is no effective treatment for ICH. After ICH, the primary and secondary mechanisms are mentioned when discussing brain injury. The transcription factor, nuclear factor-kappa B (NF-kB), is an important regulator of inflammatory responses. The role of platelet factor 4 (PF4) in ICH is unclear. To study the effect of PF4 on inflammatory response of rats in ICH, a rat model of striatum ICH was established by injecting autologous blood from the autogenous femoral artery into the right striatum of rats...

Hematopoietic stem and progenitor cells generate all the lineages of blood cells throughout the lifespan of vertebrates. The emergence of hematopoietic stem and progenitor cells is finely tuned by a variety of signaling pathways. Previous studies have revealed the roles of pattern-recognition receptors such as Toll-like receptors and RIG-I-like receptors in hematopoiesis. In this study, we find that Nlrc3, a nucleotide-binding domain leucine-rich repeat containing family gene, is highly expressed in hematopoietic differentiation stages in vivo and vitro and is required in hematopoiesis in zebrafish...

Despite the importance of the endothelium in the regulation of the blood brain barrier (BBB) in aging and neurodegenerative disease, difficulties in extracting endothelial cell (EC) nuclei have limited analysis of these cells. In addition, nearly all Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration (FTD), and a large portion of Alzheimer's Disease (AD) exhibit neuronal TDP-43 aggregation, leading to loss of nuclear function, but whether TDP-43 is similarly altered in human BBB ECs is unknown...

Throughout human history, the utilization of medicinal herbs has been recognized as a crucial defense against various ailments, including cancer. Natural products with potential anticancer properties, capable of inducing apoptosis in cancer cells, have garnered substantial attention. One such agent under investigation is guggulsterone (GS), a phytosterol derived from the gum resin of the Commiphora mukul tree. This review aims to provide a comprehensive summary of recent studies elucidating the anticancer molecular mechanisms and molecular targets of GS, guiding future research and potential applications as an adjuvant drug in cancer therapy...

The PBAF chromatin remodeling complex regulates chromatin state and gene transcription in higher eukaryotes. In this work, we studied the role of PBAF in the regulation of NF-κB-and JAK/STAT-dependent activation of inflammatory genes. We performed knockdown of specific module subunit BAF200, which resulted in destruction of the entire PBAF specific module and changed the level of the genes transcription of both pathways. PBAF can be both an activator and a repressor of inflammatory genes. Thus, PBAF is an important regulator of inflammatory gene expression...

The major innate immune responder to the DNA of pathogens is the cyclic GMP-AMP (cGAMP) synthase (cGAS) - stimulator of interferon genes (STING) pathway. Most prominently, the outcome of cGAS signalling is the activation of inflammatory transcription through interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB). In addition, the cGAS-STING pathway can lead to the direct modulation of cellular processes independently of transcription, such as activation of autophagy. Under unperturbed conditions, several mechanisms are in place to prevent the activation of cGAS by self-DNA, chiefly its sequestration on chromatin, which interferes with binding to stimulatory DNA...

Ref-1/APE1 (Redox Effector/Apurinic Endonuclease 1) is a multifunctional enzyme that serves as a redox factor for several transcription factors (TFs), e.g., NF-kB, HIF-1α, which in an oxidized state fail to bind DNA. Conversion of these TFs to a reduced state serves to regulate various biological responses such as cell growth, inflammation, and cellular metabolism. The redox activity involves a thiol exchange reaction for which Cys65 (C65) serves as the nucleophile. Using CRISPR editing in human pancreatic ductal adenocarcinoma (PDAC) cells, we changed C65 to Ala (C65A) in Ref-1 to evaluate alteration of Ref-1 redox dynamics as well as chronic loss of Ref-1 redox activity on cell signaling pathways, specifically those regulated by NF-kB and HIF-1α...

Reducing inflammation by diet is a major goal for prevention or lowering symptoms of a variety of diseases, such as auto-immune reactions and cancers. Natural polysaccharides are increasingly gaining attention due to their potential immunomodulating capacity. Structures of those molecules are highly important for their effects on the innate immune system, cytokine production and secretion, and enzymes in immune cells. Such polysaccharides include β-glucans, pectins, fucoidans, and fructans. To better understand the potential of these immunomodulatory molecules, it is crucial to enhance dedicated research in the area...

Bisphenol AF (BPAF) is extensively used in industrial production as an emerging substitute for the earlier-used bisphenol A (BPA). Studies have found that BPAF had stronger estrogenic activities than BPA. However, the effects of BPAF on the luteal function of pregnancy and its possible mechanisms are largely unknown. In this study, pregnant mice were orally administered 3.0 and 30 mg/kg/day of BPAF from gestational day (GD) 1 to 8, and samples were collected on GD 8 and GD 19. Results showed that maternal exposure to BPAF impaired embryo implantation and reduced ovarian weight, and interfered with steroid hormone secretion, and decreased the numbers and areas of corpus luteum...

Osteoporotic bone defect has become clinic challenge due to its morbid bone microenvironment. Overactive bone resorption and limited bone formation lead to unstable combination between bone tissue and scaffolds. Electrospinning has been widely used in guide tissue membrane, but its barrier property results in limited application. In order to optimize the structure and add anti-bone resorption function of electrospinning fibers, we exploited the application of short fibers generated by homogenization at osteoporotic tibial bone defect...

Probiotics are live microorganisms that yield health benefits when consumed, generally by improving or restoring the intestinal flora (microbiota) as part of the muco-microbiotic layer of the bowel. In this work, mice were fed with ethanol alone or in combination with the probiotic Lactobacillus fermentum ( L. fermentum ) for 12 weeks. The modulation of the NF-κB signaling pathway with the induction of Hsp60, Hsp90, and IkB-α by the probiotic occurred in the jejunum. L. fermentum inhibited IL-6 expression and downregulated TNF-α transcription...

OBJECTIVE: Aging is associated with increased pro-inflammatory gene expression and systemic inflammation, and psychosocial stress may accelerate these changes. Mindfulness interventions show promise for reducing psychosocial stress and extending healthspan. Inflammatory pathways may play a role. In a sample of lonely older adults, we tested whether mindfulness training reduces proinflammatory gene expression and protein markers of systemic inflammation. METHODS: Lonely older adults (65-85 years; N = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or matched Health Enhancement Program (HEP)...

Introduction Dopamine is an important neuroregulatory hormone and is secreted during exercise. Its role in physiological regulation is not fully uncovered. Recent studies showed that it suppresses inflammation. Colon cancer is one of the most predominant cancers in the population and is influenced by prolonged inflammation. The anti-inflammatory effect of dopamine using the colon cancer model was analyzed in KB cells. Methods KB cells were cultured using Dulbecco's Modified Eagle Medium   and Inhibitory Concentration- 50 (IC50 ) was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay...

BACKGROUND: The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl...

Behect's disease is a chronic vasculitis characterized by complex multi-organ immune aberrations. However, a comprehensive understanding of the gene-regulatory profile of peripheral autoimmunity and the diverse immune responses across distinct cell types in Behcet's disease (BD) is still lacking. Here, we present a multi-omic single-cell study of 424,817 cells in BD patients and non-BD individuals. This study maps chromatin accessibility and gene expression in the same biological samples, unraveling vast cellular heterogeneity...

The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape we conducted a gain of function, genome-wide CRISPR activation screen with influenza A virus. We identified both appreciated and novel antiviral genes, including JADE3 a protein involved in directing the histone acetyltransferase HBO1 complex to modify chromatin and regulate transcription. JADE3 is both necessary and sufficient to restrict influenza A virus infection...

BACKGROUND: The study aimed to observe molecular signaling, including reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm), to evaluate the alteration of gene expression by low-level laser therapy (LLLT) and the correlation between its mechanisms and the NF-kB pathway in cells involved in orthodontic tooth movement. METHODS: Osteoblast-like cells (MG63), immortalized periodontal ligament cells (iPDL), and M1 macrophage-like cells were irradiated by 980-nm LLLT with energy densities of 1 and 10 J/cm2 ΔΨm and intracellular ROS were monitored using fluorescent probes...